Synthesis, characterization and in vitro anticancer activity of C-5 curcumin analogues with potential to inhibit TNF-α-induced NF-κB activation.

Amit Anthwal,Bandana K Thakur,Bharat B Aggarwal,D S Rawat,M S M Rawat,Amit K Tyagi

doi:10.1155/2014/524161

Abstract

In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

Highlights

In the last few decades, importance has been given to biologically active natural products as these compounds generally do not have any side effects
Curcumin ability to inhibit the growth of various types of cancer cells at various stages of cancer progression is due to its potential to act on multiple targets [13,14,15,16,17]
In vivo and in vitro studies showed that curcumin undergo rapid metabolism by oxidation, reduction, glucuronidation, and sulfation [20, 21], which occur at 4-OH [22]

Summary

Introduction

In the last few decades, importance has been given to biologically active natural products as these compounds generally do not have any side effects The proof of this is the fact that more than 62% of the anticancer drugs approved from 1983 to 1994 are either natural products or natural product analogues [1]. In search of new molecules with good cytotoxicity against cancer cells we planned to synthesize new C-5 curcumin analogues and selected amido-ether linker for blocking 4-OH (Figure 1). As a part of our research work towards development of biologically important hybrid molecules [27], we designed new curcumin analogues. We report synthesis, theoretical prediction of physicochemical properties, cytotoxicity, and inhibition of TNF-α-induced NF-κB activation of C-5 curcumin analogues (3a–3p) in human cancer cell. Compounds were found to inhibit TNFα-induced NF-κB activation

Results and Discussion

Experimental Section

General Procedure for Synthesis of N-Phenyl and N-Benzyl

Assessment of Anti-Inflammatory Potential

Conclusion