Chemoprofiling and insilico prioritization of bioactive compounds from Laetiporus versisporus (Lloyd) Imazeki reveals potential Bcl-2 inhibitor

Laetiporus versisporus (Lloyd) Imazeki is an edible mushroom that grows abundantly in kodaikanal hills (India) during rainy season. Till now, there is a dearth of reports on chemoprofile and anticancer potential of this mushroom. In our recent study, L.versisporus ethanolic extract was reported to confer hepato-protective activity against DEN-induced HCC rats and also found to downregulate Bcl-2 activity. Moreover, the phytocompounds of a related species namely, L. sulphurous is also reported to potentially modulate Bcl-2 in glioblastoma. Hence, by this study, the bioactive compounds from L. versisporus ethanolic extract were profiled using LC-MS analysis and were virtually screened against ligand binding site of Bcl-2 in order to predict potential moieties with anticancer efficacies. Further, the top 3 potential hits were shortlisted based on MMGBSA score, ADME properties and stable complex formation during MD simulation. Amongst these hits, (6S)-1alpha, 25-dihydroxy vitaminD36,19-sulfurdioxide adduct was found to be highly promising in terms of binding affinity and ADME features comparable to the known inhibitor (DRO), thus shall be further probed for therapeutic efficacy using experimental validations for effective and natural mode of combating Bcl-2 mediated cancers. Communicated by Ramaswamy H. Sarma

Automated summary

Laetiporus versisporus is an edible mushroom that grows in the rainy season in the kodaikanal hills of India. Its ethanolic extract has shown hepatoprotective activity and the ability to downregulate Bcl-2 activity. Through LC-MS analysis and virtual screening, bioactive compounds from the extract were identified and their potential binding to Bcl-2 was predicted. One compound was found to be highly promising and will be further investigated through experimental validations.