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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Feb 15

PMID 35163965

Authors

Divakar Vishwanath

Swamy S Girimanchanaika

Dukanya Dukanya

Shobith Rangappa

Ji-Rui Yang

Vijay Pandey

Peter E Lobie

Basappa Basappa

Affiliations

Soon will be listed here.

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 IC values in the range of 1.4 to 25 µM. Furthermore, compound inhibited the viability of MCF-7 cells with an IC value of 1.4µM, when compared to Olaparib (IC = 3.2 µM). Compound also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds and produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds and 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 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.

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