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Synthesis, biological evaluation, and molecular docking studies of N-(α-acetamido cinnamoyl) aryl hydrazone derivatives as antiinflammatory and analgesic agents

Abstract

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.

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Acknowledgments

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).

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The authors report no conflict of interest.

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Correspondence to Galla Rajitha.

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Rajitha, G., Prasad, K.V.S.R.G., Umamaheswari, A. et al. Synthesis, biological evaluation, and molecular docking studies of N-(α-acetamido cinnamoyl) aryl hydrazone derivatives as antiinflammatory and analgesic agents. Med Chem Res 23, 5204–5214 (2014). https://doi.org/10.1007/s00044-014-1091-0

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Keywords

  • Hydrazone
  • Antiinflammatory
  • Analgesic
  • Molecular docking