Rosselli F. P., Ferreira M. M. C., Albuquerque C. N., da Silva A. B. F., “A Structure-Activity Relationship (SAR/QSAR) Study of Analogous Compounds of Megazol with Activity Against Trypanosoma cruzi”. Caxambu, MG, Brazil, 04-06/11/2002: XXIX Annual Meeting on Basic Research in Chagas Disease and XVIII Meeting of the Brazilian Society of Protozoology. Rev. Inst. Med. Trop. S. Paulo, 44 (Suppl. 12) 12, November 2002. Poster CT-25.

CT25   -  A  STRUCTURE-ACTIVITY  RELATIONSHIP  (SAR/QSAR)  STUDY  OF
ANALOGOUS   COMPOUNDS   OF   MEGAZOL   WITH   ACTIVITY   AGAINST
Trypanosoma cruzi

Rosselli, F. P. (PG)^a, Ferreira, M. M. C. (PQ)^b, Albuquerque, C. N. (PQ)^c, da Silva, A. B.
F. (PQ)^a

a Instituto de Química de São Carlos, Departamento de Química e Física Molecular - USP,
Caixa Postal 780, São Carlos - SP;
b Instituto de Química - UNICAMP, Campinas - SP;
c Departamento de Tecnologia Bioquímico-Farmacêutica (FTB), Faculdade de Ciências
frosselli@iqsc.usp.br

The Chagas disease,  caused  by  protozoan Trypanosoma  cruzi,  reaches  about  ¼  of
population  of  Latin  America,  representing  one  of  more  important  medical-sanitary
problems in 17 countries, including Brazil.  It is estimated that 16 to 18 million people are
infected  by  the  parasite.  It´s  the  only  infectious  disease  among   the large Brazilian
endemics, that doesn´t have efficient treatment. Furthermore, it is included in 6 endemic
parasitic diseases recognized like priority by World Health Organization (WHO).
One class of chemical compounds, the nitroimidazoles, has been calling the attention due
to its excellent anti-parasitary activity and, within this class, the megazol, whose chemical
name  is   1-methyl-2-(5-amino-1,3,4-thiadiazole)-5-nitroimidazole,  showed  a  notable
activity  against  the  T. cruzi.  However,  posterior  studies,  made  in vivo  and  in vitro,
demostrated the strongly mutagenic feature of megazol.  So,  new  derived compounds of
the megazol have been synthesized by the researcher Cristina Nothfleet Albuquergue. She
intends  to seek drugs as more active the  megazol,  but with lower mutagenic character
than  it or,  if  possible,  devoid  of  toxicity.  In  the  present  work,  it  was  tried to settle a
relationship   between   biological   activitiy   against   T.  cruzi  (tripanocial  activity  or
antichagasic activity)  showed for megazol  and  some  analogous  compounds  -  activities
were obtained by in vitro tests - with structural and physical chemistry properties for these
compounds (a study of SAR/QSAR). These properties (variables or descriptors), which can
be  didactically shared in steric, electronic, lipophilicity  and  polarizability properties,  were
calculated by quantum mechanic methods (ab initio), from molecular package  AMPAC 5.0
program. It was calculated about 50 variables.
Then,  to  process  these  data,  we made use of  statistical  methodologies  -  like  Principal
Component  Analysis  (PCA),   Hierarchical  Cluster  Analysis  (HCA)   and   Kth  Nearest
Neighbor (KNN),  available in  Piroutte 2.0 program  -  to obtain a relationship between the
calculated  variables  and  degree  of  tripanocidal  activity,  with  the  aim  to  separate  the
megazol plus its analogous compounds into two groups: compounds with higher activity
and  compounds  with  lower  activity.  It  was  also  tried  to  use  multivariate  regression
methods,  like Partial Least Squares  (PLS).
Agência Financiadora: CAPES
 
 
 
 
 
 
 
 
 

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