Development of drugs that are selectively toxic to
cancer cells and safe to normal cells is crucial in
cancer treatment. Evaluation of membrane permeability is a key metric for successful
drug development. In this study, we have used in silico molecular models of
lipid bilayers to explore the effect of
phosphatidylserine (PS) exposure in
cancer cells on membrane permeation of natural compounds
Withaferin A (Wi-A),
Withanone (Wi-N),
Caffeic Acid Phenethyl Ester (CAPE) and
Artepillin C (
ARC). Molecular dynamics simulations were performed to compute permeability coefficients. The results indicated that the exposure of PS in
cancer cell membranes facilitated the permeation of Wi-A, Wi-N and CAPE through a
cancer cell membrane when compared to a normal cell membrane. In the case of
ARC, PS exposure did not have a notable influence on its permeability coefficient. The presented data demonstrated the potential of PS exposure-based models for studying
cancer cell selectivity of drugs.