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

The 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 subscorpioidea stem 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: ß-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. subscorpioidea stems. 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. subscorpioidea stem. 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), ß-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. subscorpioidea in ethnomedicinal management of cancer and identifies some potential anticancer agents.Communicated by Ramaswamy H. Sarma.

Suppressive, curative, and prophylactic potentials of an antimalarial polyherbal mixture and its individual components in Plasmodium berghei-Infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains one of the most prevalent infectious diseases in tropical regions of the world, particularly in sub-Saharan Africa, where it remains epidemiologically holoendemic. The absence of effective vaccines and Plasmodium resistance to antimalarial drugs have been the major challenges to malaria control measures. An alternative strategy could be the application of validated and standardized herbal formulations. AIM OF THE STUDY: To evaluate the antimalarial activity of a polyherbal mixture (APM) and compare it to those of its individual constituent plants. METHODS: APM consisted of stem barks of Mangifera indica (MI), Azadirachta indica (AI), Nauclea latifolia (and roots, NL) and roots of Morinda lucida (ML). Dihydroartemisinin-piperaquine (DHP) and pyronaridine-artesunate (PA) served as positive controls. Antimalarial activity was evaluated using suppressive, curative and prophylactic assays in mice infected with Plasmodium berghei. RESULTS: All the herbal mixtures, individually and in combination, showed significant (p < 0.05) antiplasmodial activities in the various assays. They produced considerable parasite suppression (>50%), substantial clearance (>70%), and notable prophylaxis (>60%, except for NL: 35%). APM (95.4-98.7%) and AI (92%), respectively, elicited greater and comparable suppression relative to DHP (88%) and PA (87.3%). However, all the herbal decoctions, individually (72-93.6%) and in combination (82.5-91%), showed lower parasite clearance than DHP (100%) and PA (99.5%). Meanwhile, APM showed relatively greater suppression and prophylaxis than its constituent plants, suggesting that the combination produced synergistic or additive effects. CONCLUSION: These findings could substantiate the use of these plants, singly or in combination, as traditional remedies for malaria. Further studies are recommended to evaluate their clinical usefulness.