title: Novel 2-pyridinecarboxaldehyde thiosemicarbazones Ga(III) complexes with a high antiproliferative activity by promoting apoptosis and inhibiting cell cycle.
abstract: Two types of 2-pyridinecarboxaldehyde thiosemicarbazones Ga(III) complexes, which are 2:1 and 1:1 ligand/Ga(III) complexes, were synthesized and determined by X-ray single crystal diffraction. The antiproliferative activity of these Ga(III) complexes have been examined to illuminate the structure-activity relationships essential to form Ga(III) complexes with remarkable anticancer activity. In addition, Ga(III) complexes where the metal/ligand ratio was 1:1 (C4) had observably higher antiproliferative activity than 1:2 (C3). Ga(III) complexes caused a marked increase of caspase-3 and 9 activity in NCI-H460 cells compared to the metal free ligand. Caspase activation was somewhat mediated by the release of Cyt C from mitochondria after incubation with selected agents. Both types of Ga(III) complexes showed more effective in inhibition of the G1/S transition than the ligand alone.
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China; Qinzhou University, 12 Binhai Avenue, Qinzhou, Guangxi, China.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Qi
authors.affiliation: Affiliated Hospital, Guilin Medical College, 15 Lequn Road, Guilin, Guangxi, China.
authors.forename: Jungang
authors.initials: J
authors.lastname: Deng
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tian
authors.affiliation: Qinzhou University, 12 Binhai Avenue, Qinzhou, Guangxi, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Li
authors.affiliation: Qinzhou University, 12 Binhai Avenue, Qinzhou, Guangxi, China.
authors.forename: Kunhuan
authors.initials: K
authors.lastname: He
authors.affiliation: Qinzhou University, 12 Binhai Avenue, Qinzhou, Guangxi, China.
authors.forename: Xueren
authors.initials: X
authors.lastname: Huang
authors.affiliation: Stanford Cancer Institute, Member of Academic Council, Stanford University, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Qinzhou University, 12 Binhai Avenue, Qinzhou, Guangxi, China. Electronic address: yunyunjinxu@163.com.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China. Electronic address: yihongwang@seu.edu.cn.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005708:Gallium / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011725:Pyridines; D013882:Thiosemicarbazones; C051439:pyridinecarboxaldehyde; D005708:Gallium; D053148:Caspase 3; D053453:Caspase 9
keywords: Anti-cancer mechanism; Cell apoptosis; Cell cycle; Gallium (III); Thiosemicarbazone