Synthesis, structural properties and potent bioactivities supported by molecular docking and DFT studies of new hydrazones derived from 5-chloroisatin and 2-thiophenecarboxaldehyde

•Synthesis of N-alkylated 5-chlorosatin based hadrazones and their characterization•In vitro antioxidant potential and enzyme inhibition was tested•Molecular Docking studies supported the enzyme inhibition results.•DFT studies were executed to investigate the supramolecular assemblies and noncovalent interactions. New hydrazones were synthesized by employing a convergent synthetic methodology involving condensation of N-alkyl 5-chloroisatins with hydrazone derived from 2-thiophenecarboxaldehyde. The synthesized compounds were fully characterized using UV/Vis., Infrared, 1H and 13C NMR spectroscopies as well as single crystal X-rays diffraction analysis. Bader's theory of ‘atoms in molecules’ confirmed the existence of all nonbonding interactions. Connectivity between isomers of synthesized compounds was characterized by the distribution of critical points, isatin surfaces, and bond paths. The presence of electrostatic potential on oxygen and hydrogen atoms was evaluated by means of MEP calculations, which showed that the oxygen atom acts as nucleophilic center for electrophilic hydrogen atom. Compound 6 exhibited potent anti-oxidant potential (DPPH, ABTS, NBT) with IC50 values of 46 ± 0.72 μM/mL. These compounds were also screened for in vitro cholinesterases inhibition, where compound 6 presented effective inhibition against AChE and BChE in comparison to the standard drugs; allanzanthane and galanthamine in a dose reliant mode. The IC50 values of both compounds (6 and 7) against AChE were determined to be 20.21 ± 0.06 & 16.22 ± 0.18 μM and against BChE, as 28.01 ± 0.01 & 20.11 ± 0.12 μM, respectively. Molecular docking studies supported these results and helped to establish structure activity relationship. The results reported in this manuscript are anticipated to be beneficial for understanding the solid-state architecture of the X-ray structures of new hydrazone conjugates of 5-chloroisatin & 2-thiophenecarboxaldehyde. On the other hand their intriguing biological potentials can create quest among scientific community to further analyze such molecules for drug discovery purposes. [Display omitted]