Exploring binding potential of two new indole alkaloids from <i>Nauclea officinalis</i> against third and fourth generation EGFR: druglikeness, <i>in silico</i> ADMET, docking, DFT, molecular dynamics simulation, and MMGBSA study
Sanket Rathod, Sonali Shinde, Prafulla B. Choudhari, Aniket P. Sarkate, Somdatta Y. Chaudhari, Aarti Vijayakumar Shingan
Abstract
against third and fourth-generation EGFR mutations using computational tools. Through ADMET profiling, druglikeness prediction, docking, and simulations, we assessed their pharmacokinetics, binding interactions, and stability. Promising druglikeness and binding affinity were observed, particularly for (±)-19-O-butylangustoline, which demonstrated stronger binding against both EGFR mutants. MD simulations confirmed stable interactions, with (±)-19-O-butylangustoline exhibiting the highest stability. These findings highlight these indole alkaloids as potential anti-cancer agents, with (±)-19-O-butylangustoline warranting further optimisation for therapeutic development. This study informs their potential through insights into molecular properties and binding energetics.