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

Abstract

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.

Quinoline: A Promising Scaffold in Recent Antiprotozoal Drug Discovery

“…The antimalarial property with respect to P. falciparum of thiosemicarbazone derivatives has been determined; wherein thiosemicarbazone functionality is flanked by alkyl/aryl substituent on one side and haloquinoline moiety on other side [7] . In this activity, a decent antimalarial profile is noticed for the tested molecules.…”

“…Depiction of haloquinoline derivatives as potent P. falciparum agents. [5][6][7] fluoroquinoline 2-position and a 4-nitrophenyl moiety at thiosemicarbazone end has elicited eminent potency (MIC = 0.10 μg/mL). However, small decrement in inhibitory activity (MIC = 0.17 μg/mL) is seen in the case of 7-chloro-6-fluoroquinoline 19 with 3,5-dichlorophenyl ring at thiosemicarbazone end revealing the importance of 4-nitrophenyl moiety.…”

Recent update on antibacterial and antifungal activity of quinoline scaffolds

“…Fluoroquinoline moiety is connected to the substituted phenyl ring at quinoline 2‐position in addition to the substituted phenyl moiety at quinoline 4‐position via thiosemicarbazone fragment in the fluorine‐containing quinoline hybrid thiosemicarbazide series. [ 32 ] In this regard, compound 34 (Figure 7) entailing 8‐trifluoroquinoline bicycle, wherein 2‐chlorophenyl ring is attached at 2‐position alongside 2,6‐difluorophenyl moiety via thiosemicarbazone linker at 4‐position exhibited the strongest S. aureus inhibitory property (MIC = 25 µg/ml), followed by 3,5‐dichlorophenyl analog 35 (MIC = 62.5 µg/ml). Furthermore, the presence of 2,6‐difluorophenyl motif at quinoline 2‐position and simple phenyl ring connected with thiosemicarbazone fragment (compound 36 ) has resulted in E. coli and S. pyogenes dual antibacterial activity with MIC values of 62.5 and 50 µg/ml, respectively.…”

“…The antifungal properties of thiosemicarbazide analogs of quinoline are reported to be efficient in the case of C. albicans , wherein the inhibitory potency (MIC = 100 µg/ml) of compound 113 (Figure 17) is as good as nystatin. [ 32 ] Unlike the antibacterial counterpart, the moderate antifungal property is obtained with 4‐methylphenyl thiosemicarbazide motif. However, moderate‐to‐poor inhibitory potencies have been noticed for screened molecules against the fungal strains A. niger and A. clavatus .…”

Microwave assisted synthesis, biological activities, and in silico investigation of some benzimidazole derivatives

“…The regular dynamics on dissimilar timescales of a docked complex of derivatives 7s and protein (PDB: 5ZNI ) and molecular properties of the complex are conceded with the help of molecular dynamics (MD) stimulation. MD simulations have been accompanied by Desmond program [ 70 ] as implemented Schrödinger Materials Science Suite 2015‐4. [ 69 ] OPLS_2005 force field with NPT ensemble class have been utilized, while pressure and temperature were set to 1.0325 bar and 300 K, respectively.…”