Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis, antimicrobial evaluation and docking studies of new pyrazolone derivatives

Abdulsalam AM Alkhaldi¹, Mohamed A Abdelgawad^2,3

¹Department of Biology, College of Science, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; ²Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; ³Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, 4Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526 Egypt.

For correspondence:- Mohamed Abdelgawad Email: mohamedabdelwahab976@yahoo.com Tel:+966595435214

Accepted: 18 October 2018 Published: 30 November 2018

Citation: Alkhaldi AA, Abdelgawad MA. Synthesis, antimicrobial evaluation and docking studies of new pyrazolone derivatives. Trop J Pharm Res 2018; 17(11):2235-2241 doi: 10.4314/tjpr.v17i11.18

© 2018 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To synthesize new antimicrobial azo-pyrazolone derivatives III & IV and evaluate their antimicrobial activities using a combination of in vitro and molecular docking studies.

Methods: Azopyrazolone compounds were prepared from the reaction of substituted aniline diazonium with ethyl acetoacetate to give azoxobutyric acid derivatives (II) which were then reacted with phenyl hydrazine or hydrazine hydrate. The pyrazolone derivatives (IV) were acetylated with glacial acetic acid to yield new acetylated pyrazolones (V). An agar dilution method was used to demonstrate the antimicrobial activities of the pyrazolone derivatives and their minimum inhibitory concentration (MIC) values calculated. Molecular docking studies were employed to further evaluate the most active compounds (on the basis of the MICs obtained).

Results: The new pyrazolone derivatives showed varying antimicrobial activities (from negligible to strong) against a number of microorganisms. Derivatives IIIb and Vb showed potent activities against Bacillus subtilis, Sarcina lutea, Staphylococcus aureus and Enterococcus faecalis. However, the new compounds did not show antifungal activity. Molecular docking results for compounds IIIb and Vb were consistent with their antimicrobial activities and proved that the compounds inhibited glucosamine-6-phosphate synthase.

Conclusion: The new dichloropyrazolone compounds IIIa and Vb possess potent antimicrobial activities. These compounds have promising potential for use as new antibacterial agents or as templates for the design of new antimicrobial drugs.

Keywords: Azo-pyrazolone, Dichloropyrazolone, Antimicrobial, Molecular docking