Synthesis, Molecular Docking Study, and Biological Evaluation of New 4-(2,5-Dimethyl-1<i>H</i>-pyrrol-1-yl)-<i>N</i>’-(2-(substituted)acetyl)benzohydrazides as Dual Enoyl ACP Reductase and DHFR Enzyme Inhibitors
Mater H. Mahnashi,
Pooja Koganole,
Prem Kumar S. R.,
Sami S. Ashgar,
Ibrahim Ahmed Shaikh,
Shrinivas D. Joshi,
Ali S. Alqahtani
Affiliations
Mater H. Mahnashi
Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia
Pooja Koganole
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, Karnataka 580002, India
Prem Kumar S. R.
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, Karnataka 580002, India
Sami S. Ashgar
Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Ibrahim Ahmed Shaikh
Department of Pharmacology, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia
Shrinivas D. Joshi
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, Karnataka 580002, India
Ali S. Alqahtani
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha 62529, Saudi Arabia
In this study, a new series of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N’-(2-(substituted)acetyl) benzohydrazides (5a–n) were prepared and new heterocycles underwent thorough characterization and evaluation for antibacterial activity; some of them underwent further testing for in vitro inhibition of enoyl ACP reductase and DHFR enzymes. The majority of the synthesized molecules exhibited appreciable action against DHFR and enoyl ACP reductase enzymes. Some of the synthesized compounds also showed strong antibacterial and antitubercular properties. In order to determine the potential mode of action of the synthesized compounds, a molecular docking investigation was conducted. The results revealed binding interactions with both the dihydrofolate reductase and enoyl ACP reductase active sites. These molecules represent excellent future therapeutic possibilities with potential uses in the biological and medical sciences due to the compounds’ pronounced docking properties and biological activity.
