Identification of dual inhibitors for EGFR(T790M/C797S) and VEGFR-2 in Non-Small Cell Lung Cancer from Moringa oleifera derived phytochemicals: An In-silico Approach

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality on a global scale for both men and women. At present, the treatment of NSCLC involves the use of tyrosine kinase inhibitors (TKIs), which specifically target EGFR. However, resistance mechanisms like the emergence of T790M and C797S EGFR mutations and increased expression of VEGFR-2 often impede the efficacy of various generations of TKIs. Thus, EGFR and VEGFR-2 offer a great opportunity to treat NSCLC through the development of multi-targeted drugs. Our study aims to identify potential inhibitors by thoroughly evaluating the biological activity of M. oleifera -derived compounds that could serve as novel dual inhibitors of EGFR ^{(T790M/C797S)} and VEGFR-2, resulting in a synergistic inhibitory effect on these signaling pathways. We identified five potential phytocompounds from M. oleifera (hesperetin, gossypetin, quercetagetin, gallocatechin, and epigallocatechin) that showed significant binding affinity in virtual screening and multi-stage molecular docking analysis with remarkable drug-likeness and ADMET properties. These selected drug candidates also strongly bound and stayed stable with the receptors during the 200 ns MD simulation and MM-GBSA calculation. These findings indicate that these therapeutic candidates have the capacity to precisely target both EGFR and VEGFR-2 and can potentially act on both of these pathways as a single agent.