Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2557–2567 | Cite as

Synthesis, antitubercular and antimicrobial potential of some new thiazole substituted thiosemicarbazide derivatives

  • Yogita K. Abhale
  • Abhijit Shinde
  • Keshav K. Deshmukh
  • Laxman Nawale
  • Dhiman Sarkar
  • Pravin C. Mhaske
Original Research
  • 103 Downloads

Abstract

The increase in antibiotic resistance due to multiple factors has warranted the need for search of new compounds which are active against multidrug resistant pathogens. In this context a small focused library of thiosemicarbazide derivatives of 2-arylthiazole-4-carbaldehyde, 4-methyl-2-arylthiazole-5-carbaldehyde and 1-(4-methyl-2-arylthiazol-5-yl) ethanone, (5al) has been synthesized. The title compounds were screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis Bacille Calmette Guerin (ATCC 35743) strains. The synthesized compounds, 5al were further assayed for their cytotoxic activity against the two human cancer cell lines, HeLa and human colon carcinoma 116 cell lines and showed no significant cytotoxic activity against these two cell lines at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bacteria, Escherichia coli, Pseudomonas flurescence and Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderate activity against fungal strain Candida albicans. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimycobacterial agent.

Keywords

Thiosemicarbazide Thiazole Antitubercular activity Antimicrobial activity Cytotoxicity 

Notes

Acknowledgements

Y.K.A. expresses her gratefulness to CSIR [File No. 08/590(0001)/2012-EMR-I] for the financial support. P.C.M. would like to thank University Grant Commission (UGC No. 42-355/2013(SR), New Delhi, India for the financial assistance and CSIR-NCL, Pune for supporting biological activity. Central Analysis facility, Savitribai Phule Pune University, Pune is also acknowledged for spectral analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1955_MOESM1_ESM.docx (1.4 mb)
Supplementary Information

References

  1. Abhale YK, Deshmukh KK, Sasane AV, Chavan AP, Mhaske PC (2016) Fused heterocycles: synthesis and antitubercular activity of novel 6-substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H imidazo [1,2-a]pyridine. J Heterocyclic Chem 53:229–233CrossRefGoogle Scholar
  2. Abhale YK, Sasane AV, Chavan AP, Deshmukh KK, Kotapalli SS, Ummanni R, Sayyad SF, Mhaske PC (2015) Synthesis and biological screening of 2′-aryl/benzyl-2-aryl-4-methyl-4′,5-bithiazolyls as possible anti-tubercular and antimicrobial agents. Eur J Med Chem 94:340–347CrossRefPubMedGoogle Scholar
  3. Abhale YK, Sasane AV, Chavan AP, Shekh SH, Deshmukh KK, Bhansali S, Nawale L, Sarkar D, Mhaske PC (2017) Synthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives. Eur J Med Chem 132:333–340CrossRefPubMedGoogle Scholar
  4. Achkar JM, Fries BC (2010) Candida infections of the genitourinary tract. Clin Microbiol Rev 23(2):253–273CrossRefPubMedPubMedCentralGoogle Scholar
  5. Alagarsamy V, Arun kumar B, Parthiban P, V Sheorey R, Raja Solomon V (2012) Synthesis and Antibacterial Activity of Some Novel 1-(4-oxo-3-(3- methoxyphenyl)-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides. Anti-Infect Agents 10(2):105–110CrossRefGoogle Scholar
  6. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48(3):589–601PubMedGoogle Scholar
  7. Arora S, Agarwal S, Singhal S (2014) Anticancer activities of thiosemicarbazides / thiosemi-carbazones: a review. Int J Pharm Pharm Sci 6:34–41Google Scholar
  8. Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanabe K, Niimi M, Goffeau A, Monk BC (2009) Efflux-mediated antifungal drug resistance. Clin Microbiol Rev 22(2):291–321CrossRefPubMedPubMedCentralGoogle Scholar
  9. Casas JS, Garcia-Tasende MS, Sordo J (2000) Main Group metal complexes of semicarbazones and thiosemicarbazones. a structural review. Coord Chem Rev 209:197–261CrossRefGoogle Scholar
  10. Chornous VA, Grozav AN, Todoriko LD, Vovk MV (2014) Synthesis and biological activity of 4-chloro-1H-imidazole-5-carbaldehyde thiosemicarbazones. Pharma Chem J 47(10):524–526CrossRefGoogle Scholar
  11. Ciapetti G, Cenni E, Pratelli L, Pizzoferrato A (1993) In vitro evaluation of cell/ biomaterial interaction by MTT assay. Biomaterials 14(5):359–364CrossRefPubMedGoogle Scholar
  12. Gaikwad ND, Patil SV, Bobade VD (2012) Synthesis and biological evaluation of some novel thiazole substituted benzotriazole derivatives. Bioorg Med Chem Lett 22:3449–3454CrossRefPubMedGoogle Scholar
  13. Haraguchi SK, Silva AA, Vidotti GJ, V dos Santos P, Garcia FP, Pedroso RB (2011) Antitrypanosomal activity of novel benzaldehyde-thiosemicarbazone derivatives from kaurenoic acid. Molecules 16(2):1166–1180CrossRefPubMedGoogle Scholar
  14. Inamdar GS, Pandya AN, Thakar HM, Sudarsanam V, Kachler S, Sabbadin D, Moro S, Klotz KN, Vasu KK (2013) New insight into adenosine receptors selectivity derived from a novel series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamides and furamides. Eur J Med Chem 63:924–934CrossRefPubMedGoogle Scholar
  15. Johnson M, Antonio T, Reith ME, Dutta AK (2012) Structure-activity relationship study of N6-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues: development of highly selective D3 dopamine receptor agonists along with a highly potent D2/D3 agonist and their pharmacological characterization. J Med Chem 55(12):5826–5840CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kathiravan MK, Salake AB, Chothe AS, Dudhe PB, Watode RP, Mukta MS, Gadhwe S (2012) The biology and chemistry of antifungal agents: a review. Bioorg Med Chem 20(19):5678–5698CrossRefPubMedGoogle Scholar
  17. Khan A, Sarkar D (2008) A simple whole cell based high throughput screening protocol using Mycobacterium bovis BCG for inhibitors against dormant and active tubercle bacilli. J Microbiol Methods 73:62–68CrossRefPubMedGoogle Scholar
  18. Khan A, Sarkar S, Sarkar D (2008) Bactericidal activity of 2-nitroimidazole against the active replicating stage of Mycobacterium bovis BCG and Mycobacterium tuberculosis with intracellular efficacy in THP-1 macrophages. Int J Antimicrob Agents 32(1):40–45CrossRefPubMedGoogle Scholar
  19. Kucukguzel G, Kocatepe A, De Clercq E, Şahin F, Gulluce M (2006) Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. Eur J Med Chem 41:353–359CrossRefPubMedGoogle Scholar
  20. Kumari S, Sharma NK, KohliS (2012) Synthesis, characterization and antimicrobial studies of copper (II) complexes of semicarbazone and thiosemicarbazone of m-Hydroxy benzaldehydeand p-hydroxy benzaldehyde. Orient J Chem 28:969–974CrossRefGoogle Scholar
  21. Kunin CM, Ellis WY (2000) Antimicrobial activities of mefloquine and a series of related compounds. Antimicrob Agents Chemother 44(4):848–852CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lee YS, Kim H, Kim YH, Roh EJ, Han H, Shin KJ (2012) Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 22(24):7555–7561CrossRefPubMedGoogle Scholar
  23. Leite ACL, de Lima RS, de M Moreira DR, de O Cardoso MV, de Brito Ana CG, dos Santos LMF (2006) Synthesis, docking, and in vitro activity of thiosemicarbazones, aminoacyl-thiosemicarbazides and acyl-thiazolidones against Trypanosoma cruzi. Bioorg Med Chem 14:3749–3757CrossRefPubMedGoogle Scholar
  24. Malik S, Bahare RS, Khan SA (2013) Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: a hybrid pharmacophore approach. Eur J Med Chem 67:1–13CrossRefPubMedGoogle Scholar
  25. Malki A, Elbayaa RY, Ashour HM, Loffredo CA, Youssef AM (2015) Novel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling. J Enzyme Inhib Med Chem 30(5):786–795CrossRefPubMedGoogle Scholar
  26. Moglea PP, Meshramb RJ, Hesea SV, Kamblea RD, Kambleb SS, Gaccheb RN, Dawanea BS (2016) Synthesis and molecular docking studies of new series of bipyrazol-ylthiazol-ylidene-hydrazinecarbothioamide derivatives as potential antitubercular agents. MedChemCom 7:1405-1420Google Scholar
  27. Mavrova AT, Wesselinova D, Tsenov JA, Lubenov LA (2014) Synthesis and antiproliferative activity of some new thieno[2,3-d]pyrimidin-4(3H)-ones containing 1,2,4-triazole and 1,3,4-thiadiazole moiety. Eur J Med Chem 86:676–683CrossRefPubMedGoogle Scholar
  28. Mishra CB, Kumari S, Tiwari M (2015) Thiazole: a promising heterocycle for the development of potent CNS active agents. Eur J Med Chem 92:1–34CrossRefPubMedGoogle Scholar
  29. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1-2):55–63CrossRefPubMedGoogle Scholar
  30. Navale A, Pawar S, Deodhar M, Kale A (2013) Synthesis of substituted benzo[d]thiazol-2-ylcarbamates as potential anticonvulsants. Med Chem Res 22(9):4316–4321CrossRefGoogle Scholar
  31. Patel SR, Gangwal R, Sangamwar AT, Jain R (2014) Synthesis, biological evaluation and 3D-QSAR study of hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1- yl)quinoline as anti-tuberculosis agents. Eur J Med Chem 85:255–267CrossRefPubMedGoogle Scholar
  32. Perkoviisć I, Butula I, Kralj M, Martin-Kleiner I, Balzarini J, Hadjipavlou-Litina D, Katsori AM, Zorc B (2012) Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/hydroxyl carbamoylcarbazides as potential anticancer agents and antioxidants. Eur J Med Chem 51:227–238CrossRefGoogle Scholar
  33. Pitucha M, Wos´ M, Miazga-Karska M, Klimek K, Mirosław B, Pachuta-Stec A, Gładysz A, Ginalska G (2016) Synthesis, antibacterial and antiproliferative potential of somenew 1-pyridinecarbonyl-4-substituted thiosemicarbazidederivatives. Med Chem Res 25:1666–1677CrossRefPubMedPubMedCentralGoogle Scholar
  34. Plech T, Wujec M, Siwek A, Kosikowska U, Malm A (2011) Synthesis and antimicrobial activity of thiosemicarbazides, s-triazoles and their Mannich bases bearing 3-chlorophenyl moiety. Eur J Med Chem 46(1):241–248CrossRefPubMedGoogle Scholar
  35. Rane RA, Naphade SS, Bangalore PK, Palkar MB, Shaikh MS, Karpoormath R (2014) Synthesis of novel 4-nitropyrrole-basedsemicarbazide and thiosemicarbazide hybrids with antimicrobial and anti-tubercular activity. Bioorg Med Chem Lett 24:3079–3083CrossRefPubMedGoogle Scholar
  36. Sarkar S, Sarkar D (2012) Potential Use of Nitrate Reductase as a Biomarker for the Identification of Active and Dormant Inhibitors of Mycobacterium tuberculosis in a THP1 Infection Model. J Biomol Screen 17(7):966–973CrossRefPubMedGoogle Scholar
  37. Salgın-Goksen U, Gokhan-Kelekci N, Goktas O, Koysal Y, Kılıc E, Isık S, Aktay G, Ozalp M (2007) 1-Acylthiosemicarbazides,1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: synthesis, analgesic, anti-inflammatory and antimicrobial activities. Bioorg Med Chem 15:5738–5751CrossRefPubMedGoogle Scholar
  38. Sheikhy M, Jalilian AR, Novinrooz A, Motamedi-Sedeh F (2012) Synthesis and in vitro antibacterial evaluation of some thiosemicarbazides and thiosemicarbazones. J Biomed Sci Eng 5:39–42CrossRefGoogle Scholar
  39. Siddiqui N, Ahsan W (2010) Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening. Eur J Med Chem 45(4):1536–1543CrossRefPubMedGoogle Scholar
  40. Singh R, Nawale LU, Arkile M, Shedbalkar UU, Wadhwani SA, Sarkar D, Chopade BA (2015) Chemical and biological metal nanoparticles as antimycobacterial agents: a comparative study. Int J Antimicrob Agents 46(2):183–188CrossRefPubMedGoogle Scholar
  41. Singh U, Akhtar S, Mishra A, Sarkar D (2011) A novel screening method based on menadione mediated rapid reduction of tetrazolium salt for testing of anti-mycobacterial agents. J Microbiol Methods 84:202–207CrossRefPubMedGoogle Scholar
  42. Sriram D, Yogeeswari P, Thirumurugan R, Pavana RK (2006) Discovery of new antitubercular oxazolyl thiosemicarbazones. J Med Chem 49:3448–3450CrossRefPubMedGoogle Scholar
  43. Tan OU, Ozadali K, Yogeeswari P, Sriram D, Balkan A (2012) Synthesis and antimycobacterial activities of some new N-acylhydrazoneand thiosemicarbazide derivatives of 6-methyl-4,5-dihydropyridazin-3(2H)-one. Med Chem Res 21:2388–2394CrossRefGoogle Scholar
  44. Tomasic T, Katsamakas S, Hodnik Z, Ilas J, Brvar M, Solmajer T, Montalvao S, Tammela P, Banjanac M, Ergovic G, Anderluh M, Masic LP, Kikelj D (2015) Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site. J Med Chem 58:5501–5521CrossRefPubMedGoogle Scholar
  45. Umadevi P, Deepti K, Srinath I, Vijayalakshmi G, Tarakaramji M (2012) Synthesis and in vitro antibacterial activity of some urea, thiourea and thiosemicarbazide derivatives. Int J Pharm Pharm Sci 4(3):379–383Google Scholar
  46. Urbanek RA, Xiong H, Wu Y, Blackwell W, Steelman G, Rosamond J, Wesolowski SS, Campbell JB, Zhang M, Brockel B, Widzowski DV (2013) Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists. Bioorg Med Chem Lett 23(2):543–547CrossRefPubMedGoogle Scholar
  47. Yusufzai SK, Osman H, Khan MS, Mohamad S, Sulaiman O, Parumasivam T, Gansau JA, Johansah N, Noviany (2017) Design, characterization, in vitro antibacterial, antitubercular evaluation and structure–activity relationships of new hydrazinyl thiazolyl coumarin derivatives. Med Chem Res. doi: 10.1007/s00044-017-1820-2
  48. Zhang HJ, Qian Y, Zhu DD, Yang XG, Zhu HL (2011) Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents. Eur J Med Chem 46:4702–4708CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yogita K. Abhale
    • 1
  • Abhijit Shinde
    • 2
  • Keshav K. Deshmukh
    • 1
  • Laxman Nawale
    • 3
  • Dhiman Sarkar
    • 3
  • Pravin C. Mhaske
    • 2
  1. 1.Post-Graduate Department of Chemistry and Research Centre, S. N. Arts, D. J. M. Commerce and B. N. S. Science CollegeSavitribai Phule Pune UniversitySangamnerIndia
  2. 2.Post Graduate Department of Chemistry, S. P. Mandali’s Sir Parashurambhau CollegeSavitribai Phule Pune UniversityPuneIndia
  3. 3.CombiChemBio Resource CentreCSIR-National Chemical LaboratoryPuneIndia

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