Design, Synthesis, and Biological and In Silico Study of Fluorine‐Containing Quinoline Hybrid Thiosemicarbazide Analogues

• Published in: Journal of heterocyclic chemistry Vol. 56; no. 8; pp. 2235 - 2252
• Main Authors: Patel, Dhaval B., Patel, Kinjal D., Prajapati, Neelam P., Patel, Krupa R., Rajani, Dhanji P., Rajani, Smita D., Shah, Naumita S., Zala, Devendra D., Patel, Hitesh D.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.08.2019; Wiley Subscription Services, Inc
• Subjects: Ampicillin; Antibacterial materials; Biological activity; Chemistry; Chemistry, Organic; Cytotoxicity; E coli; Fluorine; Fungicides; Lymphocytes; Molecular docking; Molecular dynamics; Physical Sciences; Quinoline; Science & Technology; Synthesis; Thiosemicarbazides; Toxicity; Viability; VITRO; PHASE; ACID; PHARMACOPHORE PERCEPTION; ANTIMALARIAL ACTIVITY; INHIBITORS; MULTIDRUG-RESISTANCE; MOLECULAR DOCKING; DERIVATIVES
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.3617

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 compounds 8d and 8l [minimal inhibitory concentration (MIC) 62.5 μg/mL] were shown to have higher biological activity than ampicillin against Escherichia coli. Compound 8b (MIC 25 μg/mL) was shown to have the highest activity than was ampicillin against Staphylococcus aureus. The antifungal results demonstrated that compound 8j (MIC 100 μg/mL) has shown good activity. Most of the targeted compounds have shown potent antimalarial activity. Compounds 8d (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), and 8l (0.28 μg/mL) have notable activity than does the reference drug quinine. Compounds 8d (0.27 μg/mL), 8g (0.30 μg/mL), and 8k (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), and 8k (99.51)] at a maximum dose (10 μg/mL), depicting no cytotoxicity of these compounds on human lymphocytes in vitro. A molecular docking study was performed on Pf‐DHFR‐TS inhibitor. A molecular dynamics study has shown compound 8g to have better affinity with protein. ADME‐Tox and pharmacophore study of synthesized compounds suggested prediction of active site.