title: Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles.
abstract: Two series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H-pyran-2-ones (4a-4j) and pyrano[4,3-c]pyrazoles (6a-6e and 6g) were synthesized starting from 3-acetyl-4-chloro-6-methyl-2H-pyran-2-one (2). Estimation of pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side effects and interaction with drug-metabolizing enzymes were made for the synthesized compounds on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by PharmaExpert software. COX inhibition predicted by PASS was confirmed by experimental evaluation and validated via docking studies. Out of all the compounds, compounds 4h, 4j, 6e, 6g exhibited good anti-inflammatory activity, whereas compounds 4b, 4c, 4h, 4i, 4j, 6b, 6e, 6g showed excellent analgesic activity compared with standard drug Diclofenac sodium.
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136 119, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Poonam
authors.initials: P
authors.lastname: Lohan
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Aneja
authors.forename: Girish Kumar
authors.initials: GK
authors.lastname: Gupta
authors.forename: Dhirender
authors.initials: D
authors.lastname: Kaushik
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D019295:Computational Biology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007202:Indicators and Reagents / Q000633:toxicity; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D007202:Indicators and Reagents; D011720:Pyrazoles; D004008:Diclofenac; D002351:Carrageenan; D019342:Acetic Acid