Synthesis, Docking, ADME‐Tox Study of 2‐(2‐(2‐Chlorophenyl)quinoline‐4‐carbonyl)‐N‐substituted hydrazinecarbothioamide Derivatives and Their Biological Evaluation

Abstract

A series of 2‐(2‐(2‐chlorophenyl)quinoline‐4‐carbonyl)‐N‐substituted hydrazinecarbothioamide derivatives were synthesized by facile and efficient conventional method. The structures of the compounds were elucidated with the aid of an elemental analysis, IR, ESI‐MS, 1H‐NMR, and 13C‐NMR spectral data. The synthesized compounds were evaluated for their in vitro antibacterial, antifungal, antimalarial, and antituberculosis activity against standard drugs. The bacterial studies were determined against gram‐positive and negative bacteria. These compounds were found to a broad spectrum of activity against the screened bacteria, but poor activity was observed against Pseudomonas aeruginosa and Escherichia coli. Compounds 8d, 8f, 8i, 8l, and 8n showed the potent activity against Staphylococcus aureus. Compounds 8d, 8g, 8k, 8l, and 8q show the potent activity against antimalarial as compared with the standard drugs Chloroquine, Quinine and compounds 8h, 8n, and 8o shows mild activity against H37Rv strain. Molecular docking revealed that synthesized derivatives and target proteins were actively involved in a binding pattern and had a significant corelation with biological activity. We have also performed a molecular dynamics and ADME‐Tox parameters for the synthesized compounds.

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

“…These compounds were subsequently treated with con. H 2 SO 4 with ethanol under reflux condition for the ethyl ester of compound; obtained products were directly used as starting materials to form hydrazide via ethanolic condensation reaction with hydrazine hydrate . Previously synthesized hydrazides and various isothiocyanates were added in the ethanol under reflux condition to afford final products in good yield (Scheme ) (Table , entries 1 to 12).…”

“…In continuation of our research, we have designed quinoline hybrid thiosemicarbazide analogues for their in vitro biological. Our previous work on quinoline hybrid thiosemicarbazide analogues demonstrated promising antimalarial analogues as compared with the standard chloroquine . In the present study, we have tried to develop new fluorinated analogues as potent molecules against diseases.…”

Quinoline: A Promising Scaffold in Recent Antiprotozoal Drug Discovery

“…The thiosemicarbazone-bridged 2-(2-chorophenyl) substituted quinoline derivatives have been engineered intended to check antimalarial properties. [2] Noteworthy-to-moderate P. falciparum inhibitory potencies (Minimum inhibition concentration, MIC = 0.11-1.78 μg/mL) are noticed for screened derivatives. In comparison with Chloroquine (MIC = 0.02 μg/ mL), no evaluated derivative has displayed decent activity.…”

“…Description of the structures of potent anti-antimalarial agents. [1][2][3][4] Figure 2. Depiction of haloquinoline derivatives as potent P. falciparum agents.…”