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Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents.
Comput Biol Chem. 2018 Oct; 76:151-160.CB

Abstract

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 R1 position and less bulky amines group at R2 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 R2 point of 1,3,4-oxadiazole-2-thione moiety is essential for anticancer activity.

Authors+Show Affiliations

SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India.SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India.SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, A Central University, Bilaspur, 495009, Chhattisgarh, India, India. Electronic address: jagadishpharm09@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30015176

Citation

Bajaj, Shalini, et al. "Synthesis, Thymidine Phosphorylase Inhibitory and Computational Study of Novel 1,3,4-oxadiazole-2-thione Derivatives as Potential Anticancer Agents." Computational Biology and Chemistry, vol. 76, 2018, pp. 151-160.
Bajaj S, Roy PP, Singh J. Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents. Comput Biol Chem. 2018;76:151-160.
Bajaj, S., Roy, P. P., & Singh, J. (2018). Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents. Computational Biology and Chemistry, 76, 151-160. https://doi.org/10.1016/j.compbiolchem.2018.05.013
Bajaj S, Roy PP, Singh J. Synthesis, Thymidine Phosphorylase Inhibitory and Computational Study of Novel 1,3,4-oxadiazole-2-thione Derivatives as Potential Anticancer Agents. Comput Biol Chem. 2018;76:151-160. PubMed PMID: 30015176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, thymidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadiazole-2-thione derivatives as potential anticancer agents. AU - Bajaj,Shalini, AU - Roy,Partha Pratim, AU - Singh,Jagadish, Y1 - 2018/05/16/ PY - 2018/03/05/received PY - 2018/05/11/revised PY - 2018/05/13/accepted PY - 2018/7/18/pubmed PY - 2018/10/13/medline PY - 2018/7/18/entrez KW - 1,3,4-oxadiazole-2-thione KW - Anticancer activity KW - Docking KW - MCF-7 KW - Thymidine phosphorylase SP - 151 EP - 160 JF - Computational biology and chemistry JO - Comput Biol Chem VL - 76 N2 - 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 R1 position and less bulky amines group at R2 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 R2 point of 1,3,4-oxadiazole-2-thione moiety is essential for anticancer activity. SN - 1476-928X UR - https://www.unboundmedicine.com/medline/citation/30015176/Synthesis_thymidine_phosphorylase_inhibitory_and_computational_study_of_novel_134_oxadiazole_2_thione_derivatives_as_potential_anticancer_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1476-9271(18)30131-2 DB - PRIME DP - Unbound Medicine ER -