title: Biologically Active Heterocyclic Hybrids Based on Quinazolinone, Benzofuran and Imidazolium Moieties: Synthesis, Characterization, Cytotoxic and Antibacterial Evaluation.
abstract: Cytotoxic and antimicrobial agents structurally based on quinazolinone, benzofuran and imidazole pharmacophores, have been designed and synthesized. Spectral (IR,1H-NMR) and elemental analysis data established the structures of these novel 3-[1-(1-benzofuran-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)ethyl]-1-methyl-1H-imidazol-3-ium chloride hybrid derivatives. All the synthesized compounds were evaluated for in vitro cytotoxicity and antimicrobial activities. Cytotoxic evaluation using MTT assay revealed that compounds 12c, 12g and 12i exhibited significant cytotoxicity with IC50values 1, 1, and 0.57 μm on this cell line, respectively. Biological activity of the synthesized compounds as antibacterial agent were also evaluated against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungi (Candida albicans) strains. All compounds 12a - 12i showed slightly higher activity against Gram-positive bacteria than the Gram-negative one. Among the nine new compounds screened, 3-[1-(5-bromo-1-benzofuran-2-yl)-2-(6-chloro-4-oxoquinazolin-3(4H)-yl)ethyl]-1-methyl-1H-imidazol-3-ium chloride (12e) has pronounced higher antimicrobial activity against all tested strains. These results demonstrated potential importance of molecular hybridization in the development of new lead molecules with major cytotoxicity and antimicrobial activity.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Asadi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.
authors.forename: Ghadamali
authors.initials: G
authors.lastname: Khodarahmi
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanian-Najafabadi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.
authors.forename: Lotfollah
authors.initials: L
authors.lastname: Saghaie
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Hassanzadeh
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry; D002176:Candida albicans / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D061986:MCF-7 Cells; D052999:Quinazolinones / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001572:Benzofurans; D006571:Heterocyclic Compounds; D007093:Imidazoles; D052999:Quinazolinones
keywords: Antibacterial activities; Benzofuran; Cytotoxic activities; Imidazolium salt; Quinazolinone