Novel thioether linked 4-hydroxycoumarin derivatives: Synthesis, characterization, in vitro pharmacological investigation and molecular docking studies

• Published in: Journal of molecular structure 2022-02, Vol.1249, p.131642, Article 131642
• Main Authors: Manjunatha, B., Bodke, Yadav D., Kumaraswamy, H.M., Meghana, P., Nagaraja, O., Anjan kumar, G.C.
• Format: Article
• Language: English
• Subjects: 4-hydroxycoumarin; Anti-inflammatory activity; Cytotoxic activity; HIF-1 alpha (3KCY); Mercaptotetrazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131642

•Novel thioether linked 4‑hydroxy coumarin derivatives were synthesised and characterized by spectroscopic techniques..•All the synthesised derivatives obeys the Lipinski rule of five, except 4f which has log p > 5.•Cytotoxic activity against HepG2 and MIAPaCa-2 cells: compound 4a displayed a significant activity.•Antioxidant and anti-inflammatory activity efficacy; compounds 4c and 4f exhibhited potent activity respectively.•In silico study with HIF-1 alpha (3KCY). In this paper, we reported the synthesis of a series of novel 4‑hydroxy-3-{phenyl [(1-phenyl-1H-tetrazol-5-yl) sulfanyl] methyl}-2H-chromen-2-one derivatives 4(a–f) using L-Proline as an organocatalyst under ambient temperature. The structure of the synthesized coumarin-tetrazole derivatives was precisely authenticated by IR, 1H NMR, 13C NMR and mass spectroscopic techniques. From the molecular properties calculation, it was confirmed that all the synthesized derivatives 4(a–f) except 4f obey the Lipinski rule which scrutinizes and hardened us to screen the coumarin derivatives for biological activities. The fetched derivatives 4(a–f) were screened for antioxidant, cytotoxic and anti-inflammatory activities.The compound 4f exhibhited potent antioxidant activity with IC50 value 190 ± 4.8 μM and compound 4c displayed promissing anti-inflammatory activity with IC50 value 48.31 ± 2.4 μM. Further, in cytotoxic activity, compound 4a, exhibhited siginificant potency on HepG2 and MIAPaCa-2 cell lines with IC50 values 14.68 ± 0.03 µM and 12.92 ± 1.4 µM respectively. To grasp the interaction between synthesized compounds and receptors related to their pharmacological property, these molecules were docked with Hypoxia-inducible factor 1-alpha (3KCY). [Display omitted]