In-Silico exploration: Unraveling the anti-cancer potential of 8-Nitroquinoline hydrazides

Abstract

The proliferation of cancer has propelled the scientific community to expedite drug discovery to nullify the threats of cancers on health segment. Addressing the adverse impact of cancer on health necessitates the effective solution. The profound activity of quinoline core appended heterocyclic derivatives against cancer proliferation impacts their significance in cancer pathology. The hydrazides of 8-nitroquinoline derivatives were synthesised, and their structures were characterized through IR, NMR and single crystal XRD techniques. Initially, the theoretical calculations like green chemistry metrics and DFT studies of the 6a-c have successfully elucidated through FMO, molecular reactivity descriptors, MEP mapping approaches. Outcomes of the studies clearly indicate that the synthesised quinoline hydrazides were highly capable to interact with the biological target entities. In-Silico studies explicit the role of organic small molecules and its efficiency to be the potent drug candidates in therapeutics. Computationally the ADMET studies and the molecular docking performance of 6a-c demonstrated to expose the pharmacokinetic behaviour and binding probability assessments with 11 different oncogenic receptors. The compound 6c could be found as favourable drug molecule adhered from its drug likeness, which comply with most of the ADMET properties. Moreover notably, methyl substituted 6c exhibits its potential binding efficiency with CDK2 and PI3K macromolecules bearing -8.7 & -7.5 kcal/mol binding affinity over 6a & 6b among the selected oncogenic proteins. The insights of in-silico studies could be validated further through in-vitro and in-vivo wet lab research works.