Anti-proliferative Activity of Some Oleanolic Acid Derivatives with Potent Topoisomerase Inhibitory Activity on B16 Melanoma Cells

Ahmed Ashour,Kuniyoshi Shimizu,Ryuichiro Kondo

doi:10.51850/wrj.2018.9.1.26-28

Abstract

Our previous study included the semisynthetic reactions on oleanolic acid, a common wood-derived oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid were synthesized based on docking studies and tested for their topoisomerase I and IIα inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C-13 and C-17. Some of these compounds act as dual inhibitors for both topoisomerase I and IIα giving new anticancer agents. The cytotoxic activity of these compounds on B16 melanoma cancer cells was evaluated. Results showed that most of these compounds have a higher cytotoxic activity on B16 melanoma cells.

Highlights

Molecular modeling systems provide powerful tools for building, visualizing, analyzing, and storing models of complex molecular systems that can help interpret structure activity relationship (Cohen et al 1990) where the techniques of combinatorial chemistry have revolutionized the development of active chemical leads where currently, instead of medicinal chemists making derivatives from scratch, a procedure is used whereby syntheses are based on combinatorial processes so that modification can be made in iterative fashion (Newman 2008)
Oleanolic acid which has been isolated from the unused parts of Hibiscus sabdariffa (Amer et al 2011) was suggested as backbone for rational design of specific topoisomerase inhibitors
From the results of B16 melanoma cell assay (Fig. 2), it was found that Compounds S5, S9 and S10 have a high cytotoxic activity

Summary

Introduction

Molecular modeling systems provide powerful tools for building, visualizing, analyzing, and storing models of complex molecular systems that can help interpret structure activity relationship (Cohen et al 1990) where the techniques of combinatorial chemistry have revolutionized the development of active chemical leads where currently, instead of medicinal chemists making derivatives from scratch, a procedure is used whereby syntheses are based on combinatorial processes so that modification can be made in iterative fashion (Newman 2008). Structure activity relationship suggested the general pentacyclic ring structure as important system for topoisomerase inhibitory activity. Oleanolic acid which has been isolated from the unused parts of Hibiscus sabdariffa (Amer et al 2011) was suggested as backbone for rational design of specific topoisomerase inhibitors.

Results

Conclusion