Multi-targeted molecular docking, drug-likeness and ADMET studies of derivatives of few quinoline- and acridine-based FDA-approved drugs for anti-breast cancer activity

• Published in: Structural chemistry 2022-06, Vol.33 (3), p.649-669
• Main Authors: Sing, Lai Cong, Roy, Anitha, Hui, Lok Yong, Mun, Chan Sook, Rajak, Harish, Karunakaran, Rohini, Ravichandran, Veerasamy
• Format: Article
• Language: English
• Subjects: Affinity; Binding; Breast cancer; Cancer; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Development and progression; Drug approval; Drug therapy; Drugs; Enzymes; Epidermal growth factor; Growth factors; In vivo methods and tests; Molecular docking; Molecular interactions; Original Research; Physical Chemistry; Prevention; Quinoline; Receptors; Sparfloxacin; Theoretical and Computational Chemistry
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-022-01878-3

Quinoline- and acridine-based drugs are widely used as anti-breast cancer agents. These drugs act through various mechanisms of action; for example, neratinib acts on epidermal growth factor receptor 1 (EGFR) and human epidermal receptor type 2 (HER2) enzymes, whereas amsacrine and pyrazoloacridine act on topoisomerase II enzymes. The objective of the present study was to explore and compare the interaction mechanism of knowledge-based designed derivatives of FDA-approved quinoline- and acridine-based drugs. The above-stated cancer proteins were collected from PDB, prepared by correcting any broken chains, removing water and adding charges. Docking studies were performed in the PyRx docking tool, and Discovery Studio Visualizer was used to visualize the molecular interactions. The result obtained found that neratinib had a better binding affinity towards EGFR and HER2 but weaker binding affinity towards topoisomerase IIα and topoisomerase IIβ. On the other hand, amsacrine and pyrazoloacridine were found to have better binding scores in topoisomerase IIα and topoisomerase IIβ instead of EGFR and HER2, as already proved experimentally. All the designed molecules have shown better binding affinity to their favourable enzymes and other enzymes involved in breast cancer development. The outcome reveals that the designed quinoline- and acridine-based drugs derivatives could be examined as a potent inhibitory drug of breast cancer for their strong multi-targeted inhibition ability and reactivity. Further synthesis, in vitro and in vivo investigations of designed derivatives may be done to prove their therapeutic potential in breast cancer treatment.