Applied Chemical Engineering

Novel 1,3-dioxolane–coumarin hybrids: From synthesis to pharmacological In Vitro-In Silico profiling

Duha Adnan Hassan

Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq

Yasser Fakri Mustafa

Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq

DOI: https://doi.org/10.59429/ace.v8i1.5651

Keywords: hybridization; 1,3-dioxolane; biosafety; coumarin; drug-likeness; multi-target therapeutics

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Abstract

In this study, we report the design, synthesis, and comprehensive biological evaluation of a novel series of linear 1,3-dioxolane–coumarin hybrids (DCH1–DCH7) as promising multi-target therapeutic agents. The synthesis involved an optimized multi-step approach beginning with a Pechmann condensation followed by selective esterification reactions, yielding high-purity compounds confirmed via FTIR, ¹H-NMR, and ¹³C-NMR analyses. The hybrids were systematically screened for their antioxidant, anticancer, anti-inflammatory, antidiabetic, and antimicrobial activities. In addition, their biocompatibility was assessed using non-cancerous human cell lines and commensal bacterial strains. Among the synthesized hybrids, DCH4 exhibited remarkable antioxidant and anticancer properties, while DCH1 showed superior anti-inflammatory and antifungal activity. DCH2 demonstrated potent antidiabetic and anti-anaerobic bacterial efficacy, and DCH5 emerged as the most active against aerobic gram-negative bacteria. These bioactivities were closely linked to specific structural modifications, as revealed through structure–activity relationship analyses. In silico evaluations using ProTox-II, PreADME, and SwissADME tools predicted favorable drug-likeness, low toxicity, high oral bioavailability, and acceptable pharmacokinetic profiles, further supporting their therapeutic relevance. Importantly, all hybrids displayed minimal cytotoxic effects on non-cancerous cells and exhibited selective antimicrobial actions, sparing beneficial gut microbiota. This highlights their potential as safer alternatives to conventional therapies. The introduction of the 1,3-dioxolane moiety into the coumarin scaffold contributed significantly to the observed bioactivities, suggesting this hybrid framework as a versatile platform for future drug development. Overall, our findings establish these 1,3-dioxolane–coumarin hybrids as promising multifunctional drug candidates with broad-spectrum pharmacological potential and a strong safety profile, warranting further investigation and development.

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