Synthesis and Biological Evaluation of Novel 2-Aminonicotinamide Derivatives as Antifungal Agents.

Based on the structures of the reported compounds G884 [N-(3-(pentan-2-yloxy)phenyl)nicotinamide], E1210 [3-(3-(4-((pyridin-2-yloxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-amine], and 10 b [2-amino-N-((5-(3-fluorophenoxy)thiophen-2-yl)methyl)nicotinamide], which inhibit the biosynthesis of glycosylphosphatidylinositol (GPI)-anchored proteins in fungi, a series of novel 2-aminonicotinamide derivatives were designed, synthesized, and evaluated for in vitro antifungal activity. Most of these compounds were found to exhibit potent in vitro antifungal activity against Candida albicans, with MIC values ranging from 0.0313 to 4.

[Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans].

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS.

Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.

Berberine inhibits fluphenazine-induced up-regulation of CDR1 in Candida albicans.

Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C.

Structural optimization of berberine as a synergist to restore antifungal activity of fluconazole against drug-resistant Candida albicans.

We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. A structure-activity relationship study of 95 analogues led us to identify the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a-l, which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound 7 d (N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(2-fluorophenyl)acetamide) significantly decreased the MIC₈₀ values of fluconazole from 128.