title: Antimicrobial and antiquorum-sensing studies. Part 3: Synthesis and biological evaluation of new series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles.
abstract: New series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles were synthesized. The newly synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Compounds 3b and 10a displayed the highest activity against E. coli with MIC value of 78.125 μg/mL. In addition, compound 10a exhibited the highest activity against B. cereus with MIC value of 156.25 μg/mL. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus flavus 3375. Compounds 3b, 5a, 10a, and 12b showed the best activity against A. flavus 3375 with MIC value of 19.531 μg/mL. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds 3b, 5a, and 12b exhibited moderate activity. In vitro cytotoxicity testing of compounds 3b,c, 5a, 6a, 10a, and 12a,b against human normal lung fibroblast (W138) cell line was performed. The in vivo acute toxicity of the same compounds was also tested and the obtained results indicated that compound 10a is the least toxic analog. The same compounds were studied for their DNA-binding affinity and the obtained results showed that compounds 3b, 10a, and 12a,b have moderate DNA-binding affinity.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Nadia S
authors.initials: NS
authors.lastname: El-Gohary
authors.forename: Mona I
authors.initials: MI
authors.lastname: Shaaban
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole
keywords: Antimicrobial activity; Antiquorum-sensing activity; Cytotoxic activity; Fused [1,3,4]thiadiazoles; In silico studies; In vivo acute toxicity; [1,3,4]Thiadiazoles