Antimycotic action of a diamidine compound, 1, 4-bis-(m, m'-amidinophenoxymethyl)-cyclohexane dilactate, on Candida albicans.
The antimycotic action of 1, 4-bis-(m, m'-amidinophenoxymethyl)-cyclohexane dilactate (MAC), a synthetic diamidine compound, on Candida albicans was studied. The minimum inhibitory concentration (MIC) ranged from 3.31 to 6.25 micrograms/ml against both standard and clinically isolated strains. MAC was fungistatic at MIC and weakly fungicidal at the concentration of 100 micrograms/ml. MAC did not affect the cell wall or cause cell lysis. Intracellular constituents, such as 260 nm and 280 nm absorbing materials, were released from the cells by treatment with MAC indicating that MAC affected membrane permeability. The release of 260 nm absorbing material was inhibited by the presence of Ca2+ and Mg2+. Acidic phospholipids such as cardiolipin and phosphatidylglycerol inhibited the anti-Candida activity of MAC, but sterols and lecithin were not inhibitory, indicating that MAC interacted with acidic phospholipids of the cell membrane. Freeze-fracture electron microscopy showed that MAC caused aggregation of membrane particles and patch formation on the P face, which may indicate that MAC is a membrane disrupting agent. It appeared that MAC affected C. albicans at the cell membrane by interacting with acidic phospholipids and caused disorganization of the membrane structure resulting in the release of intracellular constituents without lysis.
D000578:Amidines / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001550:Benzamidines / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002462:Cell Membrane / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005614:Freeze Fracturing; D008854:Microscopy, Electron; D010743:Phospholipids / Q000494:pharmacology
D000578:Amidines; D000935:Antifungal Agents; D001550:Benzamidines; D010743:Phospholipids; C033076:1,4-bis(3,3'-amidinophenoxymethyl)cyclohexane dilactate