In silico Assessment of Galanthamine Alkaloids as Cytotoxic Agents and Brd4 Inhibitors

Abstract

Cancer is associated with high mortality. The potential of Galanthamine alkaloids as cytotoxic agents and Brd4 inhibitors was investigated. Selected alkaloids were screened for cytotoxic properties using the Cell Line Cytotoxicity Predictor (CLCPred). The drug-likeness, physicochemical and pharmacokinetic properties of the compounds were determined using SwissADME. The interactions of the ligands with the Brd4 protein were investigated using SwissDock. Lastly, the toxicity of the compounds was investigated using SwissADME. The compounds showed cytotoxic potential against bone marrow neuroblastoma at Pa>0.5. All the compounds satisfied Lipinski’s, Verber’s, and Muegge’s conditions for drug-likeness. The binding energy of the alkaloids with Brd4 ranged between - 7.22 and - 7.82 kcal mol-1. Lycoramine with a binding energy of -7.82 kcal mol-1 had comparable binding energy to those of the standard drug, doxorubicin (-7.91 kcal mol-1), and Brd4 inhibitors: Pelabresib (-7.96 kcal mol-1) and Birabresib (-8.43 kcal mol-1). The compounds were non-AMES toxic, non-carcinogens, and weak inhibitors of the human ether-a-go-go related gene (hERG). Galanthamine alkaloids showed potential for treating human bone marrow neuroblastoma. The results of this study have laid a foundation for subsequent in vitro and in vivo studies to establish the predicted activity.