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Our previous studies have demonstrated that BML284 is a colchicine-site tubulin degradation agent. To improve its antiproliferative properties, 45 derivatives or analogs of BML284 were designed and synthesized based on the cocrystal structure of BML284 and tubulin. Among them, 5i was the most potent derivative, with IC 50 values ranging from 0.02 to 0.05 μM against the five tested tumor cell lines. Structure-activity relationship studies verified that the N1 atom of the pyrimidine ring was the key functional group for its tubulin degradation ability. The 5i-tubulin cocrystal complex revealed that the binding pattern of 5i to tubulin is similar to that of BML284. However, replacing the benzodioxole ring with an indole ring strengthened the hydrogen bond formed by the 2-amino group with E198, which improved the antiproliferative activity of 5i. Compound 5i effectively suppressed tumor growth at an intravenous dose of 40 mg/kg (every 2 days) in paclitaxel sensitive A2780S and paclitaxel resistant A2780T ovarian xenograft models, with tumor growth inhibition values of 79.4% and 82.0%, respectively, without apparent side effects, showing its potential to overcome multidrug resistance. This study provided a successful example of crystal structure-guided discovery of 5i as a colchicine-targeted tubulin degradation agent, expanding the scope of targeted protein degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Six positional isomers of triptolide-glucose conjugates (TG1α, TG1β, TG2, TG3, TG4 and TG6) were designed and synthesized. These conjugates exhibited better water solubility, and had selective cytotoxicity between tumor cells with high expression of glucose transport-1 (Glut-1) and non-tumor cells with low expression of Glut-1, in which TG2 formed by triptolide (TPL) and d-glucose C2-OH had the strongest cytotoxicity to tumor cells and lowest toxicity in non-tumor cells, therefore the highest relative therapeutic index, which was 5.7 times that of triptolide and consequent the most powerful selective antitumor activity in vitro. The cytotoxicity of TG2 was highly correlated with Glut-1 function. As a prodrug of triptolide, TG2 could promote RNA Pol II degradation and induce apoptosis as TPL does. TG2 had a stronger dose-dependent antitumor effect in vivo than TPL and no adverse reaction occurred when its tumor inhibition was higher than 90%, which was associated with its selective distribution in tumor tissues. TG2 could be used as a promising drug candidate for the treatment of solid tumors with high expression of Glut-1, which is worthy of further study., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Topoisomerases are interesting targets for drug discovery. In the present study, we attached saturated carbon atoms to the 10-position of camptothecin and synthesized 10 new camptothecin derivatives from 10-HCPT or SN-38. The activities of new compounds were evaluated both in vitro and in vivo. The most promising compound F10, 7-ethyl-10-(2-oxo-2-(piperidin-1-yl)ethoxy)camptothecin, inhibited cancer cells growth with the IC 50 of 0.002, 0.003, 0.011 and 0.081 μM on Raji, HCT116, A549 and Lovo cells, respectively. Meanwhile, oral administration of F10 remarkably suppressed the HCT116-xenograft tumor growth in the nude-mice model at the dosage of 0.5, 2.0 and 8.0 mg/kg in vivo. Intraperitoneal administration of F10 can completely inhibit Raji-xenograft tumor growth in established NPG mouse model at 2.0 and 4.0 mg/kg. In addition, the minimum lethal doses of F10 and SN-38 in mice by intravenous administration were 80 and 40 mg/kg (or 0.155, 0.102 mmol/kg), respectively. The solubility of F10 reached 9.86 μg/mL in a buffer solution of pH 4.5. The oral bioavailability of F10 achieved 22.4% in mice. The molecular docking model revealed that F10 can interact with topoisomerase I-DNA complex. Our findings indicate that F10 is a new orally-oavailable antitumor agent with potent anticancer effect. Furthermore, attaching a ring hydrophobic moiety to the 10-position of camptothecin provides a favorable approach in the optimization of camptothecin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Epidermal growth factor receptor (EGFR), a member of the HER family, is closely related to the development of multiple cancers. Herein, we report the discovery of small molecule EGFR degraders based on the proteolysis targeting chimera (PROTAC) strategy. In the present study, 13 EGFR degraders containing pyrido[3,4-d] pyrimidine moiety were designed and synthesized. Promising PROTACs 2 and 10 induced degradation of EGFR in HCC827 cells with the DC 50 values of 45.2 and 34.8 nM, respectively. Cellular protein-controlling machinery ubiquitin proteasome system (UPS) was involved in the degradation process. Furthermore, the degraders 2 and 10 could significantly induce the apoptosis of HCC827 cells and arrest the cells in G 1 phase. These findings demonstrated that compounds 2 and 10 could serve as effective EGFR del19 -targeting degraders in HCC827 cells. v., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Targeting L858R/T790M/C797S mutant EGFR is a major challenge in the new-generation EGFR tyrosine kinase inhibitors development for conquering drug resistant NSCLC. In this study, a series of novel 9-heterocyclyl substituted 9H-purine derivatives were designed as EGFR L858 R/T790 M/C797S tyrosine kinase inhibitors. Among these compounds, D4, D9, D11 and D12 showed significantly potent anti-proliferation and EGFR L858 R/T790 M/C797S inhibition activity. In particular, the most potent compound D9 showed anti-proliferation against HCC827 and H1975 cell lines with the IC 50 values of 0.00088 and 0.20 μM, respectively. And D9 inhibited the EGFR L858 R/T790 M/C797S with an IC 50 value of 18 nM. Furtherly, D9 could significantly suppress the EGFR phosphorylation, induce the apoptosis, arrest cell cycle at G0/G1, and inhibit colony formation in HCC827 cell line by a concentration-dependent manner. Molecular docking indicated that the introduction of a cyclopropylsulfonamide group in D9 led to the formation of additional two hydrogen bonds with mutant Ser797 which played key roles in generating efficient EGFR L858 R/T790 M/C797S inhibitory activity. These findings strongly indicated that 9-heterocyclyl substituted 9H-purine derivatives were promising L858R/T790M/C797S mutant EGFR-TKIs. The introduction of extra hydrogen bond interaction with mutant Ser797 is efficient method for the design of the fourth-generation EGFR-TKIs., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Mcl-1 is an anti-apoptotic member of Bcl-2 family proteins. The development of inhibitors of Mcl-1 has been challenging. To develop metal-based Mcl-1inhibitors, twenty two copper(II) complexes 25-46 with 9-substituted β-carboline derivatives were reported. Complexes 38 and 39 showed higher cytotoxicity than the corresponding ligands or cisplatin. The most potent complex 39 presented higher selectivity to Mcl-1 than other Bcl-2 family proteins, and killed cancer cells via Bax/Bak mediated apoptosis. Complex 39 showed an excellent safety profile in mouse model, and significantly inhibited the tumor growth in NCI-H460 tumor bearing model, which is more potent than AZD5991 at the same dosage. Complex 39 prolonged the survival time of the tumor bearing mice. Complex 39 is the first metal-based Mcl-1 inhibitor acting as a potential anticancer agent., (Crown Copyright © 2019. Published by Elsevier Masson SAS. All rights reserved.)

Ganglioside GM3, belonging to glycosphingolipid family, has been known as tumor-associated carbohydrate antigen on several types of tumor. Many studies have revealed that GM3 plays a role in cell proliferation, adhesion and differentiation, which is crucial in the process of cancer development. In the present study, we firstly synthesized novel mannose-containing GM3 analogues by enzymatic hydrolysis and chemical procedures. Then the antiproliferative activity of the novel analogues along with galactose-containing analogues we prepared previously was investigated and the data demonstrated that these analogues exhibited antiproliferative effect on K562 and HCT116 cells. Finally, the influence of these analogues on tumor cell migration was studied on B16, B16-F10 and HCCLM3 cells by wound healing test, because the migration of tumor cells represents one of the relevant factors in assessing the malignancy of cancer. This study could lay the foundation for optimizing leading compounds and provide valuable information for finding new antitumor drugs for cancer therapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Two gold(III) complexes of isoquinoline derivatives: [Au(L 1 )Cl 2 ] (Au1) and [Au(L 2 )Cl 2 ] (Au2) have been prepared and characterized. Au1 and Au2 exhibited greater cytotoxicity than their corresponding ligands and cisplatin against T-24 cells. Both complexes arrested cell cycle at S-phase by upregulation of p53, p27, and p21, and downregulation of cyclin A and cyclin E. The depolarization of the mitochondrial membrane potential, generation of ROS, and stimulated Ca 2+ release activated the caspase cascade and ultimately caused apoptosis by increasing the levels of Bax and Bak, and decreasing the levels of Bcl-2 and Bcl-xl. Cell apoptosis was achieved via mitochondria mediated pathways. The in vivo studies of Au1 and Au2 demonstrated that they were safer than cisplatin and could effectively inhibit tumor growth., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

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 50 values of 5.02-34.38 μM against MGC80-3, T-24, Hep-G2 and BEL-7402 tumor cells. Among them, the T-24 cells the highest sensitivity to ClQ-Pt and BrQ-Pt with IC 50 value of 5.02 ± 0.62 μM and 18.02 ± 1.05 μM, respectively. In addition, ClQ-Pt caused a higher percentage of apoptotic T-24 cells (ca. 33.75%) than that of BrQ-Pt (ca. 23.85%) and cisplatin (ca. 12.82%). Mechanistic studies revealed that ClQ-Pt and BrQ-Pt caused T-24 cell cycle arrest at the S phase, as shown by the down-regulation of cyclin A and CDK2 expression levels. In addition, ClQ-Pt and BrQ-Pt also caused mitochondrial dysfunction. Interestingly, the in vitro anticancer activity of ClQ-Pt was higher than those of BrQ-Pt and cisplatin, more selective for T-24 tumor cells than for normal HL-7702 cells. Taken together, we concluded that the 5- and 7-substitution groups of the ClQ ligands play an important role in determining the anti-proliferation activity of the corresponding Pt(II) complexes., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CH 3 OH (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 50 value of 0.13 ± 0.16 μM against SK-OV-3/DDP cancer cells and significantly reduced tumor growth in a Hep-G2 xenograft mouse model (tumor growth inhibition (TGI) = 40.8%, p < 0.05) at a dose of 15.0 mg/kg. Interestingly, Pt1Pt7 displayed low cytotoxicity against normal HL-7702 cells. Mechanistic studies revealed that these compounds caused cell cycle arrest at the G2/M and S phases, and regulated the expression of CDK2, cyclin A, p21, p53 and p27. Further mechanistic studies showed that Pt5 induced SK-OV3/DDP cell apoptosis via dysfunction of mitochondria, inhibition of the telomerase activity by directly targeting the c-myc promoter, and activation of the p53 signaling pathway. Taken together, Pt5 has the potential to be further developed as a new antitumor drug., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

A new copper(II) complex of dasatinib (DAS) was synthesized and characterized via ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction analysis, 1 H and 13 C NMR spectroscopy, and elemental analysis. The composition of the new complex (1) was found to be [Cu(DAS + H)(NO 3 ) 2 (H 2 O)]NO 3 ·(H 2 O)·(CH 3 OH). 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 50 values in 4.04-13.04 μM. The Hep-G2 cells were the most sensitive to 1. It is worth noting that compared with DAS and cisplatin, 1 not only had higher in vitro anticancer activity but also exhibited greater selective toxicity towards Hep-G2 cells than for normal HL-7702 cells. Experimental results from cell apoptosis analysis, cellular uptake, TRAP-silver staining assay, RT-PCR, western blot, and transfection assays showed that 1 was most likely a telomerase inhibitor that targeted c-myc G-quadruplex DNA. The high cytotoxicity and biological behaviors of 1 could be correlated with the central copper(II) atom in the coordinated mode with DAS., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 μM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Two metal complexes of NiLCl2 (1) and [PtLCl]Cl (2) with 4-([2,2':6',2″-terpyridin]-4'-yl)-N,N-diethylaniline (L) were synthesized and characterized. 1 and 2 exhibited selective cytotoxicity to T-24 cells more than L, compared with the normal liver cell line (HL-7702). Various experiments showed that L, 1 and 2 caused T-24 cell cycle arrest at S phase, as shown by the down-regulation of cdc25 A, cyclin A, cyclin B and CDK2 and the up-regulation of p21, p27 and p53. Furthermore, complexes 1 and 2, especially complex 2, acted as telomerase inhibitors targeting c-myc G-quadruplex DNA and triggered cell apoptosis. In addition, 1 and 2 also caused mitochondrial dysfunction. Taken together, we found that 1 and 2 exerted their cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and disruption of mitochondrial function., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Three transition metal complexes with isoquinoline derivatives: [(MPDQ)2Zn(C2H5OH)ClO4]ClO4 (1) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP)2Zn(H2O)](ClO4)2 (2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ)2Ni(CH3OH)ClO4]ClO4 (3) were synthesized and fully characterized. All complexes exhibited strong proliferation inhibition activity against various tested cancer cells with high selectivity to tumour and normal cells. BEL-7404 cells were found most sensitive to complex 2 by inducing apoptosis. The process involved the mitochondrial membrane potential depolarization, PARP-proteins cleavage, Bcl-2, p53, p21 expression and caspase family members' activation. Taking these findings into account, it can propose that complex 2 induce cancer cell apoptosis via mitochondrial pathways. The interaction of complex 2 with DNA investigated by fluorescence, CD and viscosity indicated that complex 2 interact with DNA mainly via intercalation., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A series of hybrids of scopoletin and substituted cinnamic acid were designed, synthesized and evaluated in vitro and in vivo against five human tumor cell lines [MCF-7, MDA-MB-231, A549, HCT-116, and HeLa] with doxorubicin as the positive control. Compounds 17a, 17b, 17c and 17g exhibited potent cytotoxic activity. Especially, compound 17b displayed broad spectrum activity with IC50 values ranging from 0.249 μM to 0.684 μM. Moreover, in a preliminary pharmacological study, 17b not only remarkably induced cellular apoptosis, but also clearly induced A549 cells cycle arrest at S phase. In vivo study showed that 17b significantly suppressed tumor growth in a dose-dependent manner without causing the loss of the mean body weight of mice, which was superior to doxorubicin. These preliminary results indicate that 17b is an optimal anti-cancer leading compound and merit further structural modification., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

[Pt(Q)2] (1) and [Pt(MQ)2] (2) exhibited enhanced cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702 cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively. While pifithrin-α, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1, 2 and pifithrin-α caused serious inhibition on p53, 1 and 2 significantly cause the loss of mitochondrial membrane potential and increase of the reactive oxygen species level, cytochrome c, apaf-1 and caspase-3/9 ratio in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial dysfunction pathway whereas pifithrin-α does not. The interactions of 1 and 2 with DNA are most probably via an intercalation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A new platinum(II) complex of [Pt(II)(L) (pn)]Cl·2H2O (1) (pn = 1,3-propanediamine) with 2-(4-methoxy-phenyl)imidazo [4,5-f]-[1,10]phenanthrolin (H-L) was synthesized and characterized. In complex 1, the platinum adopts a four-coordinated square planar geometry. Complex 1 exhibited selective cytotoxicity against NCI-H460, BEL-7402, SK-OV-3, SK-OV-3/DDP and HeLa cell lines with IC50 values in the micromolar range (9.7-35.8 μM), but low cytotoxicity toward normal human liver HL-7702 cells. Complex 1 caused HeLa cell cycle arrest at S phase and it induced HeLa apoptosis by the activation of caspase-3/9. Various experiments showed that complex 1 preferred to bind with G-quadruplex in c-myc. Taken together, we found that complex 1 exerted its antitumor activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and activation of caspase-3/9., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

[Zn₂(ClQ)₄(CH₃OH)₂] (1), [Zn(BrQ)₂(H₂O)₂] (2), [Zn₂(ClIQ)₄] (3) and [Cu(BrQ)₂] (4) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, and H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) were synthesized. Compounds 1-4 showed high anti-proliferative cytotoxicities against BEL-7404, SK-OV-3, NCI-H460 tumor cells, and HL-7702 normal cells in vitro, with IC₅₀ values in the 1.4 nM to 32.13 μM range. Compounds 2-4 exhibited significantly enhanced cytotoxicity against BEL-7404 cell line, comparing with free 5,7-dihalo-8-quinolinol. Western blotting analysis showed that 2, 3 depleted mutant p53 protein in MDA-MB-231, and compound 2 decreased the ratio of Bcl-2/Bax in NCI-H460 significantly. The binding abilities of 1-4 to DNA were stronger than that of free quinolinol ligand. Intercalation is the probable binding mode for the complexes and free quinolinol ligands with DNA., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Three cerium complexes: [Ce(ClQ)4] (1) (H-ClQ=5,7-dichloro-8-hydroxylquinoline), [Ce(ClIQ)4]·CH2Cl2·0.5H2O (2) (H-ClIQ=5-chloro-7-iodo-8-hydroxylquinoline) and [Ce2(BrQ)4(H-BrQ)(H2O)3Cl2]·1.5H2O (3) (H-BrQ=5,7-dibromo-8-hydroxylquinoline) were synthesized. The structures of 1 and 2 are mononuclear whereas 3 has a binuclear structure. Compared with the H-ClQ, H-ClIQ and H-BrQ, complexes 1-3 exhibited significantly higher cytotoxicity (IC50=0.09-5.23 μM) to SK-OV-3 and BEL-7404, 1 and 2 exhibited higher cytotoxicity to NCI-H460. Most the complexes and ligands exhibited higher cytotoxicity than cisplatin. Complexes 1-3 are much more sensitive to SK-OV-3 than to human normal liver cell HL-7702. Their antitumor activities were achieved through cell apoptosis and arrest at G0/G1-phase. Studies on the binding properties of 1-3 to DNA indicate that intercalation is the most probable binding mode., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

New platinum(II) complexes containing aminophosphonate ester were synthesized and fully characterized, which were found to possess better solubility in both organic solvents and water than cisplatin. These platinum(II) complexes exhibited considerable cytotoxicity against tumor cells MG-63, SK-OV-3, HepG2, BEL-7404 and low cytotoxicity to normal human liver cells HL-7702. Their antitumor activities were achieved through the induction of cell apoptosis and the cell cycle arrest at G1 phase. The electrophoretic mobility studies and CD spectral analysis revealed that the binding mode of complex 6 to DNA might be different from that of cisplatin., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Three tin(IV) complexes [Sn(ClQ)2Cl2] (1), [Sn(BrQ)2Cl2] (2) and [Sn(ClIQ)2Cl2] (3) were prepared (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) and their in vitro cytotoxicities against BEL7404, SKOV-3, NCI-H460, HL-7702 cell lines were evaluated. The complexes showed high anti-proliferative activity toward the tested cell lines with IC50 values ranging from 20 nM to 5.11 μM. Compared with 5,7-dihalo-8-quinolinol, most complexes exhibited significantly enhanced cytotoxicity (except 2 against SKOV-3 and NCI-H460). They also displayed some selective cytotoxicity favoring the tested tumor cells over the normal human liver HL-7702 cells. Compared with their quinolinol ligands, complexes 1-3 bind more strongly with DNA. Intercalation is the most probable binding mode for both the complexes and their quinolinol ligands., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Four isostructural lanthanide complexes with 5,7-dichloro-8-quinolinoline (H-ClQ): [Sm(ClQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (1), [Eu(ClQ)(3)(H(2)O)(2)]·0.5EtOH, (2), [Tb(ClQ)(3)(H(2)O)(2)]·0.5EtOH (3) and [Ho(ClQ)(3)(H(2)O)(2)]·H(2)O (4) were synthesized, in which the lanthanide was coordinated by three ClQ(-) anions and two aqua ligands. The in vitro cytotoxicities of complexes 1-4 against five human tumor cells were evaluated. The IC(50) values of complexes 1-4 against BEL7404, HeLa and A549 were in the range 1.2-6.3, 3.5-6.6 and 10.8-25.2 μM, respectively; except for complex 3 toward BEL7404, they all exhibited enhanced cytotoxicity in comparison to H-ClQ. The binding properties of complexes 1-4 to DNA examined by various methods indicated that complexes 1-4 interacted with DNA more strongly than free quinolinoline, and intercalation was the most probable binding mode for both the complexes and quinolinoline., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC₅₀ values ranging from 0.31 to 30.76 μM. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A series of novel 2',3'-diethanethio-2',3',5'-trideoxy-5'-triazoloribonucleosides was synthesized in excellent yields and their antitumor activity was evaluated. These nucleoside analogues with aromatic substituted triazole rings showed significantly improved activity towards a broad range of tumor cell lines and those without arene substitutes were inactive., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Abstract: Six new platinum(II) complexes with mono-aminophosphonate ester were synthesized and characterized by elemental analysis, 1H NMR, ESI-MS as well as single crystal X-ray diffraction analysis. They are mononuclear structures. In all the crystal structures of complexes 1–6, the platinum centre adopts an approximately square-planar geometry, which were found to possess excellent solubility in both organic solvents and water and exhibit considerable cytotoxicity against MG-63, SK-OV-3 and HepG2 cell lines, but low cytotoxicity towards normal human liver cell HL-7702. In contrast to cisplatin, their antitumour activities are achieved through the induction of cell apoptosis by G1 cell-cycle arrest. [Copyright &y& Elsevier]

There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl 3 ] ( 1 ), [Ir(2-MeO-Phtpy)Cl 3 ] ( 2 ) and [Ir(4-MeO-Phtpy)Cl 3 ] ( 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 50 values of 3.19–27.77 μ M against four cancer cell lines (BEL-7404, Hep-G2, NCI-H460 and MGC80-3 cells). Cellular mechanism studies suggested that complexes 1 – 3 directly targeted c-myc promoter elements and inhibited the telomerase activity. In addition, complexes 1 – 3 may trigger cell apoptosis via a mitochondrial dysfunction pathway. We postulated that the difference in the in vitro antitumor activities of complexes 1 – 3 is mainly dependent on the position of the methoxy group on the phenyl ring of the iridium ligand. [ABSTRACT FROM AUTHOR]

Two G-quadruplex ligands: [Co( H-L a ) 2 Cl 2 ] ( Co1 ) and [Co( L b ) 2 ][CoCl 4 ]⋅2H 2 O ( Co2 ) have been synthesized and characterized. Two cobalt oxoisoaporphine complexes exhibited selective cytotoxicity to SK-OV-3/DDP cells than for HL-7702 cells. Cytotoxic mechanism studies indicated that both Co1 and Co2 were telomerase inhibitor targeting c-myc, telomere, and bcl-2 G4s, and triggering cell senescence and apoptosis, which caused S phase arrest. They also induced mitochondrial dysfunction. The better antitumor activity of Co2 , which should be correlated with a moiety of 2-[5-(2-pyridinyl)-1 H -pyrrol-2-yl]pyridine in the L b . Importantly, Co2 at high doses showed at least the same level of tumor growth inhibition efficacy compared to that of cisplatin, and better in vivo safety profile. [ABSTRACT FROM AUTHOR]