Quantitative structure-activity relationship study of novel rhinacanthins and related naphthoquinone esters as anticancer agents

Abstract

The anticancer activity of rhinacanthins and related naphthoquinone esters is quantitatively analyzed through Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory actions of these compounds. From both approaches it appeared that naphthalene ring instead of benzene ring, dimethyl substitution at R₁ and R₂, and hydrogen-bond acceptor substituents at R₃ (Figure ) are advantageous to improve the activity of a compound against KB cell lines. This in turn leads to the suggestion that the rhinacanthin-N scaffold is the structural entity that needs exploration for new potential compounds. Further, in the Fujita-Ban analysis, it is observed that the compounds bearing a OMe substitution, relative to H, at R₄ have a slight positive contribution to pIC₅₀ (KB) whereas the substituents H or OMe at R₅, relative to OH, have negative contributions. In conformity with these findings, the Hansch approach revealed that a more hydrophobic group at R₄ and a more hydrophilic group at R₅ positions are beneficial in raising the activity. The two quantitative structure-activity relationship (QSAR) analyses, differing in parametric approach, therefore, provided the grounds for rationalizing the substituent selection to design more potent compounds of the series.

Figure 1 Structures of rhinacanthin–M (1), –N (14), –Q (15) and related naphthoquinone esters (2–13, 16–42).

Keywords::

• Rhinacanthins and Naphthoquinone Esters
• QSAR analysis
• Fujita-Ban and Hansch approaches
• Physicochemical properties
• anticancer agents

Acknowledgements

We are thankful to the Department of Chemistry, S. K. Government College and Department of Engineering Chemistry, Sobhasaria Engineering College, Sikar for providing the facilities to complete this work.