Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents

• Published in: Bioorganic chemistry 2021-11, Vol.116, p.105381-105381, Article 105381
• Main Authors: Kavalapure, Rohini S., Alegaon, Shankar G., Venkatasubramanian, U., Priya, A. Soundarya, Ranade, Shriram D., Khanal, Pukar, Mishra, Sanjay, Patil, Dhanashree, Salve, Preeti S., Jalalpure, Sunil S.
• Format: Article
• Language: English
• Subjects: 7-Chloro-N-phenylquinolin-4-amine; Animals; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biphenyl Compounds - antagonists & inhibitors; Cell Line; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Design; Drug-likeness; Eg5 inhibitor; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Kinesins - antagonists & inhibitors; Kinesins - metabolism; Mice; Molecular docking; Molecular Docking Simulation; Molecular Structure; Picrates - antagonists & inhibitors; Qikprop; Schiff base; Schiff Bases - chemical synthesis; Schiff Bases - chemistry; Schiff Bases - pharmacology; Structure-Activity Relationship
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105381

[Display omitted] •Synthesis of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base heterocyclic compounds.•Out of eighteen compounds, seven compounds exhibited promising Eg5 inhibitory activity.•In vitro evaluation of the antioxidant (DPPH) assay and cytotoxicity (MTT) activities.•Molecular docking studies were carried out using Glide software.•ADME and Drug-likeness parameters are predicted using Qikprop software. In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.