title: Identification of human telomerase inhibitors having the core of N-acyl-4,5-dihydropyrazole with anticancer effects.
abstract: Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2 Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06 ± 0.17 and 2.89 ± 0.62 μM, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86 ± 0.51 μM, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA:DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a-8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase.
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ni
authors.affiliation: School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan 243002, China.
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Jia
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China.
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Xu
authors.affiliation: Research Center for Drug Discovery and Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address: czliao@hfut.edu.cn.
authors.forename: Chenzhong
authors.initials: C
authors.lastname: Liao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D019098:Telomerase
keywords: Anticancer; Dihydropyrazole; Molecular modeling; Telomerase; Telomerase inhibitor