Synthesis, biological evaluation, and molecular docking studies of N-(α-acetamido cinnamoyl) aryl hydrazone derivatives as antiinflammatory and analgesic agents
- 334 Downloads
A series of acyl hydrazone derivatives were synthesized and screened for antiinflammatory and analgesic activities. The N-acylarylhydrazone compounds described herein were designed by combining the pharmacophoric features of hydrazones and styryl ketones in order to identify the pharmacophoric contribution of the N-acylarylhydrazone moiety and to study the structure–activity relationships. In carrageenan-induced paw edema test, N′-(4-hydroxy benzylidene)-2-acetamido-3-phenyl propenohydrazide (6j) reduced edema by 74 % which is comparable to the standard reference drug, phenylbutazone at equidose. N′-(4-methoxy benzylidene)-2-acetamido-3-phenyl propenohydrazide (6g) showed analgesic activity (68 %) which is equipotent to the standard drug, aspirin (64 %). Molecular docking studies further confirmed that 6j showed better binding affinity with COX-2 and LOX-5 with reduced gastric ulcerogenic effect when compared to phenylbutazone.
KeywordsHydrazone Antiinflammatory Analgesic Molecular docking
The authors are thankful to Indian Institute of Chemical Technology, Hyderabad for providing spectral data and AU and DB are thankful to DBT, Ministry of Science and Technology, Govt. of india for supporting reasearch at SVIMS University Tirupati through BIF program (No. BT/BI/25/001/2006).
Conflict of interest
The authors report no conflict of interest.
- Almasirad A, Tajik M, Bakhtiari D, Shafiee A, Abdollahi M, Zamani MJ, Khorasani R, Esmaily H (2005) Synthesis and analgesic activity of N-aryl hydrazone derivatives of mefenamic acid. J Pharm Pharmaceut Sci 8:419–425Google Scholar
- Delano WL (2005) PYMOL. DeLano Scientific LLC, USAGoogle Scholar
- Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK, Shaw DE, Francis P, Shenkin PS (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749. doi: 10.1021/jm0306430 CrossRefPubMedGoogle Scholar
- Koster R, Anderson M, De Beer EJ (1959) Acetic acid for analgesic screening. Science 62:1986–1989Google Scholar
- Maruthikumar TV, Rao PH (2005) A novel synthesis of 1-(1-aza-2-arylvinyl)-2 [(1E)-2 aryl vinyl]-4 (phenyl methylene)-2-imidazolin-5-ones. Indian J Chem 44B:1497–1499Google Scholar
- Potluri V, Pradhan D, Umamaheswari A (2011) Virtual screening of human MEK1 protein inhibitors catechin and gw8510. Onl J Bioinform 12:98–106Google Scholar
- Priyadarshini V, Pradhan D, Munikumar M, Umamaheswari A (2011) Homology modeling and active site analysis of MurB Reductase : a potential drug target of Legionella pneumophila. Onl J Bioinform 12:217–229Google Scholar