Interference with effects of amphotericin B on Candida albicans cells by 2-chloroethyl-1-nitrosoureas

Abstract

Two nitrosoureas, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), with strong carbamoylating and weak alkylating activities, interfered with the induction of potassium leakage and lethal action of amphotericin B (AmB) on Candida albicans. 2-Cyclohexyl isocyanate, the product of decomposition of CCNU, and 2-chloroethyl isocyanate, the product of decomposition of BCNU, also interfered with the anticandidal actions of AmB. In contrast, two nitrosoureas with weak carbamoylating and strong alkylating activities, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperydyl)-1-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose, did not affect AmB action against C. albicans. These results indicate that the inhibitory action of CCNU and BCNU on the anticandidal effects of AmB is associated with the carbamoylating activity of these nitrosoureas.