Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents

TitleClick chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents
Publication TypeJournal Article
Year of Publication2019
Authors,, ,, Wadgaonkar, PP, Tapase, SR, Kodam, KM, Choudhari, A, Sarkar, D
JournalBioorganic Chemistry
Volume85
Pagination475-486
Date PublishedAPR
Type of ArticleArticle
ISSN0045-2068
Keywords1, 2, 3-Triazolylspirochromenocarbazole, Anticancer, Apoptotic assay, Click chemistry, Cytotoxicity, heterogeneous catalysis, Multicomponent synthesis
Abstract

A series of spirochromenocarbazole tethered 1,2,3-triazoles were synthesized via click chemistry based one-pot, five component reaction between N-propargyl isatins, malononitrile, 4-hydroxycarbazole, aralkyl halides and sodium azide using cellulose supported CuI nanoparticles (Cell-CuI NPs) as the heterogeneous catalyst. Antiproliferative activity of all the synthesized compounds was investigated against panel of cancer cell lines such as MCF-7, MDA-MB-231, HeLa, PANG-1, A-549, and THP-1. Many of the synthesized compounds exhibited good anti-proliferative activity against breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cells with IC50 values less than 10 mu M. In case of MCF-7 cells, among the nine compounds that showed good anti-proliferative activity, compounds 6f and 6j were found to be highly potent (IC50 , = 2.13 mu M and 4.80 mu M, respectively). In case of MDA-MB-231, three compounds (6k, 6j and 6s) showed antiproliferative activity amongst which 6k was the most potent one (IC50 = 3.78 mu M). On the other hand, in cervical cancer HeLa cells, compounds 6b, 6g, 6s and 6u showed excellent antiproliferative activity (IC50 = 4.05, 3.54, 3.83, 3.35 mu M, respectively). All the compounds were found to be nontoxic to the human umbilical vein endothelial cells (HUVECs). AO and EtBr staining and fluorescence microscopy studies of the active compounds (IC50 < 5 mu M) suggested that these compounds induce cell death by apoptosis.

DOI10.1016/j.bioorg.2019.01.070
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

3.926

Divison category: 
Polymer Science & Engineering