Prabhu, DJ and Ray, U and Rajeev, A and Joy, R and George, AT and George, J and Raghavan, SC and John, F (2023) Design and Synthesis of Ketenimine Sulfonamide Conjugates through Multicomponent Reactions; A Combined Cytotoxic Analysis and Computational Exploration. In: ACS Omega, 8 (41). pp. 38619-38631.
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Abstract
Multicomponent reactions involving zwitterion generated from dimethyl acetylenedicarboxylate, aryl sulfonamide, and isocyanide to generate sulfonamide-conjugated ketenimines is reported. The synthetic strategy adopted is highly atom economical and stereoselective. Ketenimine sulfonamide analogues are key intermediates for further synthetic conversions to generate a combinatorial library of compounds. Furthermore, sulfonamide compounds are known to possess a broad spectrum of biological applications. All the novel molecules synthesized exhibit the potential to target the nonhomologous DNA end-joining (NHEJ) pathway with cytotoxic ability. Computational studies compliment the in vitro biological assays of the 8 small-molecule inhibitors. DNA double-strand breaks (DSBs) are considered as the most lethal among different DNA damages. NHEJ repairs about 70 of the DSBs generated in cells within mammals. The DNA-dependent protein kinase catalytic subunit is one of the PI3 kinases associated with NHEJ. Compounds DK01-DK08 were investigated for their ability to induce cancer cell death by treating with two leukemic cell lines where NHEJ is high. Results showed that bromoaryl (DK04)- and nitroaryl (DK05)-conjugated molecules showed excellent biological activity, having IC50 values of �2 μM in Nalm6 cell lines. © 2023 The Authors. Published by American Chemical Society.
| Item Type: | Journal Article |
|---|---|
| Publication: | ACS Omega |
| Publisher: | American Chemical Society |
| Additional Information: | The copyright for this article belongs to Author. |
| Department/Centre: | Division of Biological Sciences > Biochemistry |
| Date Deposited: | 04 Mar 2024 09:27 |
| Last Modified: | 04 Mar 2024 09:27 |
| URI: | https://eprints.iisc.ac.in/id/eprint/84353 |
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