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Comparative analysis of the distribution of the molecular electrostatic potential for cholesterol and ergosterol

1994; Elsevier BV; Volume: 311; Linguagem: Inglês

10.1016/s0166-1280(09)80066-3

1872-7999

Maciej Bagiński, P. Bruni, E. Borowski,

Molecular Junctions and Nanostructures

The selective toxicity of the antifungal antibiotic amphotericin B is based on a difference in the affinity of the drug for its cellular targets in fungal and mammalian cells which are membrane-located ergosterol and cholesterol, respectively. The affinity forces comprise van der Waals interactions and hydrogen bonding systems. The comparative analysis of the distribution of the molecular electrostatic potential (MEP) for both sterols was carried out to provide the data for a better understanding of the molecular basis for the preferential binding of amphotericin B to ergosterol compared with cholesterol. The MEP was calculated by the semiempirical CNDO/2D method for one selected conformer of each sterol. The calculations were performed on different planes and presented in the form of maps. The analysis performed revealed the qualitative differences between cholesterol and ergosterol in the distribution of the MEP around the side-chain of the sterols. Similarities in the distribution of the MEP were also found near the hydroxyl group and the ring A of the sterols. The differences found between the electrostatic patterns of the cholesterol and ergosterol molecules can be regarded as a source of the higher affinity of amphotericin B for ergosterol than for cholesterol which is observed experimentally. Our results support the hypothesis of a molecular model of a polyene—sterol complex derived earlier from the experimental data of Hervé et al.