Ring opening ring closure reactions with 5,9-diethyl-7-(chromon-3-yl)-7-hydroquinolino[3′,4′:5,6]pyrano[3,2-c]quinoline-6,8(5H,9H)-dione with some 1,2-binucleophiles: Synthesis, characterization, DFT study and biological activity

Abstract

The chemical behaviour of electron deficient substrate 1 was investigated with some 1,2-bi-nucleophilic reagents. Reaction of substrate 1 with hydrazine derivatives namely hydrazine hydrate, phenylhydrazine, 7‑chloro-4-hydrazinoquinoline and 3-hydrazino-5,6-diphenyl-1,2,4-triazine led to 7-pyrazolylquinolinopyranoquinolines 2, 3, 6 and 7, respectively. These reactions proceed through γ-pyrone ring opening followed by pyrazole ring closure. Moreover, treating compound 1 with hydroxylamine hydrochloride provided 7-isoxazolylquinolino[3′,4′:5,6]pyrano[3,2-c]quinoline 8. The molecular structures were optimized utilizing DFT/B3LYP functional with 6–311G+(d,p) basis sets for all compounds. Moreover, global reactivity descriptors like chemical potential (μ), electronegativity (χ), hardness (η), softness (S) and electrophilicity index (ω) were computed to predict the chemical reactivity and kinetic stability of the synthesized compounds. The locations susceptible to attack by electrophiles and nucleophiles were examined at the same theoretical level by using molecular electrostatic potential (MEP) and condensed Fukui functions. The NMR chemical shifts were computed by the Gauge Independent Atomic Orbital (GIAO) method and compared to the experimental results. The first hyperpolarizability of the prepared compounds is higher than urea, so serves as good candidate for nonlinear optical (NLO) materials. The synthesized substances were tested for their efficacy as antimicrobial agents against a variety of bacterial and fungal species. Additionally, the present compounds revealed some antitumor activity (compounds 3 and 7 showed activity comparable to cis-platin, used as a reference drug in the assay). Furthermore, the synthesized compounds were moderately compliant with Lipinski's rule of five, suggesting that related compounds might be suitable for oral administration as medications.