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 equiperdum”. 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-26.

CT26   -  A  STRUCTURE-ACTIVITY  RELATIONSHIP  (SAR/QSAR)  STUDY  OF
ANALOGOUS   COMPOUNDS   OF   MEGAZOL   WITH   ACTIVITY   AGAINST
Trypanosoma equiperdum

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 protozoan Trypanosoma equiperdum is the causative agent of  the disease  known as
dourine (or durin). It´s a contagious disease that happens in horses and asses, and it takes
place mainly in Africa.  It's  transmitted from host to host during the copulation,  becoming
usually chronic. Acute signs are characterized by augment (inflammantion) of genital organ.
Furthermore, it appears edematous subcutaneous plaques, light and intermittent fever,
progressional paralysis  of posterior members, emaciation and death.
In 1995, Cristina Northfleet Albuquerque, by occasion of her doctorate, synthesized some
analogous compounds, the megazol,  chemically 1-methyl-2-(5-amino-1,3,4-thiadiazole)-5-
nitroimidazole.  Her main intention has been the Trypanosoma cruzi and Chagas disease,
but some of her compounds were tested against T. equiperdum too. A study of structure-
activity  relationship  (QSAR/SAR)  tries  to  settle  a  relationship  between  molecular
properties and biological activities. In this work, it was tried to related molecular properties
(variables or descriptors)  of the megazol plus some of its analogous compounds and their
biological  activities,  which  were  acquired  from  in vitro  tests.  The molecular properties
(variables or descriptors), which can be didactically shared in steric, electronic, lipophilicity
and polarizability properties, were calculated by quantum mechanic methods (ab initio). It
was calculated about 50 molecular descriptors,  through computational package  AMPAC
5.0  program.   In  the  next  step,   statistical   techniques  were  employed  to  reduce  the
 dimensionality  of   the  dataset  and  investigate  which  variable  subset  would be more
effecting in classifying the compounds studied in two groups, according to their degreee of
activity  against  T. equiperdum:  compounds  with  higher  activity  and with lower activity
against  T. equiperdum.   This  classification   is  obtained  through  pattern  recognition
techniques, such as  principal  component  analysis  (PCA),  hierarchical  cluster  analysis
(HCA)  and  Kth  nearest  neighbor  (KNN), available in  Piroutte 2.0 program.  It was also
tried to use multivariate regression method. like partial least-squares method  (PLS).

Agência Financiadora: CAPES
 
 
 
 
 
 
 
 
 

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