Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and in vitro evaluation of substituted tetrahydroquinoline-isoxazole hybrids as anticancer agents

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of isoxazole linked to 4-(2-oxopyrrolinidyl-1)-tetrahydroquinoline derivatives was efficiently synthesized. The synthetic route started with the formation of the corresponding N-propargyl tetrahydroquinoline derivatives via cationic Povarov reaction. Tetrahydroquinoline-isoxazole hybrid systems (3a–p) were obtained with good yields (42–88%) through a 1,3-dipolar cycloaddition reaction with a click chemistry approach. These compounds have been tested for their in vitro cytotoxic activity against four different human cancer cell lines, lung (A549), liver (HepG2), and melanoma murine (B16F10) using the conventional MTT assay. Among all tetrahydroquinoline-isoxazole hybrids synthesized, compounds 3a, 3e, 3j, and 3m showed promising in vitro activity against HepG2 cancer cell line with considerable selectivity. Compounds 3a (IC50 = 6.80 µM, SI = 14.7) and 3j (IC50 = 5.20 µM, SI > 16.1) exhibited the highest cytotoxic effect. The death pathway related to cytotoxicity of the compound 3j showed necrotic characteristics selectively on the tumor cell line, also showed an improved in vitro activity against the tested reference drug (oxaliplatin), without significant affectation on the viability of hepatocytes. In general, results suggested that these type of hybrid compounds might have therapeutic potential in future investigations on hepatocellular carcinoma.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abdel Rahman AM, Ryczko M, Pawling J, Dennis JW (2013) Probing the hexosamine biosynthetic pathway in human tumor cells by multitargeted Tandem Mass Spectrometry. ACS Chem Biol 8:2053–2062

    Article  CAS  PubMed  Google Scholar 

  • Acelas M, Kouznetsov VV, Romero Bohórquez AR (2018) Facile and highly diastereo and regioselective synthesis of novel octahydroacridine-isoxazole and octahydroacridine-1,2,3-triazole molecular hybrids from citronella essential oil. Mol Divers 23:189–193

    Google Scholar 

  • Agarwal D, Gupta RD, Awasthi SK (2017) Are antimalarial hybrid molecules a close reality or a distant dream? Antimicrob Agents Chemother 61:1–12

    Article  Google Scholar 

  • Alfarouk KO, Stock C-M, Taylor S, Walsh M, Muddathir AK, Verduzco D, Bashir AHH, Mohammed OY, Elhassan GO, Harguindey S, Reshkin SJ, Ibrahim ME, Rauch C (2015) Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int 15:71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson A, Bowman A, Boulton SJ, Manning P, Birch-Machin MA (2014) A role for human mitochondrial complex II in the production of reactive oxygen species in human skin. Redox Biol 2:1016–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Ghorab MM, Noaman E (2010) Discovering some novel tetrahydroquinoline derivatives bearing the biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem 45:1849–1853

    Article  CAS  PubMed  Google Scholar 

  • Al-Sanea MM, El-Deeb IM, Lee SH (2013) Design, synthesis and in-vitro screening of new 1h-pyrazole and 1,2-isoxazole derivatives as potential inhibitors for ROS and mapk14 kinases. Bull Korean Chem Soc 34:437–442

    Article  CAS  Google Scholar 

  • Álvarez Santos MR, Duarte YB, Güiza FM, Romero Bohórquez AR, Mendez-Sanchez SC (2019) Effects of new tetrahydroquinoline-isoxazole hybrids on bioenergetics of hepatocarcinoma Hep-G2 cells and rat liver mitochondria. Chem Biol Interact. https://doi.org/10.1016/j.cbi.2019.02.002

  • Asolkar RN, Schroeder D, Heckmann R, Lang S, WagnerDoebler I, Laatsch H (2004) Marine bacteria XXVII. Helquinoline, a new tetrahydroquinoline antibiotic from Janibacter limosus Hel 1. J Antibiot 57:17–23

    Article  CAS  PubMed  Google Scholar 

  • Berghe TV, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15:135–147

    Article  CAS  Google Scholar 

  • Bueno Y, Ramírez JV, Güiza FM, Méndez SC, Romero-Bohórquez AR (2018) Synthesis and in vitro evaluation of cytotoxic effect on cervical cancer cells (HELA) of tetrahydroquinoline-isoxazole hybrid derivatives. Res J Pharm Biol Chem Sci 9:420–432

    CAS  Google Scholar 

  • Champa D, Orlacchio A, Patel B, Ranieri M, Shemetov AA, Verkhusha VV, Cuervo AM, Di Cristofano A (2016) Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis. Oncotarget 7:34453–34471

    Article  PubMed  PubMed Central  Google Scholar 

  • Chauhan R, Siddiqi AA, Dwivedi J (2012) An approach to regioselective synthesis of pyrazole and isoxazole derivatives and study of their antimicrobial effect. Pharm Chem J 46:316–320

    Article  CAS  Google Scholar 

  • Chen W, Lin Z, Ning M, Yang C, Yan X, Xie Y et al. (2007) Aza analogues of equol: novel ligands for estrogen receptor beta. Bioorg Med Chem 15:5828–5836

    Article  CAS  PubMed  Google Scholar 

  • Cirrincione G, Barraja P, Diana P, Carbone A, Kelter G, Fiebig H-H (2010) Synthesis and antitumor activity of 2,5-bis(3’-indolyl)-furans and 3,5-bis(3’-indoliy)-isoxazoles, nortopsentin analogues. Bioorg Med Chem 18:4524–4529

    Article  CAS  PubMed  Google Scholar 

  • Cooper G, Husman R (2007) La célula. Marbán Libros, Madrid

    Google Scholar 

  • Cury-Boaventura MF, Pompéia C, Curi R (2004) Comparative toxicity of oleic acid and linoleic acid on Jurkat cells. Clin Nutr 23:721–732

    Article  CAS  PubMed  Google Scholar 

  • Darwish ES, Atia KA, Farag AM (2014) Synthesis and antimicrobial evaluation of some isoxazole based heterocycles. Heterocycles 89:1393–1411

    Article  CAS  Google Scholar 

  • Divakaruni AS, Paradyse A, Ferrick DA, Murphy AN, Jastroch M (2014) Analysis and interpretation of microplate-based oxygen consumption and pH data. Methods Enzymol 547:275–307

    Article  Google Scholar 

  • Duan Y-T, Man R-J, Tang D-J, Yao Y-F, Tao X-X, Yu C, Liang X-Y, Makawana JA, Zou MJ, Wang Z-C, Zhu H-L (2016) Design, synthesis and antitumor activity of novel link-bridge and B-ring modified combretastatin A-4 (CA-4) analogues as potent antitubulin agents. Sci Rep 6:25387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eddington ND, Cox DS, Roberts RR, Butcher RJ, Edafiogho IO, Stables JP, Cooke N, Goodwin AM, Smith CA, Scott KR (2002) Synthesis and anticonvulsant activity of enaminones: 4. Investigations on isoxazole derivatives. Eur J Med Chem 37:635–648

    Article  CAS  PubMed  Google Scholar 

  • Faidallah HM, Rostom S (2013) Synthesis, in vitro antitumor evaluation and DNA-binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems. Eur J Med Chem 63:133–143

    Article  CAS  PubMed  Google Scholar 

  • Fang X-F, Li D, Reddy VK, Gopala L, Gao W-W, Zhou C-H (2017) Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: design, synthesis and bioactive evaluation. Bioorg Med Chem Lett 27:4964–4969

    Article  CAS  PubMed  Google Scholar 

  • Fato R, Bergamini C, Bortolus M, Maniero AL, Leoni S, Ohnishi T, Lenaz G (2009) Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species. Biochim Biophys Acta 1787:384–392

    Article  CAS  PubMed  Google Scholar 

  • Fonseca-Berzal C, Merchán DR, Romero Bohórquez AR, Escario JA, Kouznetsov VV, Gómez-Barrio A (2013) Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase. Bioorg Med Chem Lett 23:4851–4856

    Article  CAS  PubMed  Google Scholar 

  • Gao W, Xu K, Li P, Tang B (2011) Funtional roles of superoxide and hydrogen peroxide generated by mitochondrial DNA mutation in regulating tumorigenicity of HepG2 cells. Cell Biochem Funct 29:400–407

    Article  CAS  PubMed  Google Scholar 

  • Germano D, Tinessa V, Barletta E, Cannella L, Daniele B (2013) Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib. Drugs Aging 30:887–892

    Article  CAS  PubMed  Google Scholar 

  • Goli N, Mainkar PS, Kotapalli SS, Tejaswini K, Ummanni R, Chandrasekhar S (2017) Expanding the tetrahydroquinoline pharmacophore. Bioorg Med Chem Lett 27:1714–1720

    Article  CAS  PubMed  Google Scholar 

  • Gorrini C, Harris IS, Mak T (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12:931–947

    Article  CAS  PubMed  Google Scholar 

  • Hensley CT, Wasti AT, DeBerardinis RJ (2016) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest 123:3678–3684

    Article  CAS  Google Scholar 

  • Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG (2016) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714–726

    Article  CAS  Google Scholar 

  • Hou X, Luo H, Zhong H, Wu F, Zhou M, Zhang W, Han X, Yan G, Zhang M, Lu L, Ding Z, He G, Li R (2013) Analysis of furo[3,2-c]tetrahydroquinoline and pyrano[3,2-c]tetrahydroquinoline derivatives as antitumor agents and their metabolites by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 27:1222–1230

    Article  CAS  PubMed  Google Scholar 

  • Ishiguro H, Toi M (2012) How to dose cytotoxic chemotherapeutic drugs. Curr Top Pharmacool 16:67–81

    CAS  Google Scholar 

  • Kamal A, Bharathi EV, Reddy JS, Ramaiah MJ, Dastagiri D, Reddy MK, Viswanath A, Reddy TL, Shaik TB, Pushpavalli SN, Bhadra MP (2011) Synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole linked 2,3-dihydroquinazolinone hybrids as anticancer agents. Eur J Med Chem 46:691–703

    Article  CAS  PubMed  Google Scholar 

  • Kerru N, Singh P, Koorbanally N, Raj R, Kumar V (2017) Recent advances (2015–2016) in anticancer hybrids. Eur J Med Chem 142:179–212

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Bawa S, Gupta H (2009) Biological activities of quinoline derivatives. Min Rev Med Chem 9:1648–1654

    Article  CAS  Google Scholar 

  • Kumar A, Srivastava S, Gupta G, Chaturvedi V, Sinha S, Srivastava R (2011) Natural product inspired diversity oriented synthesis of tetrahydroquinoline scaffolds as antitubercular agent. ACS Comb Sci 13:65–71

    Article  CAS  PubMed  Google Scholar 

  • Kumar B, Sharma P, Gupta VP, Khullar M, Singh S, Dogra N, Kumar V (2018) Synthesis and biological evaluation of pyrimidine bridged combretastatin derivatives as potential anticancer agents and mechanistic studies. Bioorg Chem 78:130–140

    Article  CAS  PubMed  Google Scholar 

  • Kumbhare RM, Kosurkar UB, Janaki Ramaiah M, Dadmal TL, Pushpavalli SN, Pal-Bhadra M (2012) Synthesis and biological evaluation of novel triazoles and isoxazoles linked 2-phenyl benzothiazole as potential anticancer agents. Bioorg Med Chem Lett 22:5424–5427

    Article  CAS  PubMed  Google Scholar 

  • Lam KH, Lee KK, Gambari R, Wong RS, Cheng GY, Tong SW, Chan KW, Lau FY, Lai PB, Wong WY, Chan AS, Kok SH, Tang JC, Chui CH (2013) Preparation of galipea officinalis hancock type tetrahydroquinoline alkaloid analogues as anti-tumour agents. Phytomedicine 20:166–171

    Article  CAS  PubMed  Google Scholar 

  • LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231

    Article  CAS  PubMed  Google Scholar 

  • Lin CY, Chang TW, Hsieh WH, Hung MC, Lin IH, Lai SC, Tzeng YJ (2016) Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells. Cell Death Discov 2:16065.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17

    Article  Google Scholar 

  • Liu AL, Shu SH, Qin HL, Lee SM, Wang YT, Du GH (2009) In vitro anti-influenza viral activities of constituents from Caesalpinia sappan. Planta Med 75:337–339

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Yu LF, Eaton JB, Caldarone B, Cavino K, Ruiz C, Terry M, Fedolak A, Wang D, Ghavami A, Lowe DA, Brunner D, Lukas RJ, Kozikowski AP (2011) Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression. J Med Chem 54:7280–7288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manzione L, Grimaldi AM, Romano R, Ferrara D, Dinota A (2008) Hepatocarcinoma: from pathogenic mechanisms to target therapy. Oncol Rev 2:214–222

    Article  Google Scholar 

  • Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H (2015) Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol 35:S78–S103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall KD, Baines CP (2014) Necroptosis: is there a role for mitochondria? Front Physiol. 5:323.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  • Muregi FW, Ishih A (2010) Next-generation antimalarial drugs: hybrid molecules as a new strategy in drug design. Drug Dev Res 71:20–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nwaukwa SO, Keehn PM (1989) Ring chlorination of benzenoid compounds using calcium hypochlorite [Ca(OCl)2]. Synth Commun 19:799–804

    Article  CAS  Google Scholar 

  • Palanisamy P, Jenniefer SJ, Muthiah PT, Kumaresan S (2013) Synthesis, characterization, antimicrobial, anticancer, and antituberculosis activity of some new pyrazole, isoxazole, pyrimidine and benzodiazepine derivatives containing thiochromeno and benzothiepino moieties. RSC Adv 3:19300–19310

    Article  CAS  Google Scholar 

  • Palusa SKG, Udupi RH, Himabindu V (2011) Synthesis, antimicrobial and anti-inflammatory studies of isoxazole analogues of rosuvastatin. Der Pharma Chem 3:39–50

    CAS  Google Scholar 

  • Pesi B, Giudici F, Moraldi L, Montesi G, Romagnoli S, Pinelli F, Batignani G (2016) Hepatocellular carcinoma on cirrhosis complicated with tumoral thrombi extended to the right atrium: results in three cases treated with major hepatectomy and thrombectomy under hypothermic cardiocirculatory arrest and literature review. World J Surg Oncol 14:83.

    Article  PubMed  PubMed Central  Google Scholar 

  • Philipp S, Sosna J, Adam D (2016) Cancer and necroptosis: friend or foe? Cell Mol Life Sci 73:2183–2193

    Article  CAS  PubMed  Google Scholar 

  • Raymond E, Faivre SJ, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25 2(suppl 5):4–12

    Google Scholar 

  • Reczek CR, Chandel NS (2017) The two faces of reactive oxygen species in cancer. Annu Rev Cancer Biol 1:4.1–4.20

    Article  Google Scholar 

  • Reyes-Habito CM, Roh EK (2014) Cutaneous reactions to chemotherapeutic drugs and targeted therapy for cancer: part II. Targeted therapy. J Am Acad Dermatol 71:217.e1–217.e11

    Article  CAS  Google Scholar 

  • Rodríguez YA, Gutiérrez M, Ramírez D, Alzate-Morales J, Bernal CC, Güiza FM, Romero Bohórquez AR (2016) Novel N‐allyl/propargyl tetrahydroquinolines: synthesis via three-component cationic imino Diels–Alder reaction, binding prediction, and evaluation as cholinesterase inhibitors. Chem Biol Drug Des 88:498–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romero Bohórquez AR, Escobar P, Leal SM, Kouznetsov VV (2012) In vitro activity against Trypanosoma cruzi and Leishmania chagasi parasites of 2,4-diaryl 1,2,3,4-tetrahydroquinoline derivatives. Lett Drug Des Discov 9:802–808

    Article  Google Scholar 

  • Rudenko DA, Shavrina TV, Shurov SN, Zykova SS (2014) Synthesis and antioxidant activity of tricyclic compounds containing a 5,6,7,8-tetrahydroquinoline moiety. Pharm Chem J 48:100–103

    Article  CAS  Google Scholar 

  • Sangshetti JN, Khan K, Firoz AK, Abhishek AA, Rohidas P, Rajendra H (2015) Antileishmanial drug discovery: comprehensive review of the last 10 years. RSC Adv 5:32376–32415

    Article  CAS  Google Scholar 

  • Sharma S, Gupta MK, Saxena AK, Singh Bedi PM (2017) Thiazolidinone constraint combretastatin analogs as novel antitubulin agents: design, synthesis, biological evaluation and docking studies. Anticancer Agents Med Chem 17:230–240

    Article  CAS  PubMed  Google Scholar 

  • Shen YC, Ou DL, Hsu C, Lin KL, Chang CY, Lin CY, Liu SH, Cheng AL (2013) Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer 108:72–81

    Article  CAS  PubMed  Google Scholar 

  • Singer JM, Barr BM, Coughenour LL, Walters MA (2005) 8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity. Bioorg Med Chem Lett 15:4560–4563

    Article  CAS  PubMed  Google Scholar 

  • Sridharan V, Suryavanshi PA, Menéndez JC (2011) Advances in the chemistry of tetrahydroquinolines. Chem Rev 111:7157–7259

    Article  CAS  PubMed  Google Scholar 

  • Su Z, Yang Z, Xie L, Dewitt JP, Chen Y (2016) Cancer therapy in the necroptosis era. Cell Death Differ 23:748–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sysak A, Obmińska-Mrukowicz B (2017) Isoxazole ring as a useful scaffold in a search for new therapeutic agents. Eur J Med Chem 137:292–309

    Article  CAS  PubMed  Google Scholar 

  • Tartarone A, Lazzari C, Lerose R, Conteduca V, Improta G, Zupa A, Bulotta A, Aieta M, Gregorc V (2013) Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib. Lung Cancer 81:328–36

    Article  PubMed  Google Scholar 

  • Veeraswamy B, Kurumurthy C, Kumar GS, Rao PS, Thelakkat K, Kotamraju S, Narsaiah B (2012) Synthesis of novel 5-substituted isoxazole-3-carboxamide derivatives and cytotoxicity studies on lung cancer cell line. Indian J Chem Sect B 51:1369–1375

    Google Scholar 

  • Vermes I, Haanen C, Steffens-Nakken H, Reutellingsperger C (1995) A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 184:39–51

    Article  CAS  PubMed  Google Scholar 

  • Wu W, Liu P, Li J (2012) Necroptosis: an emerging form of programmed cell death. Crit Rev Oncol Hematol 82:249–258

    Article  PubMed  Google Scholar 

  • Zhang HZ, Zhao ZL, Zhou CH (2018) Recent advance in oxazole-based medicinal chemistry. Eur J Med Chem 144:444–492

    Article  CAS  PubMed  Google Scholar 

  • Zhao J-J, Yan T, Zhao H, Zhou J-G, Huang Z, Zhang Y-F, Cai J-Q (2015) Evaluation of eight different clinical staging systems associated with overall survival of Chinese patients with hepatocellular carcinoma. Chin Med J 128:316–321

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou C, Chen Z, Lu X, Wu H, Yang Q, Xu D (2016) Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells. Tumor Biology 37:3135–3144

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Cheng Y, Li A (2013) Mechanisms of drug resistance to sorafenib in hepatocellular carcinoma. Chin Pharmacol Bull 6:752–755

    Google Scholar 

Download references

Acknowledgements

This research was supported by “Patrimonio Autónomo, Fondo Nacional de Financiamiento para la Ciencia Francisco José de Caldas” (Colciencias) contract code 110265842934. FMG thanks COLCIENCIAS for his fellowship.

Author information

Author notes

  1. These authors contributed equally: Yenny Bueno Duarte, Fausto M. Güiza

Authors and Affiliations

  1. Grupo de Investigación en Compuestos Orgánicos de Interés Medicinal (CODEIM), Parque Tecnológico Guatiguará, Universidad Industrial de Santander, Piedecuesta, Bucaramanga, A.A. 678, Colombia

    Fausto M. Güiza, Yenny Bueno Duarte, Stelia C. Mendez-Sanchez & Arnold R. Romero Bohórquez

  2. Grupo de investigación en Bioquímica y Microbiología (GIBIM), Parque Tecnológico Guatiguará, Universidad Industrial de Santander, Piedecuesta, Bucaramanga, A.A. 678, Colombia

    Yenny Bueno Duarte & Stelia C. Mendez-Sanchez

Authors
  1. Fausto M. Güiza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yenny Bueno Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stelia C. Mendez-Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arnold R. Romero Bohórquez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arnold R. Romero Bohórquez.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher′s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Güiza, F.M., Duarte, Y.B., Mendez-Sanchez, S.C. et al. Synthesis and in vitro evaluation of substituted tetrahydroquinoline-isoxazole hybrids as anticancer agents. Med Chem Res 28, 1182–1196 (2019). https://doi.org/10.1007/s00044-019-02363-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-019-02363-z

Keywords

Search

Navigation