ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Novel heterocyclic coumarin annulates: synthesis and figuring their roles in biomedicine, bench-to-bedside investigation

Nameer Mazin Zeki and Yasser Fakri Mustafa

Department of Pharmacology, College of Medicine, Ninevah University, Mosul, Iraq

E-mail: Nameer.zeki@uoninevah.edu.iq

Received: 1 March 2024  Accepted: 21 March 2024

Abstract:

This study revealed the first synthesis of seven novel coumarins annulated with heterocycle composed of four heteroatoms, one sulfur, and three oxygen atoms in a linear pattern. This is an effort to find readily available coumarin frameworks with a broad variety of biological properties that are both adjustable and easy to get. The synthetic annulates' structural framework was confirmed by means of spectroscopic techniques, which included ¹H-NMR, ¹³C-NMR, and FTIR. The synthesized annulates were investigated in vitro for their biomedical potential as antioxidative stress, anti-inflammatory, antidiabetic, anticancer, and antimicrobial agents. In addition, their biosafety toward nontumor cells and commensal bacterial strains was also assessed in vitro. Computer-aided programs were employed to explore the toxicity and pharmacokinetic profiles of the synthesized annulates. Based on the findings that were obtained, the authors stated the following main outcomes. There have been promising and far-reaching biological effects of the synthesized heterocyclic coumarin annulates. HC1 demonstrated strong anti-inflammatory potential through the lipoxygenase-dependent route. Moreover, HC1 exhibited significant antifungal efficacy, surpassing that of nystatin. HC2 held great promise as an antioxidative stress, anticancer, and biosafe candidate. HC3 exhibited a strong antibacterial potential against all tested aerobic bacterial strains, demonstrating a potency equivalent to that of ciprofloxacin. In addition, all of the synthesized annulates, especially HC3, exhibited a noteworthy biosafety profile against the commensal bacterial strains. The strong inhibitory capabilities of HC6 and HC7 toward glucosidase and amylase indicate that they possess great promise as antidiabetic agents. Finally, the synthesized annulates showed favorable toxicity and oral bioavailability properties. It can be inferred that these annulates have the potential to be useful frameworks for developing new drugs with a broad spectrum of bioactivity in the coming years.

Keywords: Annulation; Biosafety; Coumarin; Drug-likeness; Heterocycle; Multiactivity

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03441-2

Chemical Papers 78 (8) 4935–4951 (2024)