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Graphdiyne (GDY), which is an sp- and sp2-hybridized 2D graphene-like material, shows an abundant fully π-conjugated system and excellent conductivity. In addition, water-soluble pillar[5]arene (WP5) displays outstanding host–guest recognition properties. Therefore, the electrochemical sensing system of WP5–GDY, constructed via strong π–π stacking between WP5 and GDY, shows prominent conductivity and a supramolecular recognition ability. Hence, the ultrasensitive and robust electrochemical determination of methylamphetamine (MA) was developed using the novel composite of WP5–GDY for the first time. For MA detection, the electrochemical sensor showed a linear response range of 0.05–30.0 μM and a detection limit of 0.016 μM (S/N = 3). The host–guest mechanism between WP5 and MA was studied via binding constant (Ka) measurements, molecular docking, and 1H NMR analysis. The developed electrochemical sensing platform was also successfully used to detect MA in human urine samples, which confirms its potential applications in the detection of drugs of abuse, illicit drugs and misused prescriptions, which will protect public health, social stability and global security. [ABSTRACT FROM AUTHOR]

A binuclear Schiff base copper(II) complex [Cu2(L-H)2]Cl2 (1, L = N-(2-hydroxylbenzylidene)-benzo[d]imidazol-2-amine) was synthesized and characterized by elemental analysis, ESI-MS, HRMS, IR, and molar conductivity. Magnetization measurements revealed that 1 showed the usual, moderate-to-strong intramolecular antiferromagnetically coupling exchange interaction between two copper(II) centers. The electrochemical behaviour in DMF showed that 1 has followed quasi-irreversible nature with two successive one-electron reductions as follows: CuIICuII ⇔ CuIICuI ⇔ CuICuI. Complex 1 could bind to DNA by the groove binding mode and electrostatic interaction and induce a conformational variation in DNA. Additionally, 1 could efficiently cleave the supercoiled plasmid DNA into its nicked and linear forms by the oxidative mechanism. The cell experiments showed that 1 could effectively enter cancer cells, even the nucleus, induce cellular apoptosis, and exhibit cytotoxicity comparable to that of cisplatin against HeLa and A549 cell lines; it also has a more potent cytotoxicity against MCF-7 cell lines. [ABSTRACT FROM AUTHOR]

Polynuclear platinum(II) complexes represent a class of great prospective Pt-based antitumor drugs that may expand the antitumor spectrum and overcome the clinical problems of drug resistance and side effects of platinum-based drugs. Herein, a novel star-shaped trinuclear platinum(II) complex [Pt3(L–3H)Cl3] (1, L = 2,4,6-tris[(2-hydroxybenzyl)(2-pyridylmethyl)amine]-1,3,5-triazine) and its monomer [Pt(L′–H)Cl] (2, L′ = (2-hydroxybenzyl)(2-pyridylmethyl)amine) were synthesized and characterized. The in vitro antiproliferative activities of complexes 1 and 2 against a panel of human cancer cell lines including MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast), HepG-2 (liver), and A549 (lung) were investigated. The results revealed that 1 exhibited much higher antiproliferative properties than its monomer 2 against the tested cell lines. Importantly, 1 possessed 3.3-fold higher antiproliferative activity as compared with cisplatin against the TNBC cell line MDA-MB-231. Another TNBC cell line MDA-MB-468 is also sensitive to 1. The results indicated that 1 might have the potential to act as a candidate for the treatment of TNBC. Cellular uptake and distribution studies showed that 1 could pass through the membrane of cells and enter into cells and mainly accumulate in the nuclei and mitochondria. 1 could bind to DNA in a cooperative groove-electrostatic-platinating binding mode and induce stronger DNA double-strand breaks (DSBs) and damaging effects on MDA-MB-231 than cisplatin (upregulation of γ-H2AX). Moreover, the DNA damage could not be easily repaired (upregulation of p53), which would exert a much positive influence on the overcoming of drug resistance. Additionally, flow cytometry studies showed that 1 arrested the cell cycle in the G0/G1 phase, induced mitochondrial membrane depolarization, increased ROS generation, and induced cell apoptosis. The results demonstrated that 1 could target simultaneously mitochondria and nuclei that gave rise to mitochondrial injury and DNA damage and ultimately efficiently promote the apoptotic death of tumor cells. Further mechanistic studies showed that 1 induced MDA-MB-231 cell apoptosis via the p53-mediated mitochondrial pathway by upregulating Bax and cytochrome c and downregulating Bcl-2 proteins, leading to the activation of caspase-3 and upregulation of the cleaved-PARP level. Taken together, 1 with such a synergic mechanism has great potential to be an effective anticancer agent that can overcome treatment resistance in TNBC. [ABSTRACT FROM AUTHOR]

Polynuclear platinum(II) complexes represent a class of great prospective Pt-based antitumor drugs that may expand the antitumor spectrum and overcome the clinical problems of drug resistance and side effects of platinum-based drugs. Herein, a novel star-shaped trinuclear platinum(II) complex [Pt 3 (L-3H)Cl 3 ] (1, L = 2,4,6-tris[(2-hydroxybenzyl)(2-pyridylmethyl)amine]-1,3,5-triazine) and its monomer [Pt(L'-H)Cl] (2, L' = (2-hydroxybenzyl)(2-pyridylmethyl)amine) were synthesized and characterized. The in vitro antiproliferative activities of complexes 1 and 2 against a panel of human cancer cell lines including MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast), HepG-2 (liver), and A549 (lung) were investigated. The results revealed that 1 exhibited much higher antiproliferative properties than its monomer 2 against the tested cell lines. Importantly, 1 possessed 3.3-fold higher antiproliferative activity as compared with cisplatin against the TNBC cell line MDA-MB-231. Another TNBC cell line MDA-MB-468 is also sensitive to 1. The results indicated that 1 might have the potential to act as a candidate for the treatment of TNBC. Cellular uptake and distribution studies showed that 1 could pass through the membrane of cells and enter into cells and mainly accumulate in the nuclei and mitochondria. 1 could bind to DNA in a cooperative groove-electrostatic-platinating binding mode and induce stronger DNA double-strand breaks (DSBs) and damaging effects on MDA-MB-231 than cisplatin (upregulation of γ-H2AX). Moreover, the DNA damage could not be easily repaired (upregulation of p53), which would exert a much positive influence on the overcoming of drug resistance. Additionally, flow cytometry studies showed that 1 arrested the cell cycle in the G0/G1 phase, induced mitochondrial membrane depolarization, increased ROS generation, and induced cell apoptosis. The results demonstrated that 1 could target simultaneously mitochondria and nuclei that gave rise to mitochondrial injury and DNA damage and ultimately efficiently promote the apoptotic death of tumor cells. Further mechanistic studies showed that 1 induced MDA-MB-231 cell apoptosis via the p53-mediated mitochondrial pathway by upregulating Bax and cytochrome c and downregulating Bcl-2 proteins, leading to the activation of caspase-3 and upregulation of the cleaved-PARP level. Taken together, 1 with such a synergic mechanism has great potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.