Skip to main content
SpringerLink
Log in

Modern Drug Discovery and Development in the Area of Leishmaniasis

  • Chapter
  • First Online:
Drug Discovery and Drug Development

Abstract

Leishmaniasis is vector borne disease, caused by various species of protozoan parasite belonging to the genus Leishmania. Worldwide, there are more than 12 million reported cases of leishmaniasis and about 350 million people are at risk in at least 98 developing countries in Africa, South-East Asia and the Americas. The three clinical manifestations are cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL) and fatal visceral leishmaniasis (VL). India together with Brazil, Sudan, Bangladesh and Nepal, carries 90% of the global burden of VL. In the absence of any vaccine, chemotherapy is the only way to tackle the control of this disease. Unfortunately, the clinically approved drugs are costly, toxic, require longer periods of administration and have the problem of resistance. The leishmaniasis elimination program, launched by WHO in 2005, had the projected target of eliminating the disease in India by 2017; however, until date, target could not be achieved. This underscores the need for development of new antileishmanial agent that is administered orally. Research efforts to identify new chemical entities, using both phenotypic and target-based screening led to the identification of several scaffolds, eliciting antileishmanial activity against intracellular stage of parasite mostly under in vitro condition. However, only a few of them are under developmental stage, resulting in inefficient drug pipeline. Simultaneously, there is lack of interest from Pharma-industry to support discovery of new medicines for leishmaniasis due to limited business, it would generate. Therefore, responsibility to discover and develop new chemotherapy lies on academia and philanthropic agencies including Drugs for Neglected Diseases initiative (DNDi). Recently, with increasing societal pressure to share the responsibility, a few pharma companies are collaborating with WHO and National control agencies to assist control programs on neglected diseases specially in endemic areas. In one such effort, Gilead Biosciences is donating liposomized AmphotericinB to support VL elimination program in endemic countries of South-East Asia including India. This chapter would assimilate the status of visceral leishmaniasis in Indian context and the ongoing drug discovery efforts being pursued to treat it.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Afrin F, Chouhan G, Islamuddin M, Want MY, Ozbak HA, Hemeg HA (2019) Cinnamomum cassia exhibits antileishmanial activity against Leishmania donovani infection in vitro and in vivo. PLoS Negl Trop Dis 13:e0007227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alcântara LM, Ferreira TCS, Gadelha FR, Miguel DC (2018) Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. Int J Parasitol Drugs Drug Resist 8:430–439

    Article  PubMed  PubMed Central  Google Scholar 

  • Alvar J, Aparicio P, Aseffa A et al (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21:334–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alvar J, Vélez ID, Bern C et al (2012) Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7:e35671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alves F, Bilbe G, Blesson S et al (2018) Recent development of visceral leishmaniasis treatments: successes, pitfalls, and perspectives. Clin Microbiol Rev 31:e00048–e00018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrade-Narvaez FJ, Loría-Cervera EN, Sosa-Bibiano EI, Van Wynsberghe NR (2016) Asymptomatic infection with American cutaneous leishmaniasis: epidemiological and immunological studies. Mem Inst Oswaldo Cruz 111:599–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrews KT, Fisher G, Skinner-Adams TS (2014) Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist 4:95–111

    Article  PubMed  PubMed Central  Google Scholar 

  • Arshia AF, Ghouri N, Kanwal KKM, Perveen S, Choudhary MI (2018) Synthesis of 4-substituted ethers of benzophenone and their antileishmanial activities. R Soc OpenSci 5:171771

    Article  CAS  Google Scholar 

  • Ashburn TT, Thor KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 3:673–683

    Article  CAS  PubMed  Google Scholar 

  • Asthana S, Jaiswal AK, Gupta PK, Dube A, Chourasia MK (2015) Th-1 biased immunomodulation and synergistic antileishmanial activity of stable cationic lipid–polymer hybrid nanoparticle: biodistribution and toxicity assessment of encapsulated amphotericin B. Eur J Pharm Biopharm 89:62–73

    Article  CAS  PubMed  Google Scholar 

  • Atta KFM, Ibrahim TM, Farahat OOM et al (2017) Synthesis, modelling and biological evaluation of hybrids from pyrazolo[1,5-c]pyrimidine as antileishmanial agents. Future Med Chem 9:1913–1929

    Article  CAS  PubMed  Google Scholar 

  • Aubé J (2012) Drug repurposing and the medicinal chemist. ACS Med Chem Lett 3:442–444

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bora D (1999) Epidemiology of visceral leishmaniasis in India. Natl Med J India 12:62–68

    CAS  PubMed  Google Scholar 

  • Bruni N, Stella B, Giraudo L, Della PC, Gastaldi D, Dosio F (2017) Nanostructured delivery systems with improved leishmanicidal activity: a critical review. Int J Nanomedicine 12:5289–5311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burza S, Mahajan R, Sanz MG et al (2014) HIV and visceral leishmaniasis coinfection in Bihar, India: an under-recognized and under-diagnosed threat against elimination. Clin Infect Dis 59:552–555

    Article  PubMed  Google Scholar 

  • Burza S, Croft SL, Boelaert M (2018) Leishmaniasis. Lancet 392:951–970

    Article  PubMed  Google Scholar 

  • Chakravarty J, Sundar S (2010) Drug resistance in leishmaniasis. J Global Infect Dis 2:167

    Article  Google Scholar 

  • Chandrasekar R, Debnath S, Sivagami B, Jayasree P, Niranjan BM (2018) Therapeutic efficacy of flavonoids and terpenoids an ongoing herbal therapy in the treatment of leishmaniasis. Nat Prod Ind J 14:124

    CAS  Google Scholar 

  • Chauhan SS, Pandey S, Shivahare R et al (2015) Novel β-carboline–quinazolinone hybrid as an inhibitor of Leishmania donovani trypanothione reductase: synthesis, molecular docking and bioevaluation. Med Chem Commun 6:351–356

    Article  CAS  Google Scholar 

  • ClinicalTrials.gov (2013) Trial to determine efficacy of fexinidazole in visceral leihmaniasispatients in Sudan. http://clinicaltrials.gov/show/NCT01980199. Accessed 12 Nov 2013

  • Correia D, Macedo VO, Carvalho EM et al (1996) Comparative study of meglumine antimoniate, pentamidine isethionate and aminosidinesulfate in the treatment of primary skin lesions caused by Leishmania (Viannia) braziliensis. Rev Soc Bras Med Trop 29:447–453

    Article  CAS  PubMed  Google Scholar 

  • Cota GF, de Sousa MR, de Mendonca AL, Patrocinio A, Assunção LS, de Faria SR, Rabello A (2014) Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil. PLoS Negl Trop Dis 8:e2816

    Article  PubMed  PubMed Central  Google Scholar 

  • Croft SL, Seifert K, Duchêne M (2003) Antiprotozoal activities of phospholipid analogues. Mol Biochem Parasitol 126:165–172

    Article  CAS  PubMed  Google Scholar 

  • Dar AA, Shadab M, Khan S, Ali N, Khan AT (2016) One-pot synthesis and evaluation of antileishmanial activities of functionalized S-Alkyl/Aryl benzothiazole-2-carbothioate scaffold. J Organomet Chem 81:3149–3160

    Article  CAS  Google Scholar 

  • Dea-Ayuela P, Bilbao-Ramos MA, Bolás-Fernández F, González-Cardenete MA (2016) Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives. Eur J Med Chem 121:445–450

    Article  CAS  PubMed  Google Scholar 

  • Desjeux P, Ghosh RS, Dhalaria P, Strub-Wourgaft N, Zijlstra EE (2013) Report of the post kala-azar dermal leishmaniasis (PKDL) consortium meeting, New Delhi, India, 27–29 June, 2012. Parasit Vectors 6:196

    Article  PubMed  PubMed Central  Google Scholar 

  • Diro E, Lynen L, Mohammed R, Boelaert M, Hailu A, van Griensven J (2014) High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia. PLoS Negl Trop Dis 8:e2875

    Article  PubMed  PubMed Central  Google Scholar 

  • Diro E, Ritmeijer K, Boelaert M et al (2015) Use of pentamidine as secondary prophylaxisto prevent visceral leishmaniasis relapse in HIV infected patients, thefirst twelve months of a prospective cohort study. PLoS Negl Trop Dis 9:e0004087

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DNDI (n.d.) DNDI-5561 – DNDi. https://www.dndi.org/diseases-projects/portfolio/dndi-5561/

  • DNDi (2016) Fexinidazole/miltefosine combination (VL). Available from https://www.dndi.org/diseases-projects/portfolio/completed-projects/fexinidazole-vl/

  • Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ (2012) Miltefosine: a review ofits pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 67:2576–2597

    Article  CAS  PubMed  Google Scholar 

  • Espuelas MS, Legrand P, Campanero MA, Appel M, Chéron M, Gamazo C, Barratt G, Irache JM (2003) Polymeric carriers for amphotericin B: in vitro activity, toxicity and therapeutic efficacy against systemic candidiasis in neutropenic mice. J Antimicrob Chemother 52:419–427

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, Lu Y, Chen X, Tekwani BL, Li XC, Shen Y (2018) Anti-leishmanial and cytotoxic activities of a series of maleimides: synthesis, biological evaluation and structure-activity relationship. Molecules 23:2878

    Article  PubMed Central  CAS  Google Scholar 

  • Félix MB, de Souza ER, de Lima MCA et al (2016) Antileishmanial activity of new thiophene-indole hybrids: design, synthesis, biological and cytotoxic evaluation, and chemometric studies. Bioorg Med Chem 24:3972–3977

    Article  PubMed  CAS  Google Scholar 

  • Ferreira LLG, Andricopulo AD (2018) Chemoinformatics strategies for leishmaniasis drug discovery. Front Pharmacol 9:1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrins L, Pollastri MP (2018) The importance of collaboration between industry, academics, and nonprofits in tropical disease drug discovery. ACS Infect Dis 4:445–448

    Article  CAS  PubMed  Google Scholar 

  • Fersing C, Basmaciyan L, Boudot C et al (2019) Nongenotoxic 3-nitroimidazo[1,2-a]pyridines Are NTR1 substrates that display potent in vitro antileishmanial activity. ACS Med Chem Lett 10:34–39

    Article  CAS  PubMed  Google Scholar 

  • Fonseca-Berzal C, Ibáñez-Escribano A, Vela N et al (2018) Antichagasic, leishmanicidal, and trichomonacidal activity of 2-benzyl-5-nitroindazole-derived amines. ChemMedChem 13:1246–1259

    Article  CAS  PubMed  Google Scholar 

  • de Freitas EO, Leoratti FM, Freire-de-Lima CG, Morrot A, Feijó DF (2016) The contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis. Front Immunol 7:153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Freitas-Junior LH, Chatelain E, Kim HA, Siqueira-Neto JL (2012) Visceral leishmaniasis treatment: what do we have, what do we need and how to deliver it? Int J Parasitol Drugs Drug Resist 2:11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghozlani ME, Bouissane L, Berkani M et al (2019) Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds. Med Chem Commun 10:120–127

    Article  Google Scholar 

  • Government of Nepal - Ministry of Health and Population (2009) Kala-azar elimination program in Nepal. National strategic guideline on kala-azar elimination program in Nepal

    Google Scholar 

  • Guo LS, Working PK (1993) Complexes of amphotericin B and cholesteryl sulfate. J Liposome Res 3:473–490

    Article  CAS  Google Scholar 

  • Gupta S, Yardley V, Vishwakarma P, Shivahare R, Sharma B, Launay D, Martin D, Puri SK (2015) Nitroimidazo-oxazole compound DNDI-VL-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis. J Antimicrob Chemother 70:518–527

    Article  CAS  PubMed  Google Scholar 

  • Handman E (1999) Cell biology of Leishmania. Adv Parasitol 44:1–39

    Article  CAS  PubMed  Google Scholar 

  • Hendrickx S, Beyers J, Mondelaers A, Eberhardt E, Lachaud L, Delputte P, Cos P, Maes L (2016) Evidence of a drug-specific impact of experimentally selected paromomycin and miltefosine resistance on parasite fitness in Leishmania infantum. J Antimicrob Chemother 71:1914–1921

    Article  CAS  PubMed  Google Scholar 

  • Hnik P (2016) Stable formulations for the oral administration of amphotericin B. WO2016112339A1. Chem Abstr 165:169462

    Google Scholar 

  • Jacob RT, Liu Y, Sciotti RJ (2018) Novel oxaborole analogs and uses thereof. WO2018160845A1. Chem Abstr 169:347172

    Google Scholar 

  • Jacomini AP, Silva MJV, Silva RGM et al (2016) Synthesis and evaluation against Leishmania amazonensis of novelpyrazolo[3,4-d]pyridazinone-N-acylhydrazone-(bi)thiophene hybrids. Eur J Med Chem 124:340–349

    Article  CAS  PubMed  Google Scholar 

  • Jain K, Jain NK (2013) Novel therapeutic strategies for treatment of visceral leishmaniasis. Drug Discov Today 18:1272–1281

    Article  CAS  PubMed  Google Scholar 

  • Jameson MB, Rischin D, Pegram M, Gutheil J, Patterson AV, Denny WA, Wilson WR (2010) A nitrogen mustard prodrug activated by both hypoxia andaldo-keto reductase 1C3, in patients with solid tumors. Cancer Chemother Pharmacol 65:791–801

    Article  CAS  PubMed  Google Scholar 

  • Javed I, Hussain SZ, Ullah I et al (2015) Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B. J Mater Chem B 3:8359–8365

    Article  CAS  PubMed  Google Scholar 

  • Jha SN, Singh NK, Jha TK (1991) Changing response to diamidine compounds in cases of kala-azar unresponsive to antimonial. J Assoc Physicians India 39:314–316

    CAS  PubMed  Google Scholar 

  • Jha TK, Sundar S, Thakur CP, Felton JM, Sabin AJ, Horton J (2005) A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. Am J Trop Med Hyg 73:1005–1011

    Article  CAS  PubMed  Google Scholar 

  • Kanwar A, Eduful BJ, Barbeto L et al (2017) Synthesis and activity of a new series of antileishmanial agents. ACS Med Chem Lett 8:797–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khare S, Nagle AS, Biggart A et al (2016) Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 537:229–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khatta SN, Haiba NS, Asal AM, Bekhit AA, Guemei AA, Amer A, El-Faham A (2017) Study of antileishmanial activity of 2-aminobenzoyl amino acid hydrazides and their quinazoline derivatives. Bioorg Med Chem Lett 27:918–921

    Article  CAS  Google Scholar 

  • Khattab SN, Khalil HH, Bekhit AA, El-Rahman MMA, de la Torre BG, El-Faham A, Albericio F (2018) 1,3,5-Triazino peptide derivatives: synthesis, characterization, and preliminary antileishmanial activity. ChemMedChem 13:725–735

    Article  CAS  PubMed  Google Scholar 

  • Kima PE (2014) Leishmania molecules that mediate intracellular pathogenesis. Microbes Infect 16:721–726

    Article  CAS  PubMed  Google Scholar 

  • Klug DM, Gelb MH, Pollastri MP (2016) Repurposing strategies for tropical disease drug discovery. Bioorg Med Chem Lett 26:2569–2576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krause G, Kroeger A (1994) Topical treatment of American cutaneous leishmaniasis with paromomycin and methyl benzethonium chloride: a clinical study under field conditions in Ecuador. Trans R Soc Trop Med Hyg 88:92–94

    Article  CAS  PubMed  Google Scholar 

  • Kumar R, Sahoo GC, Pandey K, Das V, Das P (2016) Development of PLGA-PEG encapsulated miltefosine based drug delivery system against visceral leishmaniasis. Mater Sci Eng C Mater Biol Appl 59:748–753

    Article  CAS  PubMed  Google Scholar 

  • Leañez J, Nuñez J, García-Marchan Y et al (2019) Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis. Exp Parasitol 198:31–38

    Article  PubMed  CAS  Google Scholar 

  • Lindoso JAL, Moreira CHV, Cunha MA, Queiroz IT (2018) Visceral leishmaniasis and HIV coinfection: current perspectives. HIV/AIDS 10:193–201

    CAS  Google Scholar 

  • Mathur P, Samantaray JC, Vajpayee M, Samanta P (2006) Visceral Leishmaniasis/human immunodeficiency virus co-infection in India: the focus of two epidemics. J Med Microbiol 55:919–922

    Article  PubMed  Google Scholar 

  • Mbekeani AJ, Jones RS, Llorens MB et al (2019) Mining for natural product antileishmanials in a fungal extract library. Int J Parasitol Drugs Drug Resist 11:118. https://doi.org/10.1016/j.ijpddr.2019.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGwire BS, Satoskar AR (2013) Leishmaniasis: clinical syndromes and treatment. QJM 107:7–14

    Article  PubMed  PubMed Central  Google Scholar 

  • Melaku Y, Collin SM, Keus K, Gatluak F, Ritmeijer K, Davidson RN (2007) Treatment of kala-azar in southern Sudan using a 17-day regimen of sodium stibogluconate combined with paromomycin: a retrospective comparison with 30-daysodium stibogluconate monotherapy. Am J Trop Med Hyg 77:89–94

    Article  CAS  PubMed  Google Scholar 

  • Mengesha B, Endris M, Takele Y, Mekonnen K, Tadesse T, Feleke A, Diro E (2014) Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study. BMC Res Notes 7:75

    Article  PubMed  PubMed Central  Google Scholar 

  • Mishra KB, Tiwari N, Bose P, Singh R, Rawat AK, Singh SK, Mishra RC, Singh RK, Tiwari VK (2019) Design, synthesis and pharmacological evaluation of noscapine glycoconjugates. Chem Select 4:2644–2648

    CAS  Google Scholar 

  • Molyneux DH, Killick-Kendrick R (1987) Morphology, ultrastructure and life cycles. In: Peters W, Killick-Kendrick R (eds) The leishmaniases in biology and medicine, vol 1. Academic Press, London, pp 121–176

    Google Scholar 

  • Mondal D, Singh SP, Kumar N et al (2009) Visceral leishmaniasis elimination programme in India, Bangladesh, and Nepal: reshaping the case finding/case management strategy. PLoS Negl Trop Dis 3:e355

    Article  PubMed  PubMed Central  Google Scholar 

  • Morizot G, Jouffroy R, Faye A et al (2016) Antimony to cure visceral leishmaniasis unresponsive to liposomal amphotericin B. PLoS Negl Trop Dis 10:e0004304

    Article  PubMed  PubMed Central  Google Scholar 

  • Mowbray CE, Braillard S, Speed W (2015) Novel amino-pyrazole Ureas with potent in vitro and in vivo antileishmanial activity. J Med Chem 58:9615–9624

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay R, Mukherjee, S, Mukherjee B, Naskar K, Mondal D, Decuypere S, Ostyn B, Prajapati VK, Sundar S, Dujardin JC, Roy S. (2011) Characterisation of antimony-resistant Leishmania donovani isolates: Biochemical and biophysical studies and interaction with host cells. Int. J Parasitol. 41:1311–1321

    Google Scholar 

  • Murillo JA, Gil JF, Upegui YA et al (2019) Antileishmanial activity and cytotoxicity of ent-beyerene diterpenoids. Bioorg Med Chem 27:3972–3977

    Article  CAS  Google Scholar 

  • Musa A, Khalil E, Hailu A et al (2012) Sodium stibogluconate (SSG) and paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial. PLoS Negl Trop Dis 6:e1674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagle AS, Khare S, Kumar AB et al (2014) Recent developments in drug discovery for leishmaniasis and human african trypanosomiasis. Chem Rev 114:11305–11347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narayan S, Thakur CP, Bahadur S, Thakur M, Pandey SN, Thakur AK, Mitra DK, Mukherjee PK (2017) Cedrus deodara: in vitro antileishmanial efficacy and immumomodulatory activity. Indian J Med Res 146:780–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nocentini A, Supuran CT, Winum J-Y (2018) Benzoxaborole compounds for therapeutic uses: a patent review (2010-2018). Expert Opin Ther Patent 28:493–504

    Article  CAS  Google Scholar 

  • Oliveira LFG, Souza-Silva F, Côrtes LMC et al (2018) Antileishmanial activity of 2-methoxy-4H-spiro-[naphthalene-1,20-oxiran]-4-one(epoxymethoxy-lawsone): a promising new drug candidate for leishmaniasis treatment. Molecules 23:E864

    Article  PubMed  CAS  Google Scholar 

  • Olliaro PL, Guerin PJ, Gerstl S, Haaskjold AA, Rottingen J-A, Sundar S (2005) Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India,1980–2004. Lancet Infect Dis 5:763–774

    Article  PubMed  Google Scholar 

  • Ortiz D, Guiguemde WA, Hammill JT et al (2017) Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening. PLoS Negl Trop Dis 11:e0006157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oryan A (2015) Plant-derived compounds in treatment of leishmaniasis. Iran J Vet Res 16:1–19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ostyn B, Gidwani K, Khanal B, Picado A, Chappuis F, Singh SP, Rijal S, Sundar S, Boelaert M (2011) Incidence of symptomatic and asymptomatic Leishmania donovani infections in high-endemic foci in India and Nepal: a prospective study. PLoS Negl Trop Dis 5:e1284

    Article  PubMed  PubMed Central  Google Scholar 

  • Pagliero RJ, Kaiser M, Brun R, Nieto MJ, Mazzieri MR (2017) Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles. Bioorg Med Chem Lett 27:3945–3949

    Article  CAS  PubMed  Google Scholar 

  • Panda SK, Luyten W (2018) Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India. Parasite 25:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Pandey A, Sahu D, Bakkali T et al (2012) Estimate of HIV prevalence and number of people living with HIV in India 2008–2009. BMJ Open 2:e000926

    Article  PubMed  PubMed Central  Google Scholar 

  • Pandey RK, Verma P, Sharma D, Bhatt TK, Sundar S, Prajapati VK (2016a) High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania. Biomed Pharmacother 83:141–152

    Article  CAS  PubMed  Google Scholar 

  • Pandey RK, Kumbhar BV, Srivastava S, Malik R, Sundar S, Kunwar A, Prajapati VK (2016b) Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation. J Biomol Struct Dyn 35:141–158

    Article  PubMed  CAS  Google Scholar 

  • Patterson S, Wyllie S, Stojanovski L et al (2013) The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral leishmaniasis. Antimicrob Agents Chemother 57:4699–4706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penta A, Chander S, Smith TK, Sankaranarayanan M (2018) Design, synthesis and biological evaluation of piperazinyl-β-carbolinederivatives as anti-leishmanial agents. Eur J Med Chem 150:559–566

    Article  CAS  Google Scholar 

  • Penta A, Chander S, Smith TK, Singh RP, Jha PN, Sankaranarayanana M (2019) Biological evaluation and structure activity relationship of 9-methyl-1-phenyl-9H-pyrido[3,4-b]indole derivatives as anti-leishmanial agents. Bioorg Chem 84:98–105

    Article  CAS  Google Scholar 

  • Petitti M, Vanni M, Barresi AA (2008) Controlled release of drug encapsulated as a solid core: theoretical model and sensitivity analysis. Chem Eng Res Des 86:1294–1300

    Article  CAS  Google Scholar 

  • Petri e Silva SC, Palace-Berl F, Tavares LC, Soares SR, Lindoso JA (2016) Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes. Exp Parasitol 163:68–75

    Article  CAS  PubMed  Google Scholar 

  • Pigott DM, Golding N, Messina JP et al (2014) Global database of leishmaniasis occurrence locations, 1960-2012. Sci Data 1:140036

    Article  PubMed  PubMed Central  Google Scholar 

  • Ponte-Sucre A, Gamarro F, Dujardin J-C et al (2017) Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis 11:e0006052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prajapati VK, Awasthi K, Yadav TP, Rai M, Srivastava ON, Sundar S (2011) An oral formulation ofamphotericin B attached to functionalized carbon nanotubes is an effective treatment for experimental visceral leishmaniasis. J Infect Dis 205:333–336

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prajapati VK, Mehrotra S, Gautam S, Rai M, Sundar S (2012) In vitro antileishmanial drug susceptibility of clinical isolates from patients with Indian visceral leishmaniasis–status of newly introduced drugs. Am J Trop Med Hyg 87:655–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Purkait B, Kumar A, Nandi N et al (2012) Mechanism of amphotericin B resistancein clinical isolates of Leishmania donovani. Antimicrob Agents Chemother 56:1031–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Purohit P, Pandey AK, Singh D et al (2017) An insight into tetrahydro-β-carboline–tetrazole hybrids: synthesis and bioevaluation as potent antileishmanial agents. Med Chem Commun 8:1824–1834

    Article  CAS  Google Scholar 

  • Rahman M, Ahmed B-N, Faiz MA et al (2011) Phase IV trial of miltefosinein adults and children for treatment of visceral leishmaniasis (kala-azar) in Bangladesh. Am J Trop Med Hyg 85:66–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramesh V, Avishek K, Sharma V, Salotra P (2014) Combination therapy with amphotericin-B and miltefosine for post-kalaaardermal leishmaniasis: a preliminary report. Acta Derm Venereol 94:242–243

    Article  PubMed  Google Scholar 

  • Ramu D, Garg S, Ayana R et al (2017) Novel β-carboline-quinazolinone hybrids disrupt Leishmania donovani redox homeostasis and show promising antileishmanial activity. Biochem Pharmacol 129:26–42

    Article  CAS  PubMed  Google Scholar 

  • Ramu D, Jain R, Kumar RR et al (2019) Design and synthesis of imidazolidinone derivatives as potent anti-leishmanial agents by bioisosterism. Arch Pharm Chem Life Sci 352:e1800290

    Article  CAS  Google Scholar 

  • Ready PD (2013) Biology of phlebotomine sand flies as vectors of disease agents. Annu Rev Entomol 58:227–250

    Article  CAS  PubMed  Google Scholar 

  • Redhu NS, Dey A, Balooni V, Singh S (2006) Leishmania-HIV co-infection: an emerging problem in India. AIDS 20:1213–1215

    Article  PubMed  Google Scholar 

  • Reguera RM, Perez-Pertejo Y, Gutierrez-Corbo C et al (2019) Current and promising novel drug candidates against visceral leishmaniasis. Pure Appl Chem 91:1385–1404

    Article  CAS  Google Scholar 

  • Rijal S, Ostyn B, Uranw S et al (2013) Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis 56:1530–1538

    Article  CAS  PubMed  Google Scholar 

  • Ritmeijer K, Ter Horst R, Chane S, Aderie EM, Piening T, Collin SM, Davidson RN (2011) Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence. Clin Infect Dis 53:e152–e158

    Article  CAS  PubMed  Google Scholar 

  • Romero G, Lessa H, Macedo VO et al (1996) Open therapeutic study with aminosidine sulfate in mucosal leishmaniasis caused by Leishmania (Viannia) braziliensis. Rev Soc Bras Med Trop 29:557–565

    Article  CAS  PubMed  Google Scholar 

  • da Rosa R, de Moraes MH, Zimmermann LA, Schenkel EP, Steindel M, Bernardes LSC (2017) Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis. Eur J Med Chem 128:25–35

    Article  PubMed  CAS  Google Scholar 

  • Roychoudhury J, Sinha R, Ali N (2011) Therapy with sodium stibogluconate in stearylamine-bearing liposomes confers cure against SSG-resistant Leishmania donovani in BALB/c mice. PLoS One 6:e17376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruiz-Santaquiteria M, de Castro S, Toro MA et al (2018) Trypanothione reductase inhibition and anti-leishmanial activity of all-hydrocarbon stapled a-helical peptides with improved proteolytic stability Eur. J Med Chem 149:238–247

    Article  CAS  Google Scholar 

  • Saccoliti F, Angiulli G, Pupo G et al (2017) Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives. J Enzyme Inhib Med Chem 32:304–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saha S, Acharya C, Pal U, Chowdhury SR, Sarkar K, Maiti NC, Jaisankar P, Majumder HK (2016) A novel spirooxindole derivative inhibits the growth of Leishmania donovani parasites both in vitro and in vivo by targeting type IB topoisomerase. Antimicrob Angents Chemother 60:6281–6293

    Article  CAS  Google Scholar 

  • Sangshetti JN, Khan FAK, Kulkarni AA, Arote R, Patil RH (2015) Antileishmanial drug discovery: comprehensive review of the last 10 years. RSC Adv 5:32376–32415

    Article  CAS  Google Scholar 

  • Saudagar P, Dubey VK (2014) Carbon nanotube based betulin formulationshows better efficacy against Leishmania parasite. Parasitol Int 63:772–776

    Article  CAS  PubMed  Google Scholar 

  • Sen Gupta PC (1968) Leishmaniasis in India. J Indian Med Assoc 50:34–36

    Google Scholar 

  • Sesana AM, Monti-Rocha R, Vinhas SA, Morais CG, Dietze R, Lemos EM (2011) In vitro activity of amphotericin B cochleates against Leishmania chagasi. Mem Inst Oswaldo Cruz 106:251–253

    Article  PubMed  Google Scholar 

  • Shio MT, Paquet M, Martel C, Bosschaerts T, Stienstra S, Olivier M, Fortin A (2014) Drug delivery by tattooing to treat cutaneous leishmaniasis. Sci Rep 4:4156

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • da Silva AD, dos Santosa JA, Machadob PA et al (2018) Insights about resveratrol analogs against trypanothione reductase of Leishmania braziliensis: molecular modelling, computational docking and in vitro antileishmanial studies. J Biomol Struct Dyn 37:2960–2969

    Article  PubMed  CAS  Google Scholar 

  • Srivastava P, Prajapati VK, Rai M, Sundar S (2011) Unusual case of resistance to amphotericin B in visceral leishmaniasis in a region in India where leishmaniasis isnot endemic. J Clin Microbiol 49:3088–3091

    Article  PubMed  PubMed Central  Google Scholar 

  • Sundar S (2001) Drug resistance in Indian visceral leishmaniasis. Tropical Med Int Health 6:849–854

    Article  CAS  Google Scholar 

  • Sundar S, Chakravarty J (2013) Leishmaniasis: an update of current pharmacotherapy. Expert Opin Pharmacother 14:53–63

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Chakravarty J (2015) Investigational drugs for visceral leishmaniasis. Expert Opin Investig Drugs 24:43–59

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Chatterjee M (2006) Visceral leishmaniasis-current therapeutic modalities. Indian J Med Res 123:345–352

    CAS  PubMed  Google Scholar 

  • Sundar S, Thakur BB, Tandon AK, Agrawal NR, Mishra CP, Mahapatra TM, Singh VP (1994) Clinico-epidemiological study of drug resistance in Indian kala-azar. Br Med J 308:307

    Article  CAS  Google Scholar 

  • Sundar S, Jha T, Thakur CP, Sinha PK, Bhattacharya SK (2007) Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 356:2571–2581

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Rai M, Chakravarty J, Agarwal D, Agrawal N, Vaillant M, Olliaro P, Murray HW (2008) New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericinB followed by short-course oral miltefosine. Clin Infect Dis 47:1000–1006

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW (2010) Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362:504–512

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Sinha PK, Rai M et al (2011a) Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet 377:477–486

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Sinha PK, Verma DK et al (2011b) Ambisome plus miltefosine for Indian patients with kala-azar. Trans R Soc Trop Med Hyg 105:115–117

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Singh A, Rai M et al (2012) Efficacy of miltefosine in thetreatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 55:543–550

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Singh A, Tiwari A, Shukla S, Chakravarty J, Rai M (2014) Efficacy and safety of paromomycin in treatment of post-kala-azar dermal leishmaniasis. ISRN Parasitol 2014:548010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sundar S, Chakravarty J, Meena LP (2019) Leishmaniasis: treatment, drug resistance and emerging therapies. Expert Opin Orphan Drugs 7:1–10

    Article  CAS  Google Scholar 

  • Tamiru A, Tigabu B, Yifru S, Diro E, Hailu A (2016) Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia. BMC Infect Dis 16:548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Teixeira de Macedo SS, Visbal G, Lima PGJ, Urbina JA, de Souza W, Cola FRJ (2018) In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis. J Antimicrob Chemother 73:2360–2373

    Article  CAS  Google Scholar 

  • Tejería A, Pèrez-Pertejo Y, Reguera RM et al (2019) Antileishmanial activity of new hybrid tetrahydroquinoline and quinoline derivatives with phosphorus substituents. Eur J Med Chem 162:18–31

    Article  PubMed  CAS  Google Scholar 

  • Temraz MG, Elzahhar PA, Bekhit AE-DA, Bekhit AA, Labib HF, Belal ASF (2018) Anti-leishmanial click modifiable thiosemicarbazones: design, synthesis, biological evaluation and in silico studies. Eur J Med Chem 151:585–600

    Article  CAS  PubMed  Google Scholar 

  • Thakur CP, Singh RK, Hassan SM, Kumar R, Narain S, Kumar A (1999) Amphotericin B deoxycholate treatment of visceral leishmaniasis with newer modes of administration and precautions: a study of 938 cases. Trans R Soc Trop Med Hyg 93:319–323

    Article  CAS  PubMed  Google Scholar 

  • Thompson AM, O’Connor PD, Blaser A et al (2016) Repositioning antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for neglected tropical diseases: structure–activity studies on a preclinical candidate for visceral leishmaniasis. J Med Chem 59:2530–2550

    Article  CAS  PubMed  Google Scholar 

  • Thompson AM, O’Connor PD, Marshall AJ et al (2017) 7- Substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines: novel antitubercular agents lead to a new preclinical candidate for visceral leishmaniasis. J Med Chem 60:4212–4233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson AM, O’Connor PD, Marshall AJ et al (2018) Development of (6R)‑2-nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7- dihydro‑5H‑imidazo[2,1‑b][1,3]oxazine (DNDI-8219): a new lead for visceral leishmaniasis. J Med Chem 61:2329–2352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiuman TS, Santosm AO, Ueda-Nakamuram T, Filho BP, Nakamura CV (2011) Recent advances inleishmaniasis treatment. Int J Infect Dis 15:e525–e532

    Article  CAS  PubMed  Google Scholar 

  • Torrado JJ, Serrano DR, Uchegbu IF (2013) The oral delivery of amphotericin B. Ther Deliv 4:9–12

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay A, Kushwaha P, Gupta S, Dodda RP, Ramalingam K, Kant R, Goyal N, Sashidhara KV (2018) Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents. Eur J Med Chem 154:172–181

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay A, Chandrakar P, Gupta S et al (2019) Synthesis, biological evaluation, structure–activity relationship, and mechanism of action studies of quinoline–metronidazole derivatives against experimental visceral leishmaniasis. J Med Chem 62:5655–5671

    Article  CAS  PubMed  Google Scholar 

  • Velásquez AMA, Ribeiro WC, Venn V et al (2017) Efficacy of a binuclear cyclopalladated compound therapy for cutaneous Leishmaniasis in the murine model of infection with Leishmania amazonensis and its inhibitory effect on topoisomerase 1B. Antimicrob Agents Chemother 61:e00688–e00617

    Article  PubMed  PubMed Central  Google Scholar 

  • Vijayakumar S, Das P (2018) Recent progress in drug targets and inhibitors towards combating leishmaniasis. Acta Trop 181:95–104

    Article  CAS  PubMed  Google Scholar 

  • de Vries HJ, Reedijk SH, Schallig HD (2015) Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol 16:99–109

    Article  PubMed  PubMed Central  Google Scholar 

  • Wadhone P, Maiti M, Agarwal R, Kamat V, Martin S, Saha B (2009) Miltefosine promotes IFN-c-dominated anti-leishmanial immune response. J Immunol 182:7146–7154

    Article  CAS  PubMed  Google Scholar 

  • Walkinshaw M (2014) Multiple chemical scaffolds inhibit a promising Leishmania drug target. IUCrJ 1:202–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wasan EK, Gershkovich P, Zhao J et al (2010) A novel tropically stable oral amphotericin B formulation (iCo-010) exhibits efficacy against visceral leishmaniasis in a murine model. PLoS Negl Trop Dis 4:e913

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • WHO (2002) New therapy for visceral leishmaniasis. Wkly Epidemiol Rec 77:205–212

    Google Scholar 

  • WHO (2010) Control of the leishmaniasis: report of a meeting of the World Health Organization Expert Committee on the control of leishmaniasis, Geneva, 2010. World Health Organ Tech Rep Ser 949:1–186

    Google Scholar 

  • WHO (2017) WHO: weekly epidemiological record: global leishmaniasis update, 2006–2015, a turning point in leishmaniasis surveillance. World Health Organ 92:520–525

    Google Scholar 

  • World Health Organization (1995) Report on the consultative meeting on Leishmania/HIV co-infection. Report no. WHO/LEISH/95.35. World Health Organization, Geneva, pp 1–14

    Google Scholar 

  • World Health Organization (2004) Report of the scientific working group meeting on leishmaniasis. World Health Organization, Geneva

    Google Scholar 

  • World Health Organization (2005) Regional strategic framework for elimination of kala-azar from the SouthEast Asia region (2005–2015). World Health Organization, New Delhi

    Google Scholar 

  • World Health Organization (2011) Trend of reported cases of Kala-azar in SEA Region 1994–2011. WHO, Geneva, pp 12–15

    Google Scholar 

  • World Health Organization (2012) Regional strategic framework for elimination of kala-azar from the South East Asia Region (2011–2015). WHO, Geneva

    Google Scholar 

  • World Health Organization, South-East Asia, Government of the People’s Republic of Bangladesh, Royal Government of Bhutan, Government of India, Government of Nepal, Royal Thai Government (2014) Memorandum of understanding among Bangladesh, Bhutan, India, Nepal and Thailand on the elimination of kala-Azar from the South-East Asia Region, Dhaka. WHO, Geneva

    Google Scholar 

  • World Health Organization (2015) World health statistics, 2015. WHO, Geneva. http://www.who.int/gho/publications/world_health_statistics/2015/en/

    Google Scholar 

  • World Health Organization (2019). https://www.who.int.Newsroom.Factsheets.Detail

  • World Health Organization Global Health Observatory (2017) Leishmaniasis. WHO, Geneva. http://www.who.int/gho/neglected_diseases/leishmaniasis/en/

    Google Scholar 

  • Wu G, Zhao T, Kang D et al (2019) Overview of recent strategic advances in medicinal chemistry. J Med Chem 62:9375–9414

    Article  CAS  PubMed  Google Scholar 

  • Wyllie S, Thomas M, Patterson S et al (2018) Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature 560:192–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wyllie S, Brand S, Thomas M et al (2019) Preclinical candidate for the treatment of visceralleishmaniasis that acts through proteasome inhibition. Proc Natl Acad Sci U S A 116:9318–9323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamthe LRT, Appiah-Opong R, Fokou PVT, Tsabang N, Boyom FF, Nyarko AK, Wilson MD (2017) Marine algae as source of novel antileishmanial drugs: a review. Mar Drugs 15:323

    Article  CAS  Google Scholar 

  • Yousuf M, Mukherjee D, Dey S, Pal C, Adhikari S (2016) Antileishmanial ferrocenylquinoline derivatives: synthesis and biological evaluation against Leishmania donovani. Eur J Med Chem 124:468–479

    Article  CAS  PubMed  Google Scholar 

  • Yousuf M, Mukherjee D, Dey S, Chatterjee S, Pal A, Sarkar B, Pal C, Adhikari S (2018) Synthesis and biological evaluation of polyhydroxylated oxindole derivatives as potential antileishmanial agent. Bioorg Med Chem Lett 28:1056–1062

    Article  CAS  PubMed  Google Scholar 

  • Zarif L (2005) Drug delivery by lipid cochleates. Methods Enzymol 391:314–329

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Farahat M, Mattamana AA et al (2016) Synthesis and pharmacological evaluation of mono-arylimidamides as antileishmanial agents. Bioorg Med Chem Lett 26:2551–2556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM (2003) Post-kala-azar dermal Leishmaniasis. Lancet Infect Dis 3:87–98

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochemistry Division, CSIR - Central Drug Research Institute, Lucknow, India

    Neena Goyal

  2. Academy of Scientific and Innovative Research, CSIR - Human Resource Development Centre, Ghaziabad, Uttar Pradesh, India

    Neena Goyal & Sanjay Batra

  3. Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, India

    Manveer Patel & Sanjay Batra

Authors
  1. Neena Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manveer Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanjay Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. NCR Biotech Science Cluster, Translational Health Science and Technology Institute, Faridabad, India

    Madhu Dikshit

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Goyal, N., Patel, M., Batra, S. (2021). Modern Drug Discovery and Development in the Area of Leishmaniasis. In: Dikshit, M. (eds) Drug Discovery and Drug Development. Springer, Singapore. https://doi.org/10.1007/978-981-15-8002-4_5

Download citation

Publish with us

Policies and ethics

Search

Navigation