Theoretical studies on the structures and properties of combretastatin A-4 and its five-membered heterocyclic structural analogs

A series of novel Combretastatin A-4 analogs were derived by substituting an ethylene bridge with a five-membered heterocyclic ring. The structure and activity of the analogs were predicted by calculation, which helps find new lead compounds. The geometrical structure, infrared, ultraviolet–visible, nuclear magnetic resonance, and molecular electrostatic potential (ESP) of stilbene compound Combretastatin A-4 and its structural analogs were calculated and compared by density functional theory ωB97XD/6-311++G (2d, p) method. Conceptual density functional theory analyzed the global reaction descriptor. The condensed Fukui function was introduced to describe the reactivity of each atom in the molecule. The global reactivity descriptor predicted that compound w13 was stable and highly reactive. The pharmacokinetic analysis showed that compounds 38 and 40 may have strong genotoxicity and cardiotoxicity. Molecular docking showed that nitrogen or oxygen atoms easily form hydrogen bonds. Compounds w4 and w13 have stronger binding strength with 1SA0. The compound w13 might exert excellent antitumor activity, and its pharmacokinetic prediction results showed high safety, which is valuable for further experimental research.

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