Processes, Vol. 14, Pages 409: New Dual-Action Azoles: Synthesis and Biological Evaluation of Cytocompatible Candidates for Topical Wound Therapy

Processes doi: 10.3390/pr14030409

Authors:
Alina-Georgiana Cristea (Hohotă)
Alina Viorica Iancu
Rodica Tatia
Maria Luisa di Gioia
Claudia-Simona Stefan
Ionut Dragostin
Elena-Lăcrămioara Lisă
Oana-Maria Dragostin

Wound healing is a complex process essential for maintaining skin integrity; however, the rise of antibiotic-resistant bacteria limits therapeutic options, highlighting the critical need for new antimicrobial agents. In this context, this research focused on the synthesis of new azole derivatives and their biological evaluation, specifically targeting antimicrobial, antioxidant, and biocompatible properties relevant to wound infections. In the present work, ketoconazole derivatives were obtained through an initial reaction with an excess of hydrazine hydrate, followed by condensation with benzaldehydes and cyclization with chloroacetyl chloride to form a β-lactam ring. These compounds were evaluated in vitro for antioxidant activity using FRAP, DPPH, and TAC assays, and for antimicrobial activity against a variety of microorganisms. Additionally, the cytotoxicity was assessed using the MTT assay on a normal mouse fibroblast cell line (NCTC, clone L929) for evaluating the biocompatibility of the obtained compounds. Derivative K1 exhibited the highest antioxidant activity, a finding confirmed by all three assays. Regarding antimicrobial properties, all compounds demonstrated notable activity, with K1, K4 and K5 displaying superior efficacy. Significantly, the MTT assay revealed that the derivatives exhibit dose-dependent cytotoxicity but maintain favorable safety profiles at therapeutic concentrations, supporting their suitability for topical application. In conclusion, these findings suggest that the synthesized derivatives may serve as promising leads for infected wound therapy. Future research will further explore the therapeutical potential of these compounds, together with their incorporation into polymeric films designed for chronic wound treatment.

Source link

Alina-Georgiana Cristea (Hohotă) www.mdpi.com