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Central European Journal of Medicine

, Volume 1, Issue 4, pp 370–378 | Cite as

The α 1-adrenolytic and structural evaluation of new pyridoindole derivatives

  • Magdaléna Májeková
  • Vladimír Šnirc
  • Svorad Štolc
  • Pavol Májek
  • Želmíra Bezáková
  • Ružena Sotníková
Research Article
  • 26 Downloads

Abstract

α 1 — adrenolytic activities of pyridoindole derivatives recently synthesized in the Institute of Experimental Pharmacology, Slovak Academy of Sciences, were measured. A characteristic set of derivatives (five active, one with a threshold activity and two inactive) was chosen and an elementary structure-activity study was performed. The structure and energy properties were estimated by quantum-chemical semiempirical AM1 and molecular mechanics methods. The ionization constants pKα of the individual derivatives were calculated by program Pallas or estimated by potenciometric titration. The α 1 blocking activities were measured by rat thoracic aorta model. The experimental model used was not α 1 — adrenoreceptor subtypes specific, however, the α 1D subtype could be considered to be a predominant type in a rat aorta. The obtained physico-chemical parameters were then compared with the blocking activities of the derivatives and following determining characters for α 1 — adrenolytic activities were determined: 1) the polarity of the substituted phenol ring represented by a map of molecular electrostatic potential and 2) the hexahydro-pyridine nitrogen pKα constant, which represents the ability of the compound to be protonated by physiologic pH.

Keywords

α1-adrenolytic activity pyridoindole structure-activity AM1 method 

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Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Magdaléna Májeková
    • 1
  • Vladimír Šnirc
    • 1
  • Svorad Štolc
    • 1
  • Pavol Májek
    • 2
  • Želmíra Bezáková
    • 3
  • Ružena Sotníková
  1. 1.Institute of Experimental PharmacologySlovak Academy of SciencesBratislavaSlovakia
  2. 2.Department of Pharmaceutical Chemistry, Faculty of PharmacyComenius UniversityBratislavaSlovakia
  3. 3.Department of Analytical Chemistry, Faculty of Chemical and Food TechnologySlovak Technical UniversityBratislavaSlovakia

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