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Conformational analysis of the antimalarial agent quinine


Quinine, an active antimalarial compound, is one of the most abundant constituents extracted from the bark ofCinchona trees. The activity differences among structurally related molecules appear to depend on the absolute stereochemistry of some functional groups, a result that has stimulated a detailed conformational analysis of these molecules of biological interest. In the present study the potential energy surface (PES) for the antimalarial agent quinine (C20H24O2N2) has been comprehensively investigated using the molecular mechanics (MM) and quantum mechanical semiem-pirical AM1 and PM3 methods. Six distinct minimum-energy structures are located on the multidimensional PES and also characterized as true minima through harmonic frequency analysis. The relative stabilities and thermodynamic properties are reported. The coexistence of different conformers is discussed for the first time in the literature based on the calculated transition-state (TS) structures connecting the six minima located on the PES for the quinine molecule. The theoretical results reported in the present study are in agreement with the experimental proposal, based on NMR data, that there are two possible forms for the quinine molecule in solution.

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Correspondence to Wagner B. De Almeida.

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Silva, T.H.A., Oliveira, A.B. & De Almeida, W.B. Conformational analysis of the antimalarial agent quinine. Struct Chem 8, 95–107 (1997).

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Key words

  • Conformational analysis
  • antimalarial
  • quinine