Synthetic Transformation of 2-{2-Fluoro[1,1'-biphenyl]-4-yl} Propanoic Acid into Hydrazide-Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study

Sajjad Ahmad; Momin Khan; Muhammad Ishaq Ali Shah; Mahboob Ali; Aftab Alam; Muhammad Riaz; Khalid Mohammed Khan

doi:10.1021/acsomega.2c05498

Synthetic Transformation of 2-{2-Fluoro[1,1'-biphenyl]-4-yl} Propanoic Acid into Hydrazide-Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study

ACS Omega. 2022 Nov 30;7(49):45077-45087. doi: 10.1021/acsomega.2c05498. eCollection 2022 Dec 13.

Authors

Sajjad Ahmad¹, Momin Khan¹, Muhammad Ishaq Ali Shah¹, Mahboob Ali², Aftab Alam³, Muhammad Riaz⁴, Khalid Mohammed Khan⁵

Affiliations

¹ Department of Chemistry, Abdul Wali Khan University, Mardan23200, Pakistan.
² Department of Chemistry, Government Degree college, Takht Bhai, Mardan23200, Pakistan.
³ Department of Chemistry, University of Malakand, Chakdara, Lower Dir18800, Pakistan.
⁴ Department of Chemistry, Government Degree college Garhi Kapura, Mardan23200, Pakistan.
⁵ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi75270, Pakistan.

Abstract

In the present study, 28 acyl hydrazones (4-31) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like ¹H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC₅₀ = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC₅₀ = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.