Design and Synthesis of Organic Dyes Incorporating Thiadiazole Moieties for Enhanced Antifungal Applications

Abstract

The growing incidence of drug-resistant fungal infections has intensified the search for novel antifungal agents built on bioactive heterocyclic scaffolds. In this study, we designed two hybridized thiadiazole-based azo dyes, HD1 and HD2, synthesized via diazotization and coupling reactions, and evaluated their antifungal potential. The dyes were obtained in good yields, HD1: 75% and HD2: 80%, displayed sharp melting points, 232–236 °C and 225–230 °C, respectively, and exhibited distinct colorations, purple for HD1 and brown for HD2, consistent with pure, well-conjugated chromophoric systems. FT-IR spectroscopy confirmed the successful incorporation of key functional groups, including carbonyl, 1681.8–1748.8 cm⁻¹, hydroxyl, 3424.7–3514.9 cm⁻¹, and azo, –N=N–, 1581.7–1599.9 cm⁻¹ stretching bands, while UV–Visible analysis revealed absorption maxima at 520 nm for HD1 and 540 nm for HD2, indicative of effective donor–acceptor conjugation across the thiadiazole–azo framework. Antifungal activity was assessed against Candida albicans, Candida tropicalis, and Aspergillus niger using the agar well diffusion method, with fluconazole as the reference drug, followed by determination of the minimum inhibitory concentration, MIC, and minimum fungicidal concentration, MFC. Both dyes displayed dose-dependent inhibition; HD2 consistently produced larger inhibition zones, up to 31 mm against A. niger at 100 mg/mL, than HD1, up to 28 mm, approaching the activity of fluconazole, 34 mm. MIC determination confirmed the superior potency of HD2, which inhibited all test organisms at 12.5 mg/mL, whereas HD1 required 25 mg/mL against C. albicans. MFC values established fungicidal action at 12.5 mg/mL for A. niger and C. tropicalis with HD2, with higher concentrations required against C. albicans. These results show that hybridizing the thiadiazole nucleus with azo chromophores yields dual-function compounds that combine useful colorant properties with promising antifungal activity, and that subtle substituent modifications significantly modulate potency.