title: Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives.
abstract: In the present study, 7-subsituted coumarin derivatives were synthesized using various aromatic and heterocyclic amines, and evaluated in vivo for anti-inflammatory and analgesic activity, and for ulcerogenic risk. The most active compounds were evaluated in vitro for 5-lipoxygenase (5-LOX) inhibition. Docking study was performed to predict the binding affinity, and orientation at the active site of the enzyme. In vivo anti-inflammatory and analgesic activity, and in vitro 5-LOX enzyme inhibition study revealed that compound 33 and 35 are the most potent compounds in all the screening methods. In vitro kinetic study of 35 showed mixed or non-competitive type of inhibition with 5-LOX enzyme. Presence of OCH3 group in 35 and Cl in 33 at C6-position of benzothiazole ring were found very important substitutions for potent activity.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Pavan
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Vyas
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Bhavesh
authors.initials: B
authors.lastname: Variya
authors.affiliation: Institute of Science, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Palak
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Gulamnizami
authors.initials: G
authors.lastname: Qureshi
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India. Electronic address: ghate72@gmail.com.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ghate
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002351:Carrageenan; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D051381:Rats; D013276:Stomach Ulcer / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003374:Coumarins; D016859:Lipoxygenase Inhibitors; D002351:Carrageenan; D001094:Arachidonate 5-Lipoxygenase
keywords: 5-Lipoxygenase inhibitors; 7-Substituted coumarins; Anti-inflammatory and analgesic agents; Docking