Synergistic antifungal effects of curcumin derivatives as fungal biofilm inhibitors with fluconazole

Abstract

Lack of novel antifungal agents and severe drug resistance has led to high incidence and associated mortality of invasive fungal infections. To tackle the challenges, novel antifungal agents with anti‐resistant potency are highly desirable. Thus, derivatives of curcumin were synthesized to restore the effectiveness of fluconazole (FLC) against FLC‐resistant Candida spp. and structure‐activity relationships were then discussed. Some novel derivatives showed promising features as novel antifungal lead compounds. Of them, compound 4 showed good alone or synergistic antifungal activity against FLC‐resistant Candida spp. Moreover, compound 4 was proven as a potent inhibitor of Candida albicans biofilm formation and yeast‐to‐hypha morphological transition whether used alone or in combination with FLC, which was further confirmed by the inhibitory effect on cellular surface hydrophobicity of C. albicans. Compound 4 also inhibits intracellular ATP production of C. albicans and disrupts membrane permeability of C. albicans when used in combination with FLC. The results highlighted the potential of curcumin derivatives to overcome fluconazole‐related and biofilm‐related drug resistance.

Cyclization of arylhydrazones of cross-conjugated enynones: synthesis of luminescent styryl-1H-pyrazoles and propenyl-1H-pyrazoles

“…3 Among them there are certain distinctive substances containing the 2-arylvinyl (styryl) group at various positions of a heterocycle, as well as their analogs. 4 Styrylpyrazoles, styrylpyrazolines and similarly structured substances possess antitumor, 5 antioxidative, 5 l,o ,6 antibacterial, 7 antimalarial, 8 antifungal, 9 and anti-inflammatory 10 properties, and some other types of biological activities 11 (also see the references in the review by Gomes and coworkers 4 for details). Furthermore, styrylpyrazoles have valuable photophysical abilities.…”

Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species

“…The satisfactory performance of curcumin against Candida biofilms has led to the use of this compound for inhibiting drug-resistant strains. In this regard, Dong et al (2021) used curcumin to restore the effectiveness of fluconazole against fluconazole-resistant Candida . Curcumin alone or in combination with fluconazole suppressed biofilm formation and yeast-to-hypha morphological transition in fluconazole-resistant C. albicans .…”

“…Furthermore, this compound combined with fluconazole disrupted membrane permeability and reduced intracellular ATPase production. The synergism of curcumin and fluconazole has introduced this compound as a new therapeutic agent against drug-resistant Candida strains ( Dong et al, 2021 ). However, there is limited data on the curcumin and antifungals interactions; thus, further studies are required.…”

Synergistic Antibiofilm Effects of Pseudolaric Acid A Combined with Fluconazole against Candida albicans via Inhibition of Adhesion and Yeast-To-Hypha Transition

“…Several phytochemicals have been found to potentially inhibit biofilm formation and, in combination with FLC, exhibit synergistic effects against C. albicans biofilms ( 9 ). For example, Dong et al found that a combination of curcumin derivatives and FLC showed synergistic antifungal activity against C. albicans biofilm formation ( 10 ). Pseudolaric acid A (PAA) is a diterpenoid extracted from a traditional Chinese medicine, the root bark of Pseudolarix kaempferi .…”