title: Synthesis, in Vitro and in Silico Studies of Some Novel 5-Nitrofuran-2-yl Hydrazones as Antimicrobial and Antitubercular Agents.
abstract: In this study, we synthesized two series of novel 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e in addition to a third series of thiophene-2-carbohydrazides 23a-g to develop potent antimicrobial and/or antitubercular agents. The newly synthesized compounds were evaluated in vitro for their antimicrobial and antimycobacterial activities. Most of the 5-nitrofuran-2-carbohydrazides 21a-h and 22a-e displayed variable activity against Aspergillus fumigates, Staphylococcus aureus, Streptococcus pneumonia, Bacillis subtilis, Salmonella typhimurium, Klebsiella pneumonia, Escherichia coli and Mycobacterium tuberculosis. The sulfonamide derivative 21f exhibited superior potency and broad-spectrum antimicrobial activity with minimum inhibitory concentration (MIC)=0.06-0.98 µg/mL and antimycobacterial activity with MIC=3.9 µg/mL. The 5-nitrofuran-2-carbohydrazides 21a, b, g, h and 22a-c exhibited significant antibacterial activity with MIC values in the range of 0.12-7.81 µg/mL. The significances of the 5-nitrofuran moiety and sulfonamide function were explored via the structure-activity relationship (SAR) study. In addition, docking studies revealed that the p-amino benzoic acid (PABA) and binding pockets of the dihydropteroate synthase (DHPS) were successfully occupied by compound 21f. Furthermore, two quantitative structure-activity relationship (QSAR) models were built to explore the structural requirements which controlled the activity.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University.
authors.forename: Hatem Abdel-Kader
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.forename: Wagdy Mohamed
authors.initials: WM
authors.lastname: Eldehna
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fares
authors.forename: Tilal
authors.initials: T
authors.lastname: Elsaman
authors.forename: Marwa Mostafa
authors.initials: MM
authors.lastname: Abdel-Aziz
authors.forename: Dalia Hussein
authors.initials: DH
authors.lastname: Soliman
mesh_terms: D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D004094:Dihydropteroate Synthase / Q000378:metabolism; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D006835:Hydrazones; D004094:Dihydropteroate Synthase; D010129:4-Aminobenzoic Acid