Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Vishwanath, Divakar and Girimanchanaika, Swamy S. and Dukanya, Dukanya and Rangappa, Shobith and Yang, Ji-Rui and Pandey, Vijay and Lobie, Peter E. and Basappa, B. (2022) Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase. Molecules, 27 (3). ISSN 1420-3049

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Official URL: https://doi.org/10.3390/molecules27030703

Abstract

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC50 values in the range of 1.4 to 25 mu M. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC50 value of 1.4 mu M, when compared to Olaparib (IC50 = 3.2 mu M). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC50 values of 15.3 and 19.2 mu M, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.

Item Type: Article
Uncontrolled Keywords: oxadiazole; poly(ADP-ribose) polymerase; human breast cancer; nicotinamide
Subjects: C Chemical Science > Organic Chemistry
Divisions: Department of > Organic Chemistry
Depositing User: C Swapna Library Assistant
Date Deposited: 05 Sep 2023 10:18
Last Modified: 13 Sep 2023 10:05
URI: http://eprints.uni-mysore.ac.in/id/eprint/17729

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