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The success of platinum-based chemotherapeutic drugs for clinical cancer treatments has inspired tremendous research efforts on developing new metallic anticancer agents with improved cytotoxic activity and reduced side effects. 2,2′;6′,2″-Terpyridine and its 4′-substituted derivatives have showed great potential as ligand compartments for designing new anticancer drug candidates involving base metals. In this work, we synthesized a series of cobalt and iron coordination compounds based on 4′-pyridyl-2,2′;6′,2″-terpyridine, including homoleptic complexes, a dinuclear bridged complex and 1- and 2-dimensional coordination polymers/networks. The polymorphism of two homoleptic CoII and FeII complexes has been described along with the structural characterization of a CoII coordination polymer and dinuclear FeIII complex by X-ray crystallography. These compounds were tested preliminarily as precatalysts for the regioselective hydrosilylation of styrene. Their cytotoxic activities against two human breast cancer cell lines (MCF-7 and MDA-MB 468) and a normal breast epithelial cell line (MCF-10A) were investigated in order to observe the best-performing drug candidates. [ABSTRACT FROM AUTHOR]

Chilli pepper is one of the most important and widely cultivated pepper types in China. It has high nutritional and economic value. Capsicum frutescens L. is one of the chilli pepper types in production. In October 2022, a new disease showing blight of the entire chilli pepper plant was observed in Nanchang City, Jiangxi Province. The fungal isolates consistently obtained from the diseased samples were identified as Diaporthe caryae C. M. Tian & Qin Yang based on morphological characteristics, pathogenicity test and phylogenetic analysis of four genes, including internal transcribed spacer region (rDNA‐ITS), translation elongation factor 1‐alpha gene (TEF1), beta‐tubulin gene (TUB2), and calmodulin (CAL). Although other Diaporthe species have been reported as pathogens of peppers previously, to our knowledge, this is the first report of D. caryae causing stem blight of pepper in the world. D. caryae was reported to be able to infect various fruit trees such as kiwifruit, peach, pear, and pecan, resulting in kiwifruit rot, peach constriction canker, pear shoot canker, and pecan dieback, respectively. The host range of D. caryae has expanded from fruit trees to vegetable crops. [ABSTRACT FROM AUTHOR]

Introduction Parkinson disease is the second most common neurodegenerative disorder after Alzheimer disease and affects approximately 1% of the population over 50 years of age. Although most cases of Parkinson [...], Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.L368Q and p.P395L) in both families. Functional studies demonstrated that both mutations were loss-of-function mutations that severely reduced levels of mature (85-kDa) DAT while having a differential effect on the apparent binding affinity of dopamine. Thus, in humans, loss-of-function SLC6A3 mutations that impair DAT-mediated dopamine transport activity are associated with an early-onset complex movement disorder. Identification of the molecular basis of IPD suggests SLC6A3 as a candidate susceptibility gene for other movement disorders associated with parkinsonism and/or dystonic features.

Mitomycin C (MC), an antitumor drug, and decarbamoylmitomycin C (DMC), a derivative of MC, alkylate DNA and form deoxyguanosine monoadducts and interstrand crosslinks (ICLs). Interestingly, in mammalian culture cells, MC forms primarily deoxyguanosine adducts with a 1"-R stereochemistry at the guanine-mitosene bond (1"-α) whereas DMC forms mainly adducts with a 1"-S stereochemistry (1"-β). The molecular basis for the stereochemical configuration exhibited by DMC has been investigated using biomimetic synthesis. Here, we present the results of our studies on the monoalkylation of DNA by DMC. We show that the formation of 1"-β-deoxyguanosine adducts requires bifunctional reductive activation of DMC, and that monofunctional activation only produces 1"-α-adducts. The stereochemistry of the deoxyguanosine adducts formed is also dependent on the regioselectivity of DNA alkylation and on the overall DNA CG content. Additionally, we found that temperature plays a determinant role in the regioselectivity of duplex DNA alkylation by mitomycins: At 0 °C, both deoxyadenosine (dA) and deoxyguanosine (dG) alkylation occur whereas at 37 °C, mitomycins alkylate dG preferentially. The new reaction protocols developed in our laboratory to investigate DMC-DNA alkylation raise the possibility that oligonucleotides containing DMC 1"-β-deoxyguanosine adducts at a specific site may be synthesized by a biomimetic approach., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mitomycin C (MC) is an anticancer agent that alkylates DNA to form monoadducts and interstrand cross-links. Decarbamoylmitomycin C (DMC) is an analogue of MC lacking the carbamate on C10. The major DNA adducts isolated from treatment of culture cells with MC and DMC are N 2 -deoxyguanosine (dG) adducts and adopt an opposite stereochemical configuration at the dG-mitosene bond. To elucidate the molecular mechanisms of DMC-DNA alkylation, we have reacted short oligonucleotides, calf thymus, and M. luteus DNA with DMC using biomimetic conditions. These experiments revealed that DMC is able to form two stereoisomeric deoxyadenosine (dA) adducts with DNA under bifuntional reduction conditions and at low temperature. The dA-DMC adducts formed were detected and quantified by HPLC analysis after enzymatic digestion of the alkylated DNA substrates. Results revealed the following rules for DMC dA alkylation: (i) DMC dA adducts are formed at a 48- to 4-fold lower frequency than dG adducts, (ii) the 5'-phosphodiester linkage of the dA adducts is resistant to snake venom diesterase, (iii) end-chain dA residues are more reactive than internal ones in duplex DNA, and (iv) nucleophilic addition by dA occurs on both faces of DMC and the ratio of stereoisomeric dA adducts formed is dependent on the end bases located at the 3' or 5' position. A key finding was to discover that temperature plays a determinant role in the regioselectivity of duplex DNA alkylation by DMC: at 0 °C, both dA and dG alkylation occur, whereas at 37 °C, DMC preferentially alkylates dG residues.