Identification of promising cancer target proteins of major sesquiterpene lactones from Vernonia spp

The potential sesquiterpene lactone groups from the Vernonia genus; namely vernolide-A, vernolide-B, and vernodalin, have been reported for anticancer effects by downregulating cancer promoter proteins. Nevertheless, prior investigations have failed to identify the target proteins that are associated with the compounds’ actions. Subsequently, the present investigation attempts to identify the target proteins associated with cancer. The number of candidate target proteins predicted by our molecular docking study for vernolide-A, vernolide-B, and vernodalin were one, five, and seven, respectively. Vernolide-A, vernolide-B, and vernodalin were predicted to have the most selective and attractive interactions with candidate target proteins; such as p38α, PGEP2R, and HSP90α, respectively. In addition, our MD simulation study revealed that the compounds’ effects on the residual flexibility were not substantial. This suggested that their relative binding-free energy was similar to that of well-established ligands; including PD169316, dinoprostone, and Pu-H54. We also addressed the potential molecular mechanisms that may be associated with compounds in this report. Vernolide-A, vernolide-B, and vernodalin may potentially inhibit the proliferation, survival, angiogenesis, and migration of cancer cells through their strong affinity for a variety of cancer-related molecules. Additional laboratory experimental designs; including in vitro and in vivo studies, are suggested to further our computational findings.