Abstract
The correlation between P-glycoprotein (Pgp) overexpression and multidrug resistance (MDR) in cancer is well-established. Recently, we identified (2-(4-methoxyphenyl)-4-quinolinyl) (2-piperidinyl)methanol (5) (NSC23925) as the most selective and potent MDR inhibitor. NSC23925 binds to Pgp, thus inhibiting its transporter function and reversing MDR in cancer cells. In order to further characterize the chemical properties and Pgp binding mode of the NSC23925 compound, we grew four NSC23925 crystal isomers (NSC23925a, NSC23925b, NSC23925c, and NSC23925d). These crystal isomers were first generated using a vapor diffusion growth technique before their precise structures were analyzed using X-ray crystallography. Functionally, the NSC23925a and NSC23925b isomers share a similar stabilization interaction of Cl− mediated hydrogen bonding. In contrast, in isomer NSC23925c, two Cl− are involved in the stabilization of adjacent molecules. In summary, these solved crystal structures may reveal the different activities of the four NSC23925 stereoisomers.
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•Four NSC23925 crystal isomers were first generated using a vapor diffusion growth technique.•The crystal structures of NSC23925 isomers were analyzed.•The solved NSC23925 crystal structures reveal potential Pgp binding sites.
