Yoga Priastomo, Anggit Fitria, Tutik Dwi Wahyuningsih, Deni Pranowo, Artania Adnin Tri Suma, Ninik Andriyani, Syaiful Muhklis
A crucial aspect of the antibacterial activity of N-phenyl pyrazolines is the presence of specific substituents in their structures. Besides, several important elements require further investigation. In this study, we synthesized a series of N-phenyl pyrazoline derivatives bearing electron-donating group substituents derived from vanillin and electron-withdrawing groups obtained from halogens. These compounds were evaluated against both Gram-positive and Gram-negative bacteria using in vitro and computational studies. The in vitro study revealed that N-phenyl pyrazoline containing the electron-donating groups (hydroxy [–OH] and methoxy [–OCH3]) exhibited strong antibacterial activity against Gram-negative bacteria, including Escherichia coli and Shigella flexneri, as well as moderate activity against Gram-positive bacteria, such as Staphylococcus aureus and Bacillus subtilis. Furthermore, the results of the computational study supported these findings. It demonstrated that the electron-donating groups (–OH and –OCH3) were capable of forming molecular interactions similar to those of tetracycline with several key amino acids in the DNA gyrase (GyrB receptor), including Glu50, Asp73, and Arg76, which are essential for bacterial survival. However, the presence of the electron-withdrawing groups (bromo [–Br] and chloro [–Cl]), in conjunction with the electron-donating groups, decreased antibacterial activity against all tested bacteria, resulting in moderate to weak activity. © 2025 Wiley-VCH GmbH.
Department of Chemistry Education, Faculty of Mathematics and Natural Sciences, Universitas Negeri Yogyakarta, D.I. Yogyakarta, Depok, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Gadjah Mada, Sekip Utara, D.I. Yogyakarta, Bulaksumur, Indonesia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Bulaksumur, Yogyakarta, Indonesia
