A novel class of human 15-LOX-1 inhibitors based on 3-hydroxycoumarin

Abstract

Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipoxygenase enzymes. Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin (7-M3HC) derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result. Radical scavenging assessment, IC₅₀, HNMR, and DPPH bleaching results indicate that the electronic properties are the major factors for the lipoxygenase inhibition potency of the synthetic coumarins. Based on the theoretical studies, it was suggested that the mesomeric effect of the substituent at the 7th position of the benzene ring is one of the major factors in the stability of the oxy radical intermediate.

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In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin (7-M3HC) derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result

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