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Effects of Acridine Derivatives on Ca²⁺ Uptake by Candida albicans

Martha Calahorra*, Norma Silvia Sanchez and Antonio Pena

The effects of several acridine derivatives, and chloroquine, which has a similar lateral chain to quinacrine, but with a quinoline nucleus, were studied on a strain of Candida albicans. Parameters estimated were: a) dichloromethane/water partition coefficients; b) uptake by cells; c) effects on respiration, d) effects on the acidification of the medium; e) efflux of K+; f) uptake of 86Rb+ and 45Ca²⁺, and d) effects on growth of cells. Results obtained in general: a) most of them showed a low hydrophobicity; b) most of them were significantly taken up by cells; c) acridine orange, acridine yellow, quinacrine and nonyl acridine orange inhibited respiration; d) acridine orange, quinacrine and nonyl acridine orange inhibited acidification of the medium. The most significant finding was that acridine orange, quinacrine and nonyl acridine orange at 60 μM or 120 μM, and acriflavine at 120 μM produced an efflux of K+, an inhibition of 86Rb+ uptake, and a remarkable many fold increase of 45Ca²⁺ uptake. Acridine orange and acridine yellow produced only a decrease of duplication time; with the concentrations used, only nonyl acridine orange inhibited growth. It is suggested that quinacrine may be used as an adjuvant or topical agent against candidiasis. Chemical derivatives of some of the dyes might also be used against pathogenic fungi.