Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity.

In this article, we describe a set of subsequent five-steps chemical reactions to synthesize a ferrocene derivative named 1-(5-(diphenylphosphaneyl)cyclopenta-1,3-dien-1-yl)ethyl)imino)-1,3-dihydroisobenzofuran-5-yl)methanol (). Structural characterization of and its intermediate products was also performed and reported to attest to their formation. A molecular docking study was performed to propose the novel synthesized ferrocene derivative () as a potential antitumor candidate targeting the mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1. The computed docking score of () at -9.50 kcal/mol compared to the native anticancer staurosporine at -8.72 kcal/mol postulated a promising anticancer activity. Also, molecular dynamics (MD) simulations were carried out for 500 ns followed by MM-GBSA-binding free energy calculations for both the docked complexes of ferrocene and staurosporine to give more deep insights into their dynamic behavior in physiological conditions. Furthermore, DFT calculations were performed to unravel some of the physiochemical characteristics of the ferrocene derivative (). The quantum mechanics calculations shed the light on some of the structural and electrochemical configurations of () which would open the horizon for further investigation. HighlightsThe synthesis of a ferrocene derivative named 1-(5-(diphenylphosphaneyl)cyclopenta-1,3-dien-1-yl)ethyl)imino)-1,3-dihydroisobenzofuran-5-yl)methanol () was described.Structural characterizations of ferrocene derivative () and its intermediate products were also performed.DFT calculations, molecular docking, molecular dynamics, and MM-GBSA calculations were carried out.Computational studies revealed the antitumor potential of ferrocene derivative () through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma.