•We investigate the biological activity of three new ternary copper(II) complexes.•Chelated by phenanthroline, the anti-cancer activity of the drugs increases a lot.•Drug 3 shows more significant cytotoxic activities than 1 and 2.•All the complexes can cause DNA damage.Three mononuclear mixed ligand Cu(II) complexes of the type [Cu(L)(DTHA)]H2O⋅CH3OH, where H2DTHA is 2-(3,5-di-tert-butyl-2-hydroxybenzylamino) acetic acid and the co-ligand L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2) dipyrido [3,2-a:2′,3′-c]phenazine (dppz, 3) have been isolated and characterized. Absorption and emission spectral studies and viscosity measurements indicated that 3 interacts with DNA more strongly than all of the other complexes through intercalation mode. Furthermore, cytotoxicity studies on the tested four cell line indicated that they can efficiently inhibit the cell proliferation in a time-dependent manner, and the Hoechst 33258 staining assays have also been employed in finding the extent of DNA damage.Three new ternary copper(II) complexes 1–3 are synthesized and characterized. All of them show significant cytotoxic, cell apoptosis and DNA-biding activities.

Three new ternary copper(II) complexes, [Cu2(phen)2(PDIMAla)(H2O)2](ClO4)2·CH3OH (1), [Cu2(dpq)2(PDIMAla)(H2O)2](ClO4)2·CH3OH (2) and [Cu2(dppq)2(PDIMAla)(H2O)2](ClO4)2·CH3OH (3) (phen = 1,10-phenanthroline, dpq = dipyrido[3,2:2′,3′-f]quinoxaline, dppz = dipyrido[3,2-a:2′,3′-c]phenazine, H2PDIMAla = N,N′-(p-xylylene)di-alanine acid) have been synthesized and the complex 1 has been structurally characterized by single-crystal X-ray crystallography, spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis and viscosity measurements. The results indicate that the three compounds, especially the complex 3, can strongly bind to calf-thymus DNA (CT–DNA). The intrinsic binding constants Kb of the ternary copper(II) complexes with CT–DNA are 0.38 × 105, 1.4 × 105 and 7.8 × 105 for 1, 2 and 3, respectively. Comparative cytotoxic activities of the copper(II) complexes are also determined by acid phosphatase assay. The results show that the ternary copper(II) complexes have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60) and human prostate (PC3) cell lines. Investigation of antioxidation property show that all the copper(II) complexes have strong scavenging effects for hydroxyl radicals.Graphical abstractThree novel ternary copper(II) complexes 1–3 are synthesized and characterized. All of them show significant cytotoxic, antioxidation and DNA-biding activities.Highlights► We investigate the biological activity of three new ternary copper(II) complexes. ► Chelated by phenanthroline, the anti-cancer activity of the drugs increase a lot. ► Drug 3 show more significant cytotoxic activities than 1 and 2.

Of all the causes identified for the disease hyper-immunoglobulinemia E syndrome (HIES), a homozygous mutation in tyrosine kinase2 (TYK2) and heterozygous mutations in STAT3 are implicated the defects in Jak/STAT signalling pathway in the pathogenesis of HIES. Mutations of STAT3 have been frequently clinically identified in autosomal-dominant (AD) HIES patients’ cells, and therefore, the genotype of STAT3 has been associated with the phenotype of HIES. Here, we conducted studies on the functional loss of the seven specific STAT3 mutations correlated with AD-HIES. Using STAT3-null human colon carcinoma cell line A4 cells, we generated seven mutants of STAT3 bearing single mutations clinically identified in AD-HIES patients’ cells and studied the functional loss of these mutants in IL-6-Jak/STAT3 signalling pathway. Our results show that five STAT3 mutants bearing mutations in the DNA-binding domain maintain the phosphorylation of Tyr705 and the ability of dimerization while the other two with mutations in SH2 domain are devoid of the phosphorylation of Try705 and abrogate the dimerization in response to IL-6. The phosphorylation of Ser727 in these mutants shows diversity in response to IL-6. These mutations eventually converge on the abnormalities of the IL-6/Gp130/Jak2-mediated STAT3 transactivation on target genes, indicative of the dysregulation of JAK/STAT signalling present in HIES.

Ferrocene compounds are a class of biologically active compounds that has antitumour and antifungal properties. This study investigated the induction of apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6-ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We found that FTFs could suppress the viability of HT1080 cells. Cell cycle analysis showed that proliferative inhibition of HT1080 cells occurred through apoptosis, as the cells were blocked in G1 phase. Moreover, mitochondrial membrane staining assay demonstrated that FTFs exposure significantly decreased mitochondrial membrane potential. Finally, under the stress of FTFs, Bax/Bcl-2 ratio in HT1080 cells was significantly increased. These results suggested that FTFs-induced apoptosis in HT1080 cells may work dependent on a Bax/Bcl-2 pathway.The cyclization of 4-amino-5-substituted 1,2,4-triazol-3-thione with α-halogenocarbonyl compounds has been the most useful method for the formation of the 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine ring system. Highlights► Thiadiazine derivatives could suppress the viability of HT1080 cells. ► Proliferative inhibition of HT1080 cells occurred through apoptosis. ► Thiadiazine derivatives exposure decreased mitochondrial membrane potential. ► Bax/Bcl-2 ratio in cells was increased under the stress of Thiadiazine derivatives.

In this work, glycopolypeptide nanoparticles (GPNPs) composed of Mn doped ZnS quantum dots (QDs) as core and glycopolypeptides as shell were synthesized through the surface initiated polymerization of N-carboxyanhydrides and surface condensation polymerization with carboxymethyldextran on amine-functionalized QDs. The loading and release behavior of ibuprofen on the GPNPs were investigated. The GPNPs exhibited not only high loading but also controlled release behavior. The cytotoxicity of the GPNPs was evaluated by incubating with HEK293T cell lines and they were shown to be of low cytotoxicity. They appear to be a very promising candidate for targeted drug delivery.Graphical abstractHighlights• Multifunctional core–shell structured glycopolypeptide nanoparticles were fabricated by NCA chemistry. • Glycopolypeptides shell was dextran-poly(l-alanine) and could offer rich –OH and –NH2 for combining drug by multi-bond effect. • Glycopolypeptide nanoparticles are a low-cytotoxic material.

Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour, antifungal, antibacterial, antioxidant and antivenom properties. We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS) isolated from Cremanthodium discoideum (C. discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells. Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover, HOBS was able to increase tyrosine-α-ketoglutarate transaminase activity, decrease α foetoprotein level and γ-glutamyl transferase activity. In addition, we found that HOBS inhibited the anchorageindependent growth of SMMC-7721 cells in a dose-dependent manner. Taken together, all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.