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, H-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 IC values 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.

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

“…In vitro cytotoxic activity of prepared compounds was assayed using MTT assay in which the formation of formazan during the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide in the mitochondria of live cells in response to the succinate dehydrogenase enzyme is measured ( 25 ). The amount of produced formazan is related to the number of viable cells.…”

Synthesis and Anti‐Fungal/Oomycete Activity of Novel Sulfonamide Derivatives Containing Camphor Scaffold

“…The crystallographic pattern of SDH (PDB codes: 2FBW) was obtained from Protein Data Bank. The energy‐minimizing the structures of 2d and carboxin and procedure of molecular docking were both carried out via Discovery Studio 2016 program [31,39,40] . The previous ligand was extracted, and all water molecules were eliminated from the crystal complex.…”

Synthesis and Characterization of Chalcone‐Pyridinium Hybrids as Potential Anti‐Cancer and Anti‐Microbial Agents

“…Besides, the existing anticancer drugs search for the new, potential and selective drugs with new mechanism of action to treat the cancer remains a major concern in the cancer research. Molecular hybridization allowing us to design such hybrids with target of interest and versatile biological potential in which two or more biologically potent heterocyclic pharmacophores embedded in it . The molecules incorporating chalcone with variety of heterocyclic moieties viz., indole, triazole, thiazole, quinoline, quinoxaline, piperzine etc.…”