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A novel class of human 15‐LOX‐1 inhibitors based on 3‐hydroxycoumarin
Author(s) -
Alavi Seyed Jamal,
Sadeghian Hamid,
Seyedi Seyed Mohammad,
Salimi Alireza,
Eshghi Hossein
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13174
Subject(s) - 4 hydroxycoumarin , class (philosophy) , chemistry , computational biology , pharmacology , combinatorial chemistry , stereochemistry , biochemistry , biology , computer science , artificial intelligence , catalysis
Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipo‐oxygenase 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 derivative demonstrated potent inhibitory activity and the compound, 5f , showed the best result. Radical scavenging assessment, IC 50 , HNMR, and DPPH bleaching results indicate that the electronic properties are the major factors for the lipo‐oxygenase inhibition potency of the synthetic coumarins. Based on the theoretical studies, it was suggested that the mesomeric effect of the substituent at the seventh position of the benzene ring is one of the major factors in the stability of the oxy‐radical intermediate.