Structure-based molecular networking, molecular docking, dynamics simulation and pharmacokinetic studies of Olax subscorpioideafor identification of potential inhibitors against selected cancer targets

AbstractThe rationale at the basis of targeted approach in oncology is radically shifting—from development of highly specific agents aiming at a single target towards molecules interfering with multiple targets. This study was performed to isolate and characterize bioactive molecules from Olax subscorpioideastem and investigate their potentials as multi-targeted inhibitors against selected non-small cell lung cancer, breast cancer and chronic myelogenous leukemia oncogenic targets. Three compounds: β-sitosterol (1), α-amyrin (2) and stigmasterol (3) were isolated. The structures of 1 − 3 were elucidated by analysis of their spectroscopic data (NMR, MS and IR). To the best of our knowledge, this is the first time these compounds were isolated from O. subscorpioideastems. Furthermore, integrated analysis of MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) workflow enabled dereplication and identification of 26 compounds, including alkaloids (remerine, boldine), terpenoids (3-hydroxy-11-ursen-28,13-olide, oleanolic acid), flavonoids (kaempferitrin, olax chalcone A) and saponins in O. subscorpioideastem. Molecular docking studies revealed that some of the compounds, including olax chalcone A (–9.2 to −10.9 kcal/mol), 3-Hydroxy-11-ursen-28,13-olide (–6.6 to −10.2 kcal/mol), α-amyrin (–6.6 to −10.2 kcal/mol), stigmasterol (–7.7 to −10.1 kcal/mol), β-Sitosterol (–7 to −9.9 kcal/mol) and kaempferitrin (–7.7 to −9 kcal/mol) possessed good inhibitory potentials against selected cancer targets, when compared with reference inhibitors (–8.4 to −13.7 kcal/mol). A few of these compounds were shown to have considerable to favorable pharmacokinetic and drug-likeness properties. This study provides some rationale for the use of O. subscorpioideain ethnomedicinal management of cancer and identifies some potential anticancer agents.Communicated by Ramaswamy H. Sarma