Abstract
Acid catalyzed condensation of isoniazid with a number of suitably substituted aromatic and heterocyclic aldehydes was carried out in dry ethanol to afford the title (E)-N′-(substituted benzylidene/methylene) isonicotinohydrazides (SF 1 – SF 4) in good yields. These compounds were characterized and further investigated for their binding with ds.DNA using UV– spectroscopy and molecular docking and for antitumor and antimicrobial potentials. A good correlation was found among spectroscopic, theoretical and biological results. UV– spectra in the presence of DNA concentrations and their data interpretation in terms binding constant “Kb” and free energy change (ΔG) provided evidences for the significant and spontaneous binding of the compounds with DNA. Molecular docking studies and structural analysis further supported the UV-findings and indicated that the modes of interactions between bromo- (SF 1) and flouro- (SF 4) substituted isonicotinohydrazides is intercalation while methoxy- (SF 2) and hydroxy- (SF 3) substituted isonicotinohydrazides interact with DNA helix via groove binding. SF 1 exhibited comparatively higher Kb value (UV–; 8.07 × 103 M−1, docking; 8.11 × 103 M−1) which inferred that the respective compound muddles to DNA most powerfully. SF 1 has shown the lowest IC50 (345.3 μg/mL) value among all the compounds indicating its comparatively highest activity towards tumor inhibition. None of the compound has shown perceptible antibacterial and antifungal activities.
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•Bromo- (SF 1) and flouro- (SF 4) substituted isonicotinohydrazides intercalate within DNA base pairs.•Methoxy-(SF 2) and hydroxy-(SF 3) substituted isonicotinohydrazides interact with DNA helix via groove binding.•Greater Kb inferred that SF 1 muddles to DNA most powerfully.•Lowest IC50 value showed better tumor inhibition activity of SF 1.•Good correlations among spectroscopic, docking and biological findings.