Alkyne-azide Cycloaddition Analogues of Dehydrozingerone As Potential Anti-prostate Cancer Inhibitors the PI3K/Akt/NF-kB Pathway

Overview

Journal Medchemcomm

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2018 Aug 16

PMID 30108729

Citations 8

Authors

Chetan Kumar

Reyaz Ur Rasool

Zainab Iqra

Yedukondalu Nalli

Prabhu Dutt

Naresh K Satti

Neha Sharma

Sumit G Gandhi

Anindya Goswami

Asif Ali

Affiliations

Soon will be listed here.

Abstract

Herein, we report the isolation and synthetic modification of dehydrozingerone (DHZ, ), a secondary metabolite present in the rhizome of . We synthesized -propargylated dehydrozingerone, which was subsequently coupled by alkyne-azide cycloaddition () using click chemistry. The compounds () were evaluated for their cytotoxic activity in a panel of three cancer cell lines. Among all the DHZ derivatives, , , , , and displayed potent cytotoxic potential with an IC value ranging from 1.8-3.0 μM in MCF-7, PC-3 and HCT-116 cell lines. Furthermore, compound has proven to be the most potent cytotoxic compound in all the three distinct cancer cell lines and also demonstrated significant anti-invasive potential in prostate cancer. The mechanistic study of compound showed that it not only suppressed the AKT/mTOR signalling which regulates nuclear transcription factor-NF-kB but also augmented the expression of anti-invasive markers E-cadherin and TIMP. Compound significantly decreased the expression of pro-invasive markers vimentin, MMP-2 and MMP-9, respectively. This study underscores an efficient synthetic approach employed to evaluate the structure-activity relationship of dehydrozingerone () in search of potential new anticancer agents.

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