Complexes of oxoplatin with rhein and ferulic acid ligands as platinum(iv) prodrugs with high anti-tumor activity.

We herein designed two new Pt prodrugs of oxoplatin (cis,cis,cis-[PtCl(NH)(OH)]), [PtCl(NH)(OC-FA)] (Pt-2) and [PtCl(NH)(OC-RH)] (Pt-3), by conjugating with ferulic acid (FA-COOH) and rhein (RH-COOH) which have well-known biological activities. Three other Pt(iv) complexes of [PtCl(NH)(OC-BA)] (Pt-1), [PtCl(NH)(OC-CA)] (Pt-4) and [PtCl(NH)(OC-TCA)] (Pt-5) (where BA-COOH = benzoic acid, CA-COOH = crotonic acid and TCA-COOH = trans-cinnamic acid) were also prepared for the comparative study. Like most Pt prodrug complexes, the cytotoxicity of Pt-3 containing the biologically active rhein (RH-COOH) ligand against lung carcinoma (A549 and A549/DDP) cells was higher than those of Pt-1, Pt-2, Pt-4, cisplatin and Pt-5.

Novel Quinoline-based Ir(III) Complexes Exhibit High Antitumor Activity and .

Eight novel Ir(III) complexes listed as [Ir(H-P)(P)]PF (), [Ir(H-P)(dMP)]PF (), [Ir(H-P)(MP)]PF (), [Ir(H-P)(tMP)]PF (r), [Ir(MPy)(P)]PF (), [Ir(MPy)(dMP)]PF (), [Ir(MPy)(MP)]PF (), [Ir(MPy)((tMP)]PF () with 2-phenylpyri-dine () and 3-methyl-2-phenylpyridine () as ancillary ligands and pyrido-[3,2-]-pyrido[1',2':1,2]imidazo[4,5-]phenazine (), 12,13-dimethyl pyrido-[3,2-]-pyrido[1',2':1,2]-imidazo-[4,5-]-phenazine (), 2-methylpyrido [3,2-]-pyrido-[1',2':1,2]-imidazo-[4,5-]-phenazine (), and 2,12,13-trimethylpyrido-[3,2-]-pyrido-[1',2':1,2]-imidazo-[4,5-]-phenazine () as main ligands, respectively, were designed and synthesized to fully characterize and explore the effect of their toxicity on cancer cells. Cytotoxic mechanism studies demonstrated that the eight Ir(III) complexes exhibited highly potent antitumor activity selectively against cancer cell lines NCI-H460, T-24, and HeLa, and no activity against HL-7702, a noncancerous cell line. Among the eight Ir(III) complexes, exhibited the highest cytotoxicity with an IC = 5.

Strong in vitro and vivo cytotoxicity of novel organoplatinum(II) complexes with quinoline-coumarin derivatives.

A series of novel organoplatinum(II) complexes, [Pt(QC1)(H-QC1)Cl] (Pt1), [Pt(QC2)(H-QC2)Cl] (Pt2), [Pt(QC3)(H-QC3)Cl] (Pt3), [Pt(QC4)(H-QC4)Cl]⋅CHOH (Pt4), [Pt(QC5)(H-QC5)Cl] (Pt5), [Pt(H-QC6)(DMSO)Cl] (Pt6), [Pt(H-QC7)(DMSO)Cl]⋅HO (Pt7), [Pt(H-QC8)(DMSO)Cl] (Pt8), [Pt(H-QC9)(DMSO)Cl]⋅CHOH (Pt9), [Pt(H-QC10)(DMSO)Cl] (Pt10) and [Pt(H-QC11)(DMSO)Cl] (Pt11), bearing quinoline-coumarin derivatives (H-QC1-H-QC11) have been first designed. Complexes Pt1-Pt11 selectively displayed obvious cytotoxicities in comparison to cisplatin for A549/DDP (cisplatin-resistant human lung adenocarcinoma) cells and HeLa cervical carcinoma cells, with IC values as low as 100 nM-10.33 μM.

Two telomerase-targeting Pt(ii) complexes of jatrorrhizine and berberine derivatives induce apoptosis in human bladder tumor cells.

Two novel Pt(ii) complexes, [Pt(B-TFA)Cl]Cl (Pt1) and [Pt(J-TFA)Cl]Cl (Pt2) with jatrorrhizine and berberine derivatives (B-TFA and J-TFA) were first prepared as desirable luminescent agents for cellular applications and potent telomerase inhibitors, which can induce bladder T-24 tumor cell apoptosis by targeting telomerase, together with induction of mitochondrial dysfunction, telomere DNA damage and cell-cycle arrest. Importantly, T-24 tumor inhibition rate (TIR) was 50.4% for Pt2, which was higher than that of Pt1 (26.

High in vitro and in vivo antitumor activities of luminecent platinum(II) complexes with jatrorrhizine derivatives.

Two highly active anticancer Pt(II) complexes, [Pt(Jat1)Cl]Cl (Pt1) and [Pt(Jat2)Cl]Cl (Pt2), containing jatrorrhizine derivative ligands (Jat1 and Jat2) are described. Cell intake study showed high accumulation in cell nuclear fraction. Pt1 and Pt2 exhibited high selectivity for HeLa cancer cells (IC = 15.

Complexes of lanthanides(iii) with mixed 2,2'-bipyridyl and 5,7-dibromo-8-quinolinoline chelating ligands as a new class of promising anti-cancer agents.

Five novel lanthanides(iii) complexes, [Lu(Me)(MBrQ)2NO3] (MeMBrQ-Lu), [Ho(MeO)(MBrQ)2NO3] (MeOMBrQ-Ho), [Ho(Me)(MBrQ)2NO3] (MeMBrQ-Ho), [La(Me)2(BrQ)2NO3] (MeBrQ-La) and [Sm(Me)(BrQ)2(CH3OH)NO3] (MeBrQ-Sm), have been synthesized, in which 2,2'-bipyridyl (4,4'-dimethyl-2,2'-bipyridyl (Me) and 4,4'-dimethoxy-2,2'-bipyridine (MeO)) and 5,7-dibromo-8-quinolinoline derivatives (5,7-dibromo-2-methyl-8-quinolinol (MBrQ-H) and 5,7-dibromo-8-quinolinol (BrQ-H)) act as the chelating ligands. The in vitro cytotoxic activities of the five Ln(iii) complexes have been studied with the SK-OV-3/DDP, NCI-H460 and HeLa cancer cells. MeMBrQ-Lu, MeOMBrQ-Ho, MeMBrQ-Ho, MeBrQ-La and MeBrQ-Sm show higher cytotoxicity against the HeLa cells (IC50 values of 1.

In vitro and in vivo antitumor activities of three novel binuclear platinum(II) complexes with 4'-substituted-2,2':6',2″-terpyridine ligands.

Herein, we report the design and synthesis of three novel binuclear platinum(II) complexes, [Pt(tpbtpy)Cl][Pt(DMSO)Cl] (tpbtpy-Pt), [Pt(dthbtpy)Cl][Pt(DMSO)Cl]⋅CHOH (dthbtpy-Pt), and [Pt(qlbtpy)Cl][Pt(DMSO)Cl]⋅CHOH (qlbtpy-Pt) with 4'-(3-thiophenecarboxaldehyde)-2,2':6',2″-terpyridine (tpbtpy), 4'-(3,5-bis (1,1-dimethylethyl)-2-hydroxy-benzaldehyde)-2,2':6',2″-terpyridine (dthbtpy) and 4'-(2-quinolinecarboxaldehyde)-2,2':6',2″-terpyridine (qlbtpy) as ligands, respectively. All three novel binuclear platinum(II) complexes tpbtpy-Pt, dthbtpy-Pt, and qlbtpy-Pt were characterized by single-crystal X-ray diffraction analysis, spectroscopic analysis (ESI-MS, IR, H NMR), and elemental analysis. Additionally, the cytotoxicity of tpbtpy-Pt, dthbtpy-Pt and qlbtpy-Pt was assessed with human non-small cell lung cancer cell line (NCIH460 cells), yielding IC values in the range of 0.

Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function.

Four new platinum(ii) complexes, [Pt(Rut)(DMSO)Cl] (), [Pt(Try)(DMSO)Cl] (), [Pt(ITry)(DMSO)Cl] () and [Pt(BrTry)(DMSO)Cl] (), with rutaecarpine (Rut), tryptanthrin (Try), 8-iodine-tryptanthrin (ITry) and 8-bromo-tryptanthrin (BrTry) as ligands were synthesized and fully characterized. In these complexes, the platinum(ii) adopts a four-coordinated square planar geometry. The inhibitory activity evaluated by the MTT assay showed that (IC = of 0.

Synthesis of two platinum(II) complexes with 2-methyl-8-quinolinol derivatives as ligands and study of their antitumor activities.

Two platinum(II) complexes, [Pt(ClQ)(DMSO)Cl] (ClQ-Pt) and [Pt(BrQ)(DMSO)Cl] (BrQ-Pt), with 5,7-dichloro-2-methyl-8-quinolinol (H-ClQ) and 5,7-dibromo-2-methyl-8-quinolinol (H-BrQ) as ligands, respectively, have been synthesized and characterized. The single-crystal X-ray diffraction characterization as well as other spectroscopic and analytical studies of ClQ-Pt and BrQ-Pt revealed that the coordination geometry of Pt(II) can be described as a four-coordinated square planar geometry. By MTT assay, ClQ-Pt displayed the most potent activity, with IC values of 5.

Novel tacrine platinum(II) complexes display high anticancer activity via inhibition of telomerase activity, dysfunction of mitochondria, and activation of the p53 signaling pathway.

In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CHOH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)] (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'-dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10-phenanthroline (PTH), 2-(1-pyrenecarboxaldehyde) imidazo [4,5-f]-[1,10] phenanthroline (PIPTH), 2-picolylamine (PM) and 1,2-ethylenediamine (en) as telomerase inhibitors and p53 activators. Biological evaluations demonstrated that Pt1Pt7 exhibited cytotoxic activity against the tested NCIH460, Hep-G2, SK-OV-3, SK-OV-3/DDP and MGC80-3 cancer cell lines, with Pt5 displaying the highest cytotoxicity. Pt5 exhibited an IC value of 0.

Synthesis, characterization and biological evaluation of six highly cytotoxic ruthenium(ii) complexes with 4'-substituted-2,2':6',2''-terpyridine.

Herein, six ruthenium(ii) terpyridine complexes, [RuCl(4-EtN-Phtpy)(DMSO)] (), [RuCl(4-MeO-Phtpy)(DMSO)] (), [RuCl(2-MeO-Phtpy)(DMSO)] (), [RuCl(3-MeO-Phtpy)(DMSO)] (), [RuCl(1-Bip-Phtpy)(DMSO)] (), and [RuCl(1-Pyr-Phtpy)(DMSO)] () with 4'-(4-diethylaminophenyl)-2,2':6',2''-terpyridine (4-EtN-Phtpy), 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (4-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2''-terpyridine (2-MeO-Phtpy), 4'-(3-methoxyphenyl)-2,2':6',2''-terpyridine (3-MeO-Phtpy), 4'-(1-biphenylene)-2,2':6',2''-terpyridine (1-Bip-Phtpy), and 4'-(1-pyrene)-2,2':6',2''-terpyridine (1-Pyr-Phtpy), respectively, were synthesized and fully characterized. The MTT assay demonstrates that the anticancer activity of is higher than that of and more selective for Hep-G2 cells than for normal HL-7702 cells. In addition, various biological assays show that and , especially the complex, are telomerase inhibitors targeting c-myc G4 DNA and also cause apoptosis of Hep-G2 cells.

Design, synthesis and pharmacological evaluation of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives as potential antitumor agents.

A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a-5d) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that 5a exhibited effective inhibition on tumor growth in the NCI-H460 xenograft mouse model and that 5d displayed excellent antiproliferative activity in the BEL-7402 xenograft model.

Synthesis and antitumor mechanisms of two novel platinum(ii) complexes with 3-(2'-benzimidazolyl)-7-methoxycoumarin.

Two novel platinum(ii) complexes, [PtCl2(H-MeOBC)(DMSO)] (Pt1) and [Pt2Cl3(MeOBC)(DMSO)2] (Pt2), with 3-(2'-benzimidazolyl)-8-methoxycoumarin (H-MeOBC) as the ligand were synthesized and evaluated for their antiproliferative activity. Among all the tumor cells, dual-Pt(ii) complex Pt2 exhibited the most potent activity, with an IC50 value of 0.5 ± 0.

Synthesis, Characterization, and Cytotoxicity of the Cobalt (III) Complex with N,N-Diethyl-4-(2,2':6',2''-terpyridin-4'-yl)aniline.

A cobalt(III) complex, [Co(L) ](ClO ) (1), in which the ligand L was N,N-diethyl-4-(2,2':6',2''-terpyridin-4'-yl)aniline (L), was synthesized and fully characterized. This new cobalt(III) complex 1 exhibited selective cytotoxicity against HeLa, T-24, A549, MGC80-3, HepG2, and SK-OV-3 cells with IC values in the micromolar range (0.52 - 4.

Synthesis, crystal structure and biological evaluation of a new dasatinib copper(II) complex as telomerase inhibitor.

A new copper(II) complex of dasatinib (DAS) was synthesized and characterized via ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction analysis, H and C NMR spectroscopy, and elemental analysis. The composition of the new complex (1) was found to be [Cu(DAS + H)(NO)(HO)]NO·(HO)·(CHOH). Through MTT assay, it was found that 1 had high cytotoxicity towards A549, HeLa, BEL-7402, Hep-G2, NCI-H460, and MGC80-3 tumor cell lines, with IC values in 4.

Synthesis and in vitro biological evaluation of three 4'-(4-methoxyphenyl)-2,2':6',2″-terpyridine iridium(III) complexes as new telomerase inhibitors.

There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl] (1), [Ir(2-MeO-Phtpy)Cl] (2) and [Ir(4-MeO-Phtpy)Cl] (3) with 4'-(3-methoxyphenyl)-2,2':6',2″-terpyridine (3-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2″-terpyridine (2-MeO-Phtpy) and 4'-(4-methoxyphenyl)-2,2':6',2″-terpyridine (4-MeO-Phtpy) as ligands, respectively, were synthesized and evaluated for their antiproliferative activities. In these complexes, the iridium(III) center adopts a six-coordinate distorted octahedral geometry. Among them, complex 1 exhibited the most potent activity, with IC values of 3.

Synthesis and antitumor mechanism of a new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol as ligands.

A new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol (HClMQ) as ligands, , [Fe(ClMQ)Cl] (), was synthesized and evaluated for its anticancer activity. Compared to the HClMQ ligand, complex showed a higher cytotoxicity towards a series of tumor cell lines, including Hep-G2, BEL-7404, NCI-H460, A549, and T-24, with IC values in the range of 5.04-14.