E. B de Melo, M. M. C. Ferreira, A. T. Bruni, "Conformational Systematic Analysis of 5CITEP, a Lead Compound for the Development of HIV-Integrase Enzyme Inhibitors". Rio de Janeiro, RJ, Brazil, 22-25/11/2004: The 2nd Brazilian Symposium on Medicinal Chemistry: Current Trends in Drug Discovery and Development. Abstract Book, (2004) 40. Poster S1-32. Session 1 (S1): Drug Discovery and Development: Sci-Mix.

Key words: HIV-integrase, 5CITEP, conformational systematic analysis
The etiological agent of AIDS is the retrovirus HIV.   A possible new therapeutic target being studies is the HIV-integrase enzyme  (IN),
responsible for the proviral DNA entrance into genetic material from the host.   An inhibitor 5CITEP/integrase crystallographic complex
was recently reported  by  Goldur  et al.  (PDB:  1QS4).   The objective of this trial is to perform a QSAR study based  on  diverse  b-
diketones that show integrase inhibition activity.   There  is no report on the  present-day  literature regarding conformational studies  of
such compounds.  Firstly, the enol structure of the lead compound 5CITEP was optimized at AM1 level.   A systematic conformational
analysis was carried out by rotating the two free angles.  The increments were  30º,  and  for later refinements  5º  and  1º.  The  global
minimum conformation is featured by 356º in the angle q₂  (between keto-enol group and indole ring) and  0º  in q₁ (between keto-enol
group and tetrazole ring). The inhibitor geometry in the active site was somewhat different from the obtained global minimum, and  this
difference vanished when the experimental geometry was optimized by AM1.
 
 

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