3D-QSAR study on heterocyclic topoisomerase II inhibitors using CoMSIA

Tekiner-Gulbas B., ARPACI Ö., YILDIZ İ., Aki-Sener E., Yalcin I.

SAR AND QSAR IN ENVIRONMENTAL RESEARCH, cilt.17, sa.2, ss.121-132, 2006 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 2
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1080/10659360600636105
  • Dergi Adı: SAR AND QSAR IN ENVIRONMENTAL RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.121-132
  • Anahtar Kelimeler: 3D-QSAR, CoMSIA, topoisomerase II inhibitors, benzoxazoles, benzimidazoles, benzothiazoles, oxazolo(4,5-b)pyridines, MOLECULAR SIMILARITY INDEXES, FIELD ANALYSIS, DNA TOPOISOMERASES, BINDING, COMFA, DERIVATIVES, LIGANDS, SINGLE, YEAST
  • Ankara Üniversitesi Adresli: Evet

Özet

Selective topoisomerase II (Topo II) inhibitors have interested to a great extent for the design of new antitumoral compounds in recent years. Comparative molecular similarity indices analysis (CoMSIA) was performed on a series of previously synthesized benzoxazole, benzimidazole, and oxazolo(4,5-b) pyridine derivatives as eukaryotic Topo II inhibitors. A training set of 16 heterocyclic compounds was used to establish the CoMSIA model. They were constructed and geometrically optimized using SYBYL v7.0. The predictive ability of the model was assessed using a test set of 7 compounds. The best model has demonstrated a good fit having r(2) value of 0.968 and cross-validated coefficient q(2) value as 0.562 including steric and hydrophobic fields. The hydrophobic interactions showed a dominant role for increasing Topo II inhibitor activity and hydrophilic substituent was found more important than hydrophobic one on the 5 or 6 position of benzazole moiety. The model obtained from the present study can be useful for the modification and/or evaluation of the development of new Topo II inhibitors as potential antitumor compounds.