title: Synthesis, Antimicrobial, Antiquorum-Sensing, and Cytotoxic Activities of New Series of Isoindoline-1,3-dione, Pyrazolo[5,1-a]isoindole, and Pyridine Derivatives.
abstract: New series of isoindoline-1,3-diones 2-9, pyrazolo[5,1-a]isoindoles 10-14, and pyridines 16-18 were synthesized. Twenty of the synthesized compounds were screened for their antibacterial activity against S. aureus, B. cereus, and E. coli. Compound 5 was proved to be the most active member in this study, showing the highest antibacterial activity against the three selected microorganisms. The antifungal activity of these compounds was also tested against C. albicans and A. flavus 3375. Compounds 4, 5, 8, and 17a exhibited the best antifungal activity against A. flavus 3375. The same compounds were examined for their antiquorum-sensing activity against Ch. violacium ATCC 12472, whereas compound 5 displayed strong antiquorum-sensing activity. The in vitro cytotoxicity testing of compounds 4-9 and 17a against human normal lung fibroblast (W138) cell line revealed that compounds 4, 5, and 8 are the least cytotoxic analogs in this study. In vivo acute toxicity testing of compounds 4, 5, and 8 was performed. The DNA-binding affinity of compounds 4-9 and 17a was also tested and the obtained results showed that all tested compounds 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.affiliation: Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.|Department of Microbiology, College of Pharmacy, Taibah University, Almadinah Almunawwarah, Saudi Arabia.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Shaaban
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D054833:Isoindoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D054833:Isoindoles; D011720:Pyrazoles; D011725:Pyridines; D004247:DNA
keywords: Antimicrobial activity; Cytotoxic activity; In silico studies; In vivo acute toxicity; Isoindoline-1,3-diones; Pyrazolo[5,1-a]isoindoles; Pyridines