Design, Synthesis, Antimicrobial Activity, and Molecular Docking of Some New Diclofenac Derivatives

Abstract

Due to the biological importance of diclofenac derivatives which are included in the composition of the active substance in many medicines used in the treatment of infections. Herein, we present a facile procedure for the synthesis of a new series of diclofenac analogous, in excellent isolated yields starting from the carbohydrazide precursor 1. Acylation and condensation of NH₂ group in the starting material with different reagents delivered compounds (2–5). Moreover, the Nucleophilic substitution of chloromethyl derivative 5 with primary and secondary amines gave compounds (6a, 6b, and 7). Furthermore, the hydrazine compound (7) reaction with benzaldehyde and chloroacetylchloride produced derivatives (8, 9). The chemical structures of all newly synthesized compounds have been proved based on elemental and spectral analysis techniques (FTIR, ¹HNMR, ¹³CNMR, and Mass spectroscopy). All synthesized compounds were investigated for their in-vitro antimicrobial activity against different strains of bacteria and fungi in moderate to high activity. A molecular docking approach was utilized to investigate the proposed molecular mechanism of the antibacterial and antifungal activity of the synthesized compounds.

Keywords:

• Diclofenac
• synthesis
• antibacterial activity
• antifungal activity
• molecular docking

Acknowledgments

The authors are very grateful to Dr. Youssif Shaban and Dr. Hossam Rafaat from Upper Egypt Pharmaceuticals Company – UP Pharma) for providing us with the starting material and analysis. We would like also to thank Prof. Mostafa Ahmed from New Valley University for his continuous encouragement.

Disclosure statement

The authors declared no conflict of interest, including any financial, personal, or other ties with other persons or enterprises.