Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non‐small cell lung cancer using network pharmacology and validation through molecular docking

Abstract

IntroductionAzadirachta indica A. Juss. is a well‐known medicinal plant that has been used traditionally to cure various ailments in every corner of the globe. There are many in vitro and in vivo experimental evidences in connection with the bioactivity of the extracts of this plant. Lung cancer is the deadliest form of cancer and contributes to the most cancer related deaths. The mode of action of anticancer components of this plant is still to be established explicitly.ObjectiveThe objective of this study is to identify druggable targets of active constituents of A. indica A. Juss. for non‐small cell lung cancer (NSCLC) using network pharmacology and validation of activity through molecular docking analysis.MethodologyTargets of all the active phytochemicals from A. indica were predicted and genes related to NSCLC were retrieved. A protein–protein interaction (PPI) network of the overlapping genes were prepared. Various databases and servers were employed to analyse the disease pathway enrichment analysis of the clustered genes. Validation of the gene/protein activity was achieved by performing molecular docking, and ADMET profiling of selected phytocompounds was performed.ResultGene networking revealed three key target genes as EGFR, BRAF and PIK3CA against NSCLC by the active components of A. indica. Molecular docking and ADMET analysis further validated that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin and vepinin are the best suited anti‐ NSCLC among all the phytocompounds present in this plant.ConclusionThe present study has provided a better understanding of the pharmacological effects of active components from A. indica and its potential therapeutic effect on NSCLC.

Limonoids from neem (Azadirachta indica A. Juss.) are potential anticancer drug candidates

“…44 It is noteworthy that nimbolide, a covalent recruiter of the E3 ubiquitin ligase RNF114, can be used for targeted protein degradation that can be exploited for degrading therapeutically important targets, such as the BCR-ABL fusion oncogene. 161 Recently, Nath et al 162 identified EGFR, BRAF, and PIK3CA as druggable targets of neem for NSCLC using network pharmacology. Validation by molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling revealed that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin, and vepinin are the most active neem limonoids against NSCLC.…”