Novel Piperine-carboximidamide Hybrids: Design, Synthesis, and Antiproliferative Activity Via a Multi-targeted Inhibitory Pathway

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Dec 1

PMID 36453023

Authors

Lamya H Al-Wahaibi

Mohamed A Mahmoud

Yaser A Mostafa

Ali E Raslan

Bahaa G M Youssif

Affiliations

Soon will be listed here.

Abstract

A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids , , , , and have the highest antiproliferative activity. Compounds , , , , and inhibited EGFR with IC values ranging from 96 to 127 nM. Compounds and had the most potent inhibitory activity as BRAF (IC = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI = 44 and 35 nM against four cancer cell lines, respectively). Compound , the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, , , and have a high capacity to inhibit LOX-IMVI cell line survival.

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