Flurbiprofen clubbed schiff's base derivatives as potent anticancer agents: In Vitro and In Silico approach towards breast cancer

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In this work, we are reporting nineteen hydrazone-Schiff base derivatives (2a-2l and 3a-3g), containing flurbiprofen drug nucleus. The synthesized products were structurally elucidated through 1H, 13C-NMR and HR-ESI-MS spectroscopic techniques and finally tested for in vitro anti-cancer activity. Among the synthetic series, 2f, 2g, 3g, 3b, and 2e attributed the higher inhibitory potential against the breast cancer cell line (MDA-MB-231) having IC50 values of 21.0 ± 0.4, 21.8 ± 0.2, 27.1 ± 0.3, 28.8 ± 0.3, and 29.6 ± 0.3 µM respectively. However, the remaining derivatives attributed good to less active. DFT was used to calculate frontier molecular orbital of (2a-h, j-l, and 3a-d) including HOMO which concentrated on the substituents aromatic ring, and LUMO focused over flurbiprofen and hydrazide fragments, that indicate the charge transfer from molecule to biological media. The reactivity indices suggested the most active 2f (IC50 = 21.0 ± 0.4 µM) and 2g (IC50 = 21.8 ± 0.2 µM) showed higher indices reactivity namely σ, χ, and ω than lowest active 2g; this relation inversely for Eg, η, and IP. 2a-l had more electrophilic character and higher acceptance ability for biological targets than compounds (3a-g). The MEP map indicated the electron density distribution of 2a-l was more dispersed than that of 3a-g, indicating potential biological activities and are chemically reactive zone suitable for drug action. The docking study contributed to the analysis of cytotoxicity for investigated compounds.