Synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents.
New benzimidazole derivatives were synthesized and assessed for antimicrobial efficacy toward Escherichia coli, Bacillus cereus, Staphylococcus aureus, Candida albicans and Aspergillus fumigatus 293. Results indicated that compounds 3c and 3n have promising activity toward S. aureus, whereas 3i exhibited remarkable efficacy toward B. cereus. Moreover, compound 3c was proved to be the most active antifungal analog toward C. albicans. On the other hand, 3n displayed the highest activity against A. fumigatus 293. Antiquorum-sensing activity of the same compounds was also tested against Chromobacterium violacium ATCC 12472, whereas compounds 3c-f, 3i-k and 3m-o showed acceptable activity. In vitro antitumor testing of these compounds toward liver cancer (HepG2), colon cancer (HCT-116) and breast cancer (MCF-7) cell lines revealed that compound 3p has the highest potency against the three tested cell lines. Moreover, 3f, 3m and 3n displayed promising activity toward all tested cell lines. Compounds 3f, 3m, 3n and 3p were esteemed for in vivo antitumor activity against EAC cells. The active antimicrobial and antitumor analogs, 3a, 3c, 3f, 3i-k, 3m, 3n and 3p were assessed for DNA-binding affinity, and results indicated that 3c, 3f, 3i, 3k and 3n have strong DNA-binding affinity. The computational studies affirmed that almost all of the inspected compounds meet the optimal requirements for good absorption and oral bioavailability.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr.nadiaelgohary@yahoo.com.
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El-Gohary
Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Microbiology, College of Pharmacy, Taibah University, Almadinah Almunawwarah 344, Saudi Arabia.
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Shaaban
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001562:Benzimidazoles
Antimicrobial screening; Antiquorum-sensing screening; Antitumor screening; Benzimidazoles; Computational studies; Cytotoxicity testing; DNA-Binding assay; Synthesis