title: Synthesis, molecular modeling and biological evaluation of N-benzylidene-2-((5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide derivatives as potential anticancer agents.
abstract: A series of new 1,3,4-oxadiazole derivatives (6a-6x) containing pyridine and acylhydrazone moieties were synthesized and developed as potential telomerase inhibitors. The bioassay tests demonstrated that compounds 6n, 6o, 6q, 6s and 6t exhibited significant broad-spectrum anticancer activity with IC₅₀ range from 0.76 to 9.59 μM against the four cancer cell lines (HEPG2, MCF7, SW1116 and BGC823). Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. Compound 6s showed the highest anticancer activity with IC₅₀ of 0.76-1.54 μM against the tested cancer cell lines and exhibited the most potent telomerase inhibitory activity with IC₅₀ of 1.18 ± 0.14 μM. The docking simulation was carried out to investigate a possible binding mode of compound 6s into the active site of telomerase (pdb. 3DU6) while the QSAR model was built to check the previous work as well as to introduce new directions.
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: She-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: botanyzh@163.com.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010069:Oxadiazoles
keywords: 1,3,4-Oxadiazole; 3D-QSAR; Acylhydrazone; Anticancer activity; Molecular docking; Pyridine; Telomerase inhibitor