Antifungal activity of Some Synthetic Heterocyclic Thiophene and Pyrimidine Derivatives

The currently available antifungal drugs have the limitations of toxicity and development of resistance. Hence, the development of new less toxic antifungal agents is urgently required. This study aimed to evaluate the antifungal potential of eight synthetic pyrimidines and thiophene derivatives for the first time using in vitro assays against six common fungal pathogens. Six of the examined derivatives showed moderate to high antifungal activity against the tested pathogenic fungal strains. Compound C3 (2-Aminonaphtho[2,1-b]thiophene-1-carbonitrile) was the most effective as it strongly inhibited all the tested fungal strains. It exhibited fungicidal activity (MFC/MIC Ratio ≤ 4) against both M. canis AUMC11663 (MIC=31µg/mL and MFC=125µg/mL), and T. mentagrophytes AUMC11661 (MIC=125µg/mL and MFC=125µg/mL). Whereas, this compound had a fungistatic effect (MFC/MIC Ratio > 4) against the rest. Compound C4 (2-Aminoindeno[2,1-b]thiophene-3-carbonitrile) showed a potent fungicidal activity against each of T. mentagrophytes AUMC11661 (MIC=31µg/mL and MFC=31µg/mL) and C. albicans AUMC9142 (MIC=31µg/mL and MFC=63µg/mL), while it had a fungistatic effect against A. fumigatus AUMC51. Compound C5 (5,6,10-Trihydronaphtho[1′, 2′:4,5]thieno[2,3-d]pyrimidin-11-one) had also fungicidal effects against T. mentagrophytes AUMC11661 (MIC=31µg/mL and MFC=63µg/mL) and M. canis AUMC11663 (MIC=31µg/mL and MFC=31µg/mL) but it showed a slight fungistatic activity against T. rubrum AUMC1804. The remaining compounds exhibited fungistatic activities against some of the tested strains. The evaluation of cytotoxicity of the most potent compound (C3) revealed the safety of its active concentrations. Thus, this study suggests that 2-Aminonaphtho[2,1-b] thiophene-1-carbonitrile (C3) is a promising thiophene derivative for the development of a novel safe effective and broad-spectrum antifungal drug.