دورية أكاديمية
Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents.
| العنوان: | Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents. |
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| المؤلفون: | Bajaj S; SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India., Roy PP; SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India., Singh J; SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India. Electronic address: jagadishpharm09@gmail.com. |
| المصدر: | Computational biology and chemistry [Comput Biol Chem] 2018 Oct; Vol. 76, pp. 151-160. Date of Electronic Publication: 2018 May 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 101157394 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-928X (Electronic) Linking ISSN: 14769271 NLM ISO Abbreviation: Comput Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Original Publication: Oxford : Pergamon, c2003- |
| مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , Oxadiazoles/*pharmacology , Thiones/*pharmacology , Thymidine Phosphorylase/*antagonists & inhibitors, Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Catalytic Domain ; Enzyme Assays ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacokinetics ; Enzyme Inhibitors/pharmacology ; Humans ; MCF-7 Cells ; Molecular Docking Simulation ; Oxadiazoles/chemical synthesis ; Oxadiazoles/chemistry ; Oxadiazoles/pharmacokinetics ; Structure-Activity Relationship ; Thiones/chemical synthesis ; Thiones/chemistry ; Thiones/pharmacokinetics ; Thymidine Phosphorylase/chemistry |
| مستخلص: | A series of novel 1,3,4-oxadiazole-2-thione derivatives were designed, synthesized and evaluated for in vitro anticancer activity against breast cancer (MCF-7) cell line and thymidine phosphorylase. The synthesis of target compounds was performed by cyclization reaction using aromatic amines and carbon disulphide to get mannich bases. The synthesized compound 2j exhibited the most potent anticancer activity against MCF-7 cell line. Compounds 2d, 2j, 2o and 2h showed potent thymidine phosphorylase inhibitory activity. The SAR study revealed that the substitution of phenyl ring with electron withdrawing group at R 1 position and less bulky amines group at R 2 position of 1,3,4-oxadiazole-2-thione ring showed significant growth inhibitory activity. Further in silico ADMET properties of synthesized compounds were calculated along with molecular docking to study the binding mode of the compounds in the active site of thymidine phosphorylase (TP). The molecular docking studies showed that amines group have good binding interaction on active site residues of TP such as compounds 2j and 2o exhibited hydrogen bond interaction with amino acid residues GLY152, THR151 and HIS116 of thymidine phosphorylase (PDB ID: 1UOU). The result of biological activity and docking study revealed that amines group at R 2 point of 1,3,4-oxadiazole-2-thione moiety is essential for anticancer activity. (Copyright © 2018. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: 1,3,4-oxadiazole-2-thione; Anticancer activity; Docking; MCF-7; Thymidine phosphorylase |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Enzyme Inhibitors) 0 (Oxadiazoles) 0 (Thiones) EC 2.4.2.4 (Thymidine Phosphorylase) |
| تواريخ الأحداث: | Date Created: 20180718 Date Completed: 20181012 Latest Revision: 20181012 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.compbiolchem.2018.05.013 |
| PMID: | 30015176 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1476-928X |
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| DOI: | 10.1016/j.compbiolchem.2018.05.013 |