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Lapachol is a proven anticancer medication ingredient that has been removed from the market due to its toxicity, but cannot disregard its therapeutic properties. Aiming to search for potent anticancer derivative of lapachol with a harmless impact, a series of novel isoxazoles derivatives were synthesized by its chemical modification. Alkylation of the hydroxyl group of lapachol gave its propargyl ether which, via copper-catalyzed cycloaddition (CuAAC) click chemistry with different oximes, afforded naphthoquinonolyl isoxazole derivatives. Molecular docking study of lapachol and its newly synthesized derivatives was also performed for potential inhibitory action toward PKM2 enzyme. All compounds showed good docking results. Among these synthesized lapachol derivatives, compound 7c showed the highest binding affinity and followed all drug rules. These findings indicated that the introduction of isoxazole fragment to the lapachol may have a significant impact on pyruvate levels in cancer cells and provides further directions for future research to find new lapachol analogues suitable for cancer treatment. [ABSTRACT FROM AUTHOR]

Chemical investigation of the chloroform extract of heartwood of Tectona grandis L. f. led to the isolation of three new naphthoquinone derivatives, tectonaquinones A (1), B (2) and C (3), along with six known compounds: barleriaquinone-I (4), tectoquinone (5), tecomaquinone I (6), lapachol (7), obtusifolin (8) and 2-hydroxy-3-methyl anthraquinone (9). The structures of the new compounds were elucidated by spectroscopic methods including 2 D NMR experiments. Tectonaquinone B is the first natural compound that has a hexa-cyclic dinaphthofuran-dione scaffold. Tectonaquinone C has a bicyclic acetal motif that is unusual in nature. [ABSTRACT FROM AUTHOR]