Design and Development of Hybrid Inhibitor to Synchronously Act on Four Biochemically Distinct Target for Suppression of Tumor Growth in Synergistic Manner.

Posted: 11 Feb 2020

Date Written: February 6, 2020

Abstract

Abstract: Cancer is a generic term for a large group of disorder that can affect any part of the body. Conventionally, anticancer agents designed to hit single biological targets have been the main approach in therapeutics development, but these drugs often have limited clinical utility. To explore this, we have proposed a novel strategy with a single molecule designed to synchronously act on four biochemically distinct target such as HDAC, TACE, EGFR and HER2. The concurrent blockade of HDAC, TACE and RTK pathways represents a novel approach to cancer therapy and may provide high efficacy and overcome limitations in the treatment of certain cancers.

A series of novel-substituted hydroxamic acid analogs were synthesized and evaluated for anticancer activity against MCF-7, MDA-MB-231, IMR-32 and HT-29 cancer cell lines. The synthesized derivatives show good anticancer activity as compared to standard. Western blot analysis was performed on selected compound earn the desired results. The study also suggests that these analogs can serve as better therapeutic agents against cancer and can provide starting point for building more potent analogs in future.

Molecular modeling studies of synthesized series includes QSAR, Docking and ADME properties of target compounds were analysed using Schrodinger software v11.6. The synthesized derivatives shows good binding interaction with the respective receptor.

Keywords: HDAC, EGFR, TACE, HER2, Molecular Modeling

JEL Classification: I23

Suggested Citation

Dhawale, Sachin and Mokale, Santosh, Design and Development of Hybrid Inhibitor to Synchronously Act on Four Biochemically Distinct Target for Suppression of Tumor Growth in Synergistic Manner. (February 6, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3533273

Santosh Mokale

Independent ( email )

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