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

Autor: Chavan PV; Department of Chemistry, Shivaji University, Kolhapur 416 004, India., Desai UV; Department of Chemistry, Shivaji University, Kolhapur 416 004, India. Electronic address: uvdchem2011@gmail.com., Wadgaonkar PP; Polymer Science and Engineering Division, CSIR, National Chemical Laboratory, Pune 411 008, India., Tapase SR; Biochemistry Division, Department of Chemistry, Savitribai Phule Pune University, Pune 411007, India., Kodam KM; Biochemistry Division, Department of Chemistry, Savitribai Phule Pune University, Pune 411007, India., Choudhari A; Combi - Chem. Bio-Resource Centre, CSIR National Chemical Laboratory, Pune 411 008, India., Sarkar D; Combi - Chem. Bio-Resource Centre, CSIR National Chemical Laboratory, Pune 411 008, India. Electronic address: d.sarkar@ncl.res.in.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Apr; Vol. 85, pp. 475-486. Date of Electronic Publication: 2019 Feb 08.
DOI: 10.1016/j.bioorg.2019.01.070
Abstrakt: 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, PANC-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 IC 50 values less than 10 μM. 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 (IC 50  = 2.13 μM and 4.80 μM, respectively). In case of MDA-MB-231, three compounds (6k, 6j and 6s) showed antiproliferative activity amongst which 6k was the most potent one (IC 50  = 3.78 μM). On the other hand, in cervical cancer HeLa cells, compounds 6b, 6g, 6s and 6u showed excellent antiproliferative activity (IC 50  = 4.05, 3.54, 3.83, 3.35 μM, 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 (IC 50  < 5 μM) suggested that these compounds induce cell death by apoptosis.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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