A1 Journal article (refereed)
Prodrugs of sulfacetamide : Synthesis, X-ray structure, Hirshfeld analysis, antibacterial assessment, and docking studies (2022)

Ayoup, M. S., Soliman, S. M., Haukka, M., Harras, M. F., Menofy, N. G., & Ismail, M. M. (2022). Prodrugs of sulfacetamide : Synthesis, X-ray structure, Hirshfeld analysis, antibacterial assessment, and docking studies. Journal of Molecular Structure, 1251, Article 132017. https://doi.org/10.1016/j.molstruc.2021.132017

JYU authors or editors

Publication details

All authors or editors: Ayoup, Mohammed Salah; Soliman, Saied M.; Haukka, Matti; Harras, Marwa F; Menofy, Nagwan G.El.; Ismail, Magda M.F.

Journal or series: Journal of Molecular Structure

ISSN: 0022-2860

eISSN: 1872-8014

Publication year: 2022

Volume: 1251

Article number: 132017

Publisher: Elsevier

Publication country: Netherlands

Publication language: English

DOI: https://doi.org/10.1016/j.molstruc.2021.132017

Publication open access: Not open

Publication channel open access:

Abstract

New prodrugs of sulfacetamide as azo compounds were synthesized and have been evidenced through elemental and spectral analyses. Their synthesis were carried out by coupling the diazonium salt of sulfacetamide with activated carbanion salt of ethyl acetoacetate at 0 °C to afford the hydrazono derivative 3. Other prodrugs as sulfacetamide-pyrazoles, 5a, 5b and 5c were furnished via cyclocondensation of 3 with aryl/heteroaryl hydrazines. X-ray diffraction for single crystal was used to confirm the molecular and supramolecular structures of 3. In addition, DFT studies were performed to analyze the geometric parameters and compute the electronic properties of 3 and 5a-c. Hirshfeld analysis revealed the importance of the H…H, O…H and H…C intermolecular contacts in the molecular packing of 3. Moreover, all prodrugs were docked in the active site of the target enzyme (DHPS) exhibiting good affinity except 5c. In addition, the minimum inhibitory concentration test showed that, compounds 3, 5a, and 5b are broad-spectrum antibacterial possessing 2 folds the activity of the reference standard, sulfamethoxazole against clinical isolates of E. coli, K. pneumonia and P. aeruginosa.. The prodrug 5a showed better DHPS inhibition than that of sulfadiazine.

Keywords: organic compounds; sulphur compounds; prodrugs; antimicrobial compounds; chemical synthesis; computational chemistry

Free keywords: Sulfacetamide; Prodrug; Computational studies; Docking; Antibacterial; DHPS inhibitors; Hirshfeld

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2022

JUFO rating: 1