Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives.

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1-24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204-0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

Antimicrobial Activity of New 2-Thioxo-benzo[g]quinazolin-4(3H)-one Derivatives.

BACKGROUND: The antimicrobial activity of a synthesized series of 28 2-thioxobenzo[ g]quinazolin-4(3H)-one derivatives was evaluated in vitro against five Gram-positive bacteria, including Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The antibacterial activity was extended to include five Gramnegative bacteria: Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Enterobacter cloacae. Furthermore, the antifungal activity was evaluated against 10 fungal strains, including Aspergillus fumigatus, Syncephalastrum racemosum, Geotricum candidum, Candida albicans, Aspergillus niger, Cryptococcus neoformans, Candida tropicalis, Penicillium expansum, Microsporum canis and Trichophyton mentagrophytes. METHODS: The agar well diffusion method was adopted against Gram-positive and Gram-negative bacteria and fungi, using ampicillin, gentamicin and amphotericin B as reference drugs, respectively. RESULTS: The findings of the antibacterial studies revealed that most of the tested compounds possess strong activity against both bacterial species. Compounds 8 and 23 were the most active on Grampositive bacteria, while several compounds demonstrated significant antibacterial activity on Gramnegative bacteria, especially Escherichia coli. Furthermore, several compounds showed strong antifungal activity against many of the investigated fungi. The obtained results were reinforced by determination of the minimum inhibitory concentration for the active compounds against Grampositive and Gram-negative bacteria, as well as fungi, compared to the reference drugs. CONCLUSION: Many of the investigated compounds showed potent activity against all tested microbial species. The discovery has provided a foundation for the synthesized compounds to serve as a platform for further design and development of more potent antimicrobial agents.