Interesting anticandidal effects of anisic aldehydes on growth and proton-pumping-ATPase-targeted activity

• Published in: Microbial pathogenesis Vol. 51; no. 4; pp. 277 - 284
• Main Authors: Shreaz, Sheikh, Bhatia, Rimple, Khan, Neelofar, Imran Ahmad, Sheikh, Muralidhar, Sumathi, Basir, Seemi F., Manzoor, Nikhat, Khan, Luqman A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2011; Elsevier India Pvt Ltd; Elsevier
• Subjects: acidification; adenosinetriphosphatase; aldehydes; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal properties; Benzaldehydes - chemistry; Benzaldehydes - pharmacology; benzene; Biological and medical sciences; Candida; Candida - cytology; Candida - drug effects; Candida - enzymology; Candida - growth & development; cell death; Fluconazole - pharmacology; Fundamental and applied biological sciences. Psychology; fungi; Humans; m-anisaldehyde; Microbial Sensitivity Tests; Microbiology; Microscopy, Electron, Scanning; Miscellaneous; Mycology; o-anisaldehyde; p-anisaldehyde; Plasma membrane H+-ATPase; Proton-Translocating ATPases - antagonists & inhibitors; protons; scanning electron microscopy; Structure-Activity Relationship; p-anisaldehyde; Plasma membrane H+-ATPase; m-anisaldehyde; Candida; o-anisaldehyde; Fungi; Yeast; Enzyme; Adenosinetriphosphatase; Plasma membrane; Hydrolases; Fungi Imperfecti; Plasma membrane H-ATPase
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2011.05.005

Attention has been drawn to evaluate the antifungal activity of p-anisaldehyde (1), o-anisaldehyde (2) and m-anisaldehyde (3). To put forward this approach, antifungal activity has been assessed in thirty six fluconazole-sensitive and eleven fluconazole-resistant Candida isolates. Growth and sensitivity of the organisms were significantly effected by test compounds at different concentrations. The rapid irreversible action of compound-1, compound-2 and compound-3 on fungal cells suggested a membrane-located target for their action. We investigated their effect on H+ ATPase mediated H+-pumping by various Candida species. All the compounds inhibit H+- ATPase activity at their respective MIC90 values. Inhibition of H+ ATPase leads to intracellular acidification and cell death. Scanning electron microscopy analysis revealed deep wrinkles, deformity and flowed content. Furthermore, it was also observed that position of methoxy group attached to the benzene ring decides antifungal activity of the compound. The present study indicates that compound-1, compound-2 and compound-3 have significant antifungal activity against Candida, including azole-resistant strains, advocating further investigation for clinical applications in the treatment of fungal infections. ► Anisic aldehydes exert their antifungal activity by targeting plasma membrane H+ ATPase activity. ► Inhibition of H+ ATPase leads to intracellular acidification and cell death. ► Position of methoxy group attached to the benzene ring decides antifungal activity of the structure. ► SEM analysis showed severe breakage of the Candida cell. ► Test compounds may thus be taken as an alternate to a novel anticandidal drug.