Chaitanya, M. and Babajan, B. and Madhusudana, P. and Anuradha, C.M. and Rao, R.M. and Prakash, N.R. and Manna, S.K. and Naveen, M. and Kumar, C.S. (2013) Synthesis and evaluation of resveratrol derivatives as new chemical entities for cancer. Journal of Molecular Graphics and Modelling, 41. pp. 43-54. ISSN 1093-3263

Text J Mol Graphics Model 41 p43.pdf Restricted to Repository staff only Download (2253Kb) | Request a copy

Abstract

Resveratrol has been shown to be active in inhibiting multistage carcinogenesis. The potential use of resveratrol in cancer chemoprevention or chemotherapy settings has been hindered by its short half-life and low bioavailability. Considering the above remarks, using resveratrol as a prototype, we have synthesized two derivatives of resveratrol. Their activity was evaluated using in vitro and in silico analysis. Biological evaluation of resveratrol analogues on U937 cells had shown that two synthesized analogues of resveratrol had higher rates of inhibition than the parental molecule at 10μM concentration. EMSA conducted for NF-kB revealed that these molecules significantly interfered in the DNA binding ability of NF-kB. It was found that these molecules suppressed the expression of TNFα, TNFR, IL-8, actin and activated the expression of FasL, FasR genes. To understand possible molecular mechanism of the action we performed docking and dynamic studies, using NF-kB as a receptor. Results showed that resveratrol, RA1 and RA2 interacted with the residues involved in DNA binding. Resveratrol analogues by interacting NF-kB might have prevented its translocation and also by interacting with the residues involved in DNA binding might have prevented the binding of NF-kB to DNA. This may be the reason for suppression of NF-kB binding to DNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Item Type:	Article
Depositing User:	Users 2 not found.
Date Deposited:	14 Sep 2015 09:07
Last Modified:	14 Sep 2015 09:07
URI:	http://cdfd.sciencecentral.in/id/eprint/506

Actions (login required)

View Item