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Quantitative Structure–Activity Relationship and Combinatorial Design of 1,3,4-Oxadiazole-Based Thymidine Phosphorylase Inhibitors as Potential Anti-Cancer Agents


Affiliations
1 SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India
 

The 3D quantitative structure–activity relationship model representing r2 = 0.8605, q2 = 0.8193 and pred_r2 = 0.6847 respectively, was generated for thymidine phosphorylase (TP) inhibitory activity of some 1,3,4-oxadiazole derivatives. Electronegative substituents at R1 and less steric bulk with electropositive substituents at R2 were found to be favourable for TP inhibition. The activity prediction of a combinatorial library of 1629 compounds resulted in 50 molecules whose predicted activity was comparable to the most active compound in the dataset and within the model’s applicability domain. Among them six molecules showed favourable interactions with the active site of TP proposing potential anticancer activity of the title compounds.

Keywords

Anti-Cancer Therapy, Docking, Combinatorial Library, 1,3,4-Oxadiazole, 3D-QSAR.
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  • Quantitative Structure–Activity Relationship and Combinatorial Design of 1,3,4-Oxadiazole-Based Thymidine Phosphorylase Inhibitors as Potential Anti-Cancer Agents

Abstract Views: 309  |  PDF Views: 83

Authors

Shalini Bajaj
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India
Piyush Ghode
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India
Jagadish Singh
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India
Partha Pratim Roy
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India
Sanmati Kumar Jain
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, India

Abstract


The 3D quantitative structure–activity relationship model representing r2 = 0.8605, q2 = 0.8193 and pred_r2 = 0.6847 respectively, was generated for thymidine phosphorylase (TP) inhibitory activity of some 1,3,4-oxadiazole derivatives. Electronegative substituents at R1 and less steric bulk with electropositive substituents at R2 were found to be favourable for TP inhibition. The activity prediction of a combinatorial library of 1629 compounds resulted in 50 molecules whose predicted activity was comparable to the most active compound in the dataset and within the model’s applicability domain. Among them six molecules showed favourable interactions with the active site of TP proposing potential anticancer activity of the title compounds.

Keywords


Anti-Cancer Therapy, Docking, Combinatorial Library, 1,3,4-Oxadiazole, 3D-QSAR.

References





DOI: https://doi.org/10.18520/cs%2Fv114%2Fi10%2F2063-2071