Kiralj R., Ferreira M.M.C., “A COMBINED CHEMOMETRIC, STRUCTURAL, MOLECULAR GRAPHICS AND MODELING STUDY OF PROGESTOGENS”. Caxambu, MG, Brazil, 11-16/11/2001: 1º Simpósio Brasileiro em Química Medicinal, QSAR e Modelagem Molecular: Novas Estratégias em Planejamento Racional de Fármacos [1st Brazilian Symposium on Medicinal Chemistry, QSAR and Molecular Modeling: New Approaches in Drug Design]. Oral & Poster APM20. Section: 4. Applications of Multivariate QSAR.

Progestogens

Name
       Rudolf Kiralj

Institution/Company
      Instituto de Química, Universidade Estadual de Campinas

Country
      Brasil

First Abstract Title
      A COMBINED CHEMOMETRIC, STRUCTURAL, MOLECULAR GRAPHICS AND MODELING STUDY OF
      PROGESTOGENS

First Abstract
      M. M. C. Ferreira, R. Kiralj, Instituto de Química, Universidade Estadual de Campinas, Campinas, SP, 13083-970,
      Brazil.

      Keywords: Progestogens.

      Progesterone and progestogens are known not only as contraceptives but also as potential drugs for hormonal,
      anti-cancer and other therapies, and in veterinary practice. The lack of larger number and homogenicity of
      biological activity data makes it difficult to have a clear picture of the progestogens behaviour at atomic
      level. The crystal structure of progesterone-receptor complex¹ gave much insight into such an intermolecular
      interaction. Continuing the SAR study² on two sets of progestogens, a combined study including Partial Least
      Squares (PLS), structural studies employing related crystal structures, molecular graphics and modeling of
      progestogen-receptor was performed. Besides DFT ab initio computed molecular descriptors two more types were
      used: a priori³ and molecular graphics&modeling descriptors. All the methodologies confirmed steric, electronic and
      hydrophobic properties of progestogens being responsible for activity. Besides, progestogen heteroaromaticity and
      conformational properties including resonance effects, substituent position and characteristics are phenomena both
      described well by molecular descriptors and visualized by molecular graphics. Related crystal structures confirm the
      basic principles on progestogen-receptor binding.

      1 S. P. Williams, P. B. Sigler, Nature 393 (1998) 392-396.
      2 R. Vendrame, M. C. Ferreira, C. H. Collins, Y. Takahata, J. Mol. Graph. Mod. 19 (2001), in press.
      3 R. Kiralj, M. M. C. Ferreira, J. Mol. Graph. Mod., submitted for publication.

      FAPESP