Drug Res (Stuttg) 2018; 68(02): 72-79
DOI: 10.1055/s-0043-116947
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Multicomponent Synthesis of Some Molecular Hybrid Containing Thiazole Pyrazole as Apoptosis Inducer

Parvin Kumar
1   Department of Chemistry, Kurukshetra University Kurukshetra-136119
,
Meenakshi Duhan
1   Department of Chemistry, Kurukshetra University Kurukshetra-136119
,
Kulbir Kadyan
1   Department of Chemistry, Kurukshetra University Kurukshetra-136119
,
Jitender Kumar Bhardwaj
2   Reproductive Physiology Laboratory, Department of Zoology,Kurukshetra University Kurukshetra-136119
,
Priyanka Saraf
2   Reproductive Physiology Laboratory, Department of Zoology,Kurukshetra University Kurukshetra-136119
,
Meenu Mittal
2   Reproductive Physiology Laboratory, Department of Zoology,Kurukshetra University Kurukshetra-136119
› Author Affiliations
Further Information

Publication History

received 07 June 2017

accepted 14 July 2017

Publication Date:
14 September 2017 (online)

Abstract

The present study describes a multicomponent synthesis of molecular hybrid containing pyrazole, thiazole moiety using hydrazone as a linker, which have been synthesized by condensation of 1-phenyl-3-(aryl)-1H-pyrazole-4-carbaldehydes 1a-b, thiosemicarbazide and α-bromoketones 2a-c.The target hybrid compounds, 1-((1-phenyl-3-aryl-1H-pyrazole-4-yl)methylene)-2-(4-arylthiazole-2-yl)hydrazine 3a-f are characterized by 1H-NMR, 13C NMR, FT-IR and mass. Apoptosis inducing ability and cytotoxic nature of all the hybrid compounds having thiazole, pyrazole and hydrazone were assessed by using biological assays viz morphological, fluorescence and tunel assays on granulosa cells of ovarian antral follicles of goat (Capra hircus) in vitro. Apoptosis was recognized and quantified using differential staining of ethidium bromide and acridine orange where apoptotic cells exhibited red fluorescence and live normal cells with intact cell membrane and normal nucleus displayed bright green fluorescence. Among the tested compounds, compound 3e and 3b showed the maximum potency to induce apoptosis with percentage of apoptosis 25.61±2.95and 23.45±1.46 respectively followed by 3f (20.95±0.40) and 3d (20.44±1.60) in comparison with control (5.14±0.44).

Supplementary Material

 
  • References

  • 1 Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol 2007; 35: 495-516
  • 2 Namvaran A, Fazeli M, Farajnia S. et al. Apoptosis and caspase 3 pathway role on anti-proliferative effects of scrophulariaoxy sepala methanolic extract on caco-2 cells. Drug Res DOI: 10.1055/s-0043-110483.
  • 3 Sindhu J, Singh H, Khurana JM. et al. Synthesis and biological evaluation of some functionalized1H-1,2,3-triazole tethered pyrazolo[3,4-b]pyridin-6(7H)-ones asantimicrobial and apoptosis inducing agents. Med Chem Res 2016; 25: 1813-1830
  • 4 Hanhan D, Weinberg RA. (2000) The hallmarks of cancer. Cell 2000; 100: 57-70
  • 5 Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456-1462
  • 6 Zhu XX, Yu QS, Cutler RG. et al. Novel p53 Inactivators with neuroprotective action:  Syntheses and pharmacological evaluation of 2-Imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-Imino-2,3,4,5,6,7-hexahydrobenzoxazole Derivatives. J Med Chem 2000; 45: 5090-5097
  • 7 Yuan J, Yanker BA. Apoptosis in the nervous system. Nature 2000; 407: 802-809
  • 8 Hu W, Kavanagh JJ. Anticancer therapy targeting the apoptoticpathway. Lancet Oncol 2003; 4: 721-729
  • 9 Pawar CD, Sarkate AP, Karnik KS. et al. Synthesis and antimicrobial evaluation of novel ethyl 2-(2-(4-substituted)acetamido)-4-subtituted-thiazole-5-carboxylate derivatives. Bioorg Med Chem Lett 2016; 26: 3525-3528
  • 10 Łaczkowski KZ, Switalska M, Łaczkowska AB. et al. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines. J Mol Struct 2016; 1119: 139-150
  • 11 Koufaki M, Kiziridi C, Nikoludaki F. et al. Designand synthesis of 1,2-dithiolane derivatives and evaluation oftheir neuroprotective activity. Bioorg Med Chem Lett 2007; 17: 4223-4227
  • 12 Kamblea RD, Meshramb RJ, Hesea SV. et al. Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents. Comput Biol Chem 2016; 61: 86-96
  • 13 Shih MH, Ying KF. Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives. Bioorg Med Chem 2004; 12: 4633-4643
  • 14 Gulsory E, Guzeldemirci NU. Synthesis and primary cytotoxicityevaluation of new imidazo [2,1-b] thiazole derivatives. Eur J Med Chem 2007; 42: 320-326
  • 15 Silva EB, Silva DAO, Oliveira AR. et al. Design and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death. Eur J Med Chem DOI: 10.1016/j.ejmech.2017.02.026.
  • 16 Rao AVS, Swapna K, Shaik SP. et al. Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers. Bioorg Med Chem 2017; 25: 977-999
  • 17 Zitouni GT, Altıntop MD, Ozdemir A. et al. Synthesis and evaluation of bis-thiazole derivatives as new anticancer agents. Eur J Med Chem 2016; 107: 288-294
  • 18 Hafez HN, El-Gazzar ARBA, Al-Hussain SA. Novel pyrazole derivatives with oxa/thiadiazolyl, pyrazolyl moieties and pyrazolo[4,3-d]-pyrimidine derivatives as potential antimicrobial and anticancer agents. Bioorg Med Chem Lett 2016; 26: 2428-2433
  • 19 Nagamallu R, Srinivasan B, Ningappa MB. et al. Synthesis of novel coumarin appended bis(formylpyrazole) derivatives: Studies on their antimicrobial and antioxidant activities. Bioorg Med Chem Lett 2016; 26: 690-694
  • 20 Kumar RS, Arif IA, Ahamed A. et al. Anti-inflammatory and antimicrobial activities of novel pyrazole analogues. Saudi. J Biol Sci 2016; 23: 614-620
  • 21 Dev J, Poornachandra Y, Reddy KR. et al. Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modelling and CoMF Aanalysis. Eur J Med Chem DOI: 10.1016/j.ejmech.2017.02.052.
  • 22 Toton E, Ignatowicz E, Bernard MK. et al. Evaluation of Apoptotic Activity of new condensed pyrazole derivative. J Physiol Pharmacol 2013; 64: 115-123
  • 23 Ding XL, Zhang HY, Qi L. et al. Synthesis of novel pyrazole carboxamide derivatives and discovery of modulators for apoptosis or autophagy in A549 lung cancer cells. Bioorg Med Chem Lett 2009; 19: 5325-5328
  • 24 Kamath PR, Sunil D, Ajees AA. et al. N0-((2-(6-bromo-2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene) benzohydrazide as a probable Bcl-2/Bcl-xL inhibitor with apoptotic and anti-metastatic potential. Eur J Med Chem 2016; 120: 134-147
  • 25 Kumar V, Basavarajaswamy G, Rai MV. et al. Rapid ‘one-pot’ synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents. Bioorg Med Chem Lett 2015; 25: 1420-1426
  • 26 Nagender P, Kumar RN, Reddy GM. et al. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents. Bioorg Med Chem Lett 2016; 26: 4427-4432
  • 27 Kolb J, Beck B, Domling A. Simultaneous assembly of the β-lactam and thiazole moiety by a new multicomponent reaction. Tetrahedron Lett 2002; 43: 6897-6901
  • 28 Oliveira RBD, Fagundes EMS, Soares RPP. et al. Synthesis and antimalarial activity of semicarbazone and thiosemicarbazone derivatives. Eur J Med Chem 2008; 43: 1983-1988
  • 29 Kumar P, Chandak N, Kaushik P. et al. Synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory–antibacterial agents. Med Chem Res 2012; 21: 3396-3405
  • 30 Kumaran RA, Sundararajan R, Kumar SV. et al. Solvent free synthesis, spectral correlation and antimicrobial activities of some 2E 40 –nitro chalcones. J Saudi Chem Soc DOI: 10.1016/j.jscs.2012.09.006.
  • 31 Janaki P, Sekar KG, Thirunarayanan G. Solvent-free one-pot cyclization and acetylation of chalcones: Synthesis of some 1-acetyl pyrazoles and spectral correlations of 1-(3-(3,4-dimethylphenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazole-1-yl) ethanones. J Saudi Chem Soc DOI: 10.1016/j.jscs.2012.11.013.
  • 32 Sakthinathan SP, Vanangamudi G, Thirunarayanan G. Synthesis, spectral studies and antimicrobial activities of some 2-naphthyl pyrazoline derivatives. Solid fly-ash: PTS catalyzed green aldol condensation: Synthesis, spectral correlation, antimicrobial and insect antifeedant potent of some aryl chalcones. Spectrochim Acta 2012; 95: 693-700
  • 33 Sundararajan R, Kumaran RA, Kumar SV. et al. Solid fly-ash: PTS catalyzed green aldol condensation: Synthesis, spectral correlation, antimicrobial and insect antifeedant potent of some aryl chalcones. Int J Pharm Chem Sci 2012; 4: 1657-1677
  • 34 Thirunarayanan G, Mayavel P, Thirumurthy K. et al. Eco-friendly synthesis and spectral correlations in some 1-phenyl-3-(5-bromothiophen-2-yl)-5-(substituted phenyl)-2-pyrazolines. Eur Chem Bull 2013; 2: 598-605
  • 35 Thirunarayanan G. Spectral correlation, antimicrobial and insect antifeedant activities of some 1-naphthyl keto-oxiranes. J Saudi Chem Soc 2014; 18: 854-863
  • 36 Swain CG, Lupton Jr. EC. Field and ressonance components of substituent effects. J Am Chem Soc 1968; 90: 4328-4337
  • 37 Thirunarayanan G, Sekar KG. Solvent-free one-pot cyclization and acetylation of chalcones: Synthesis of some 1-acetyl pyrazoles and spectral correlations of 1-(3-(3,4-dimethylphenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazole-1-yl) ethanones. J Saudi Chem Soc 2016; 20: 661-672
  • 38 Bhardwaj JK, Saraf P. Granulosa cell apoptosis by impairing antioxidant defense system and cellular integrity in caprine antral follicles post malathion exposure. Environ Toxicol 2016; 31: 1944-1954
  • 39 Bhardwaj JK, Saraf P. N-acetyl cysteine-mediated effective attenuation of methoxychlor-induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary. Environ Toxicol 2017; 32: 156-166