QSAR study of pyrazolo[4,3-e][1,2,4]triazine sulfonamides against tumor-associated human carbonic anhydrase isoforms IX and XII

Comput Biol Chem. 2017 Dec:71:57-62. doi: 10.1016/j.compbiolchem.2017.09.006. Epub 2017 Sep 21.

Abstract

The QSAR models for a set of pyrazolo[4,3-e][1,2,4]triazines incorporating benzenesulfonamide moiety combined directly with the heterocyclic ring or by NH linkage were generated. The inhibitory potency of compounds against human carbonic anhydrase isoforms IX and XII and antiproliferative activity against human MCF-7 cells were used as the dependent variables. The Codessa pro software was used for the descriptors calculation and the Best Multi-Linear Regression (BMLR) algorithm was employed to build the QSAR models. It was found that quantum descriptors are critical of the compounds activities. The selected models have good predictive accuracy confirmed by a set of the statistical quantities recommended by OECD.

Keywords: Carbonic anhydrase; MLR; Molecular descriptor; Pyrazolotriazine sulfonamide; QSAR.

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Cell Survival / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Quantitative Structure-Activity Relationship*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Triazines
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • carbonic anhydrase XII