Design, Synthesis, and Biological andIn SilicoStudy of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

A novel series of fluorine‐containing quinoline hybrid thiosemicarbazide analogues (8a–8l) were synthesized and tested for their biological activities. The antibacterial results demonstrated that compounds8dand8l[minimal inhibitory concentration (MIC) 62.5 μg/mL] were shown to have higher biological activity than ampicillin againstEscherichia coli. Compound8b(MIC 25 μg/mL) was shown to have the highest activity than was ampicillin againstStaphylococcus aureus. The antifungal results demonstrated that compound8j(MIC 100 μg/mL) has shown good activity. Most of the targeted compounds have shown potent antimalarial activity. Compounds8d(0.19 μg/mL),8g(0.30 μg/mL),8h(0.36 μg/mL),8k(0.10 μg/mL),8l(0.28 μg/mL),8k(0.10 μg/mL), and8l(0.28 μg/mL) have notable activity than does the reference drug quinine. Compounds8d(0.27 μg/mL),8g(0.30 μg/mL), and8k(0.17 μg/mL) have shown excellent activity against chloroquine‐resistant strain. The MTT assay performed on peripheral blood lymphocyte cultures showed a high percentage of lymphocyte viability [8d(99.64),8g(99.46),8h(98.83), and8k(99.51)] at a maximum dose (10 μg/mL), depicting no cytotoxicity of these compounds on human lymphocytesin vitro. A molecular docking study was performed onPf‐DHFR‐TSinhibitor. A molecular dynamics study has shown compound8gto have better affinity with protein. ADME‐Tox and pharmacophore study of synthesized compounds suggested prediction of active site.