Synthesis and screening of novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines as antiproliferative and tubulin polymerization inhibitors

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dc.contributor.authorDwivedi, Ashish Ranjan
dc.contributor.authorRawat, Suraj Singh
dc.contributor.authorKumar, Vijay
dc.contributor.authorKumar, Naveen
dc.contributor.authorAnand, Piyush
dc.contributor.authorYadav, Ravi Prakash
dc.contributor.authorBaranwal, Somesh
dc.contributor.authorPrasad, Amit
dc.contributor.authorKumar, Vinod
dc.date.accessioned2024-01-21T10:26:43Z
dc.date.accessioned2024-08-13T11:19:32Z
dc.date.available2024-01-21T10:26:43Z
dc.date.available2024-08-13T11:19:32Z
dc.date.issued2022-08-28T00:00:00
dc.description.abstractColchicine binding site represent a crucial target for the anticancer drug development especially in view of emerging drug resistance from the currently available chemotherapeutics. A total of 16 novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines were synthesized and screened for antiproliferative and tubulin polymerization inhibition potential. The synthesized compounds were evaluated against MCF-7, HeLa and HT-29 cancer cell lines and normal cell line HEK-293 T. In the series, 2?aryl group with 4?bromophenyl substitution displayed IC50 values of 6.37 �M, 17.43 �M, 6.76 �M and 4?chlorophenyl substitution displayed IC50 values of 2.16 �M, 8.53 �M, 10.42 �M against MCF-7, HELA and HT29 cancer cell lines, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, both the lead compounds were found to induce mitochondria mediated apoptosis and lead molecule with 4?chlorophenyl substitution displayed significant tubulin polymerization inhibition activity. In the computation studies, lead molecule displayed significant binding affinites in the colchicine domain and showed good thermodynamic stability during 100 ns MD simulation studies. 4-N-Heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines showed appreciable drug like characteristics and can be developed as potent anticancer agents. � 2022 Elsevier Ltden_US
dc.identifier.doi10.1016/j.bmc.2022.116976
dc.identifier.issn9680896
dc.identifier.urihttp://10.2.3.109/handle/32116/3111
dc.identifier.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0968089622003698
dc.language.isoen_USen_US
dc.publisherElsevier Ltden_US
dc.subject6,7,8-Trimethoxyquinazolinesen_US
dc.subjectAnticanceren_US
dc.subjectAntiproliferativeen_US
dc.subjectCell cycleen_US
dc.subjectTubulin polymerization inhibitorsen_US
dc.titleSynthesis and screening of novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines as antiproliferative and tubulin polymerization inhibitorsen_US
dc.title.journalBioorganic and Medicinal Chemistryen_US
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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