1. Organocatalyzed umpolung addition for synthesis of heterocyclic-fused arylidene-imidazolones as anticancer agents.
- Author
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Kumar G, Das C, Acharya A, Bhal S, Joshi M, Kundu CN, Choudhury AR, and Guchhait SK
- Subjects
- Apoptosis, Cell Line, Tumor, Cell Proliferation, Drug Screening Assays, Antitumor, Imidazoles chemistry, Imidazoles pharmacology, Molecular Structure, Structure-Activity Relationship, Antineoplastic Agents chemistry
- Abstract
A strategy of "Nature-to-new" with iterative scaffold-hopping was considered for investigation of privileged ring/functional motif-elaborated analogs of natural aurones. An organocatalyzed umpolung chemistry based method was established for molecular-diversity feasible synthesis of title class of chemotypes i.e. (Z)-2-Arylideneimidazo[1,2-a]pyridinones and (Z)-2-Arylidenebenzo[d]imidazo[2,1-b]thiazol-3-ones. Various biophysical experiments indicated their important biological properties. The analogs showed characteristic anticancer activities with efficiency more than an anticancer drug. The compounds induced apoptosis with arrest in the S phase of the cell cycle regulation. The compounds' significant effect in up/down-regulation of various apoptotic proteins, an apoptosis cascade, and the inhibition of topoisomerases-mediated DNA relaxation process was identified. The analysis of the structure-activity relationship, interference with biological events and the drug-likeness physicochemical properties of the compounds in the acceptable window indicated distinctive medicinal molecule-to-properties of the investigated chemotypes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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