تهیه بعضی مشتقات ایمیدازوپیریدین ایندول به عنوان عوامل ضد سرطان: سنتز چند جزیی تک مرحله، ارزیابی بیولوژیک و مطالعات داکینگ مولکولی

باخرد, زهره and صفوی, ملیحه and سپهری, ساقی and فصیحی, افشین and صادقی علی آبادی, حجت and باخرد, محمد and رستگار, حسین and لاریجانی, باقر and سقایی, لطف الله and مهدوی, محمد (1398) تهیه بعضی مشتقات ایمیدازوپیریدین ایندول به عنوان عوامل ضد سرطان: سنتز چند جزیی تک مرحله، ارزیابی بیولوژیک و مطالعات داکینگ مولکولی. Research on Chemical Intermediates ــ 45 (10). pp. 5261-5291. شاپا 0922-6168

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Official URL: https://link.springer.com/article/10.1007/s11164-0...


Preparation of some novel imidazopyridine derivatives of indole as anticancer agents: one‑pot multicomponent synthesis, biological evaluation and docking studies

English Abstract

A series of novel imidazopyridine derivatives of indole has been synthesized. All the synthesized derivatives were evaluated for their antiproliferative activity against A-549, T-47D, Hep-G2 and MCF-7 human cancer cell lines. The results demonstrated that some of these derivatives exhibited moderate to excellent cytotoxic activities. Compounds 7a having a cyclohexyl ring substituted to the second amine of imidazopyridyl moiety and phenyl ring of the C-2 indole ring and 7f with a para-methylphenyl ring at the same position exhibited the highest activity against the A-594 cell line with IC50 of 11.48 μM and 10.66 μM, respectively. The results indicate that compounds 7a and 7f are more cytotoxic towards cancer cell lines compared with etoposide in vitro. In addition, compounds, 7d and 7j showed the most potent activity against Hep-G2, equal to etoposide as the standard drug. Also, most of the compounds were inactive against the T-47D and MCF-7 cell lines. The morphological analysis by the acridine orange/ethidium bromide double-staining test and flow cytometry analysis indicated that compounds 7a and 7f induced apoptosis in A-549 cells. Furthermore, in silico and in vitro results of the synthesized compounds showed good correlation with each other. Molecular docking results of the compounds of the 7a–k series with the cyclohexyl ring substituted to the second amine of the imidazopyridyl moiety compared with the 7l–t members with the t-butyl group at the same position confirmed the effect of the higher lipophilicity on hydrophobic interactions with the studied enzymes. Moreover, all the compounds showed higher affinity to tubulin than topoisomerase IIα enzyme.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :زهره باخرد
نویسنده :ملیحه صفوی
نویسنده :ساقی سپهری
نویسنده :افشین فصیحی
نویسنده :حجت صادقی علی آبادی
نویسنده :محمد باخرد
نویسنده :حسین رستگار
نویسنده :باقر لاریجانی
نویسنده مسئول :لطف الله سقایی
نویسنده مسئول :محمد مهدوی
Additional Information:Impact Factor 2.064 Indexed in: ISI(Science Citation Index, Science Citation Index Expanded) , SCOPUS, Google Scholar, Current Chemical Reactions, Current Contents/Physical, EBSCO
Uncontrolled Keywords:عوامل ضد سرطان، داکینگ مولکولی، سنتز تک مرحله، حلقه ایمیدازول
کلیدواژه ها (انگلیسی):Anticancer agents · Molecular docking · One-pot synthesis · Imidazopyridine ring
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:12214
Deposited By: ساقی سپهری
Deposited On:15 Jul 1398 11:59
Last Modified:15 Jul 1398 11:59

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