XI Simpósio Brasileiro de Química Teórica
Caxambu, 18 a 21 Novembro de 2001
 
 
 
 

P168

ARTEMISININ DERIVATIVES WITH ANTIMALARIAL ACTIVITY
AGAINST PLASMODIUM falciparum DESIGNED WITH AID OF
QUANTUM CHEMICAL AND PARTIAL LEAST SQUARES
 METHODS

José Ciríaco Pinheiro (PQ), Oscar A. S. Romero (PQ)
DQ, CCEN, UFBA,
66075-110 Belém, PA, Brasil
E-mail: ciriaco@ufpa.br
   Marlon M. dos Reis (PG), Márcia M. C. Ferreira PQ)
 DFQ, IQ, UNICAP
13081-970 Campinas, SP, Brasil

          Malaria has been known  since  the  earliest  times.   Hippocratic  in  his  writings
has  already  mentioned  different  manifestations   of   that   disease   and   called   the
attention  for  one  of  its  characteristic  symptoms,   the  enlargement   of   the  spleen.¹
There  are  four  members   of   the   Plasmodium   gender   that   infect   humans  and
all are transmitted through the female bite of the Anophelese mosquito.  However, most
of  the  deaths  is  attributed  to  the parasite  species  falciparum.   The severity of the
disease cause by this species result primarily from its ability to modify the surface
of  infected  red  blood  cells  by  inserting  parasite  proteins.²
          Among  the  classes  of  drugs  that  areeffective in  the  clinical  treatment  of  the
falciparum malaria,    we   have   the  artemisinin    or   quinghaosu    and  a  variety  of
derivatives.   This compound  is  a  sesquiterpene  containing    the  1,2,4-trioxane   ring
and was originally extracted from the herb Artemisina annua L. or Qing hao used for the
treaement of 52 kinds of diseases in People's Rebublic of China.^3,4
          In this work, Quantum Chemical and  Partial  Least  Squares  (PLS)  methods are
employed  in  the  design  of  artemisinin  derivatives  with  antimalarial  activity   against
Plasmodium  falciparum  resistant  to  mefloquine. Initially compounds of literature are
studied using t he  Hartree-Fock/6-31G* method.   The  PLS  metthod  is  then u sed  to
build a multivariave modelans  and  prediction of  the  unknown  antimalarial activity,  of
new artemisinin derivatives.
          The  PLS  analysis  using three latent variables explained 96.29% of  X  variance
and the most important descriptors for the design  of  the  model  were  one level above
the  lowest   occupied   molecular   orbital (LUMO+1),   atomic  charge  on  atoms,  and
WHIM-3D index, related  to  the  molecular  symmetry:  axis 1, weight:  electronegativity
(G1e)

CNPq/FAPESP
____________________________________________________________________
1 A. R. Butler, Y.-L. Wu, Chem. Soc. Rev. 21 (1992) 85.
2 S. Bowman et al., Nature 400 (1999) 532.
3 D. L. Klayman, Science 228 (1985) 1049.
4 J. C. Pinheiro, M. M. C. Ferreira, O. A. S. Romero, J. Mol. Struct. (THEOCHEM), in
press.