SuperNatural inhibitors to reverse multidrug resistance emerged by ABCB1 transporter: Database mining, lipid-mediated molecular dynamics, and pharmacokinetics study.

ABSTRACT: An effective approach to reverse multidrug resistance (MDR) is P-glycoprotein (P-gp, ABCB1) transport inhibition. To identify such molecular regulators, the SuperNatural II database, which comprises > 326,000 compounds, was virtually screened for ABCB1 transporter inhibitors. The Lipinski rule was utilized to initially screen the SuperNatural II database, identifying 128,126 compounds. Those natural compounds were docked against the ABCB1 transporter, and those with docking scores less than zosuquidar (ZQU) inhibitor were subjected to molecular dynamics (MD) simulations. Based on MM-GBA binding energy (ΔGbinding) estimations, UMHSN00009999 and UMHSN00097206 demonstrated ΔGbinding values of -68.3 and -64.1 kcal/mol, respectively, compared to ZQU with a ΔGbinding value of -49.8 kcal/mol. For

SUBMITTER: Ibrahim MAA 

PROVIDER: S-EPMC10370898 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature