Abstract
Background: GTP-bound mutant forms of H-Ras (Harvey-Ras) proteins are found in almost 30% of human tumors. In the present in silico study, the inhibitory effect of different flavonoid compounds on mutant H-Ras protein p21 has been assessed. The inhibitory effect of flavonoids is compared with three known clinical anticancer drugs. Besides, these have been interacted with normal H-Ras and tumor necrosis factor (TNF) proteins for toxicity check. Results: Upon docking, it was found that flavonoids such as naringenin, daidzein, and hesperetin showed highest affinity (most negative Delta G), while rutin showed no affinity towards mutant H-Ras. The three clinical anticancer agents (erlotinib, letrozole and exemestane) showed binding energies in the range of -1.11 to -5.51 kcal/mol which is comparatively lower than the flavonoids indicating efficacy of flavonoids to prevent complex formation with Raf and thereby prevent downstream effects. However, flavonoids showed no interaction with normal H-Ras and TNF indicating little or no cytotoxicity. Conclusion: Our study demonstrates that flavonoids (naringenin, daidzein, and hesperetin) are effective drugs to inhibit complex formation between mutant H-Ras P21 and RBD of Raf. Copyright (C) 2010 S. Karger AG, Basel