Effects of Acridine Derivatives on Ca2+ Uptake by Candida albicans

Abstract

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 45Ca 2+ , 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 45Ca 2+ 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.

Influence of phenothiazines, phenazines and phenoxazine on cation transport inCandida albicans

“…As already seen with acridine derivatives (Calahorra et al . ), all dyes (120 μ mol l −1 ) inhibited Rb + transport except for the Zn salt of toluidine blue and acridine orange. So the possibilities are that dyes bind to the cell membrane affecting its function and leading to K + efflux, or directly bind to the K + transporter inhibiting the entrance of Rb + , or shielding the negative charges of the membrane.…”

“…So we tested two agents known by their capacity to increase Ca 2+ transport in yeast: quinacrine (Calahorra et al . ) and amiodarone (Courchesne and Ozturk ) at a 50 μ mol l −1 concentration, adding variable toluidine blue‐ZnCl 2 concentrations (Fig. a) or ZnCl 2 (Fig.…”

“…These studies were performed as part of an exploration of the effects of several dyes on S. cerevisiae , of which already some results have been published (Calahorra et al . ). Experiments were started with MB, one of the first dyes used against malaria at the end of the 19th century (Guttman and Ehrlich ) whose effects were also studied in yeast by Armstrong ().…”

“…Another possibility would be considering the basic structure of some of the agents reported here and before (Calahorra et al . ) to design more effective antifungals.…”

“…Recent work in our laboratory was focused on the effects of acridine derivatives on Candida albicans (Calahorra et al . ); although most of them do not affect growth, some did cause a large increase in Ca 2+ uptake. From these results we doubt whether the increased Ca 2+ uptake, caused by dye exposure, can induce apoptosis and cells death as described by other authors (Courchesne and Ozturk ; Muend and Rao ; Maresova et al .…”