Synthesis, in vitro antifungal evaluation and in silico study of 3-azolyl-4-chromanone phenylhydrazones

Abstract

BackgroundThe currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives.MethodsThe 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2'-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents.ResultsThe in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 μg/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score.ConclusionThe 3-azolyl-4-chromanone phenylhydrazones considered as analogs of 3-azolyl-4-chromanone oxime ethers basically designed as antifungal agents. The antifungal activity of title compounds was comparable to that of standard drug fluconazole. The drug-likeness data of synthesized compounds make them promising leads for future development of antifungal agents.

Synthesis, In silico studies and In vitro evaluation for antioxidant and antibacterial properties of diarylmethylamines: A novel class of structurally simple and highly potent pharmacophore

“…OSIRIS Property Explorer was used to estimate the risks of side effects, such as mutagenic, tumorigenic, irritant and reproductive effects, as well as drug-relevant properties including cLogP (lipophilicity), LogS (solubility), drug-likeness and overall drug-score (Ayati et al, 2012).…”

Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests

“…Although effective antifungal agents are currently available, side effects such as toxicity, drug interactions, inadequate pharmacokinetic properties and the development of resistance have been reported [2]. Therefore, new active entities that are safer, more potent and broad spectrum are highly desired as antifungal agents.…”

Design, synthesis, and biological activities of novel azole-bonded $$\upbeta $$ β -hydroxypropyl oxime O-ethers

“…The search for new antifungals structurally related to fluconazole still continues [10,[22][23][24][25]. Moreover, some oxiconazole analogs are potent antifungal agents having oxime ether group in their structures [26][27][28][29][30][31][32].…”