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The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1 – 6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate. Non-anionic-cationic type Gd(III) complex 1 , which exhibited hight cytotoxicity to towards T24 cells and low cytotoxicity towards HL-7702 cells, induced T24 cells arrest in the G2 phase and apoptosis via a mitochondrial dysfunction pathway. Unlabelled Image • Six new rare earth complexes with quinolinyl hydrazine were synthesized. • Complex 1 exhibited selective cytotoxicity to tumor cells versus HL-7702 cells. • Complex 1 caused T24 cell apoptosis via a mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Six pyrazolopyrimidine Rh (III)/Pd(II) complexes were prepared and exhibited excellent cytotoxic activity, complex 5 and 6 induced cell cycle arrest, apoptosis and ER stress, suppressed cells proliferation in vivo. [Display omitted] • Six pyrazolopyrimidine Rh(III)/pd(II) complexes were synthesized and characterized. • Structure activity relationship (SAR) of the complexes was studied. • Complexes 1 – 6 exhibited excellent antitumor activity against various tumor cells. • Complexes 5 and 6 induced cell cycle arrest, apoptosis and ER stress. • Complex 5 and 6 inhibited the growth of T-24 in vivo. Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H 2 O)Cl 3 ] (1), [Rh(L2)(CH 3 OH)Cl 3 ] (2), [Rh(L3)(H 2 O)Cl 3 ] (3), [Rh 2 (L4)Cl 6 ]·CH 3 OH (4), [Rh(L5)(CH 3 CN)Cl 3 ]·0.5CH 3 CN (5), and [Pd(L5)Cl 2 ] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6. [ABSTRACT FROM AUTHOR]

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC 50 value of 0.5 μM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by −NO 2 significantly enhanced the anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds 4 , 4B and 4V , suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24. [Display omitted] • One-pot reaction for synthesis of oxoaporphine alkaloids was developed. • A series of oxoaporphine alkaloids were synthesized. • 4B induced DNA damage, and caused significant G2/M cell cycle arrest. • 4B induced caspase-3/9-dependent apoptosis through mitochondrial dysfunction. • 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24. [ABSTRACT FROM AUTHOR]