外文资料Conformational Analysis of Epiquinine and Epiquinidine.pdfVIP

c Structural Chemistry, Vol. 12, No. 6, December 2001 ( 2001) Conformational Analysis of Epiquinine and Epiquinidine Thais H. A. Silva,1 Ala´ıde B. Oliveira,1 H´elio F. Dos Santos,2 and Wagner B. De Almeida34 Received April 19, 2001; revised May 16, 2001; accepted May 18, 2001 The conformational potential energy surfaces for the epiquinine and epiquinidine molecules were analyzed in gas phase and water solution using semiempirical and ab initio levels of theory. The results obtained showed that the main conformation of the nonactive threo epimers is distinct from those observed for the active parent compounds quinine and quinidine. This result might be used, on a qualitative way, to understand the loss of activity of the threo epimers and allow selecting important conformations to be considered in molecular modeling quantitative studies addressing the drug–receptor interactions. KEY WORDS: Conformational analysis; antimalarial; epiquinine; epiquinidine. INTRODUCTION the antimalarial activity [3]. The three-dimensional struc- tures of the Cinchona alkaloids have been examined in Malaria is one of the greatest human health problems order to explain the differences in activities between the because of its high incidence. Over 40% of the world pop- 9-epialkaloids 3,4 and quinine 1 and quinidine 2. ulation in 99 countries are living under risk of contract-