Mangiferin is a new potential antimalarial and anticancer drug for targeting serine hydroxymethyltransferase.

Mangiferin, a polyphenolic xanthone glycoside found in various botanical sources, including mango (Mangifera indica L.) leaves, can exhibit a variety of bioactivities. Although mangiferin has been reported to inhibit many targets, none of the studies have investigated the inhibition of serine hydroxymethyltransferase (SHMT), an attractive target for antimalarial and anticancer drugs. SHMT, one of the key enzymes in the deoxythymidylate synthesis cycle, catalyzes the reversible conversion of l-serine and (6S)-tetrahydrofolate (THF) into glycine and 5,10-methylene THF. Here, in vitro and in silico studies were used to probe how mangiferin isolated from mango leaves inhibits Plasmodium falciparum and human cytosolic SHMTs. The inhibition kinetics at pH 7.5 revealed that mangiferin is a competitive inhibitor against THF for enzymes from both organisms. Molecular docking and molecular dynamic (MD) simulations demonstrated the inhibitory effects of the deprotonated forms of mangiferin, specifically the C6-O- species and its resonance C9-O- species appearing at pH 7.5, combined with two docked poses, either a xanthone or glucose moiety, placed inside the THF-binding pocket. The MD analysis revealed that both C6-O- and its resonance-stabilized C9-O- species can favorably bind to SHMT in a similar fashion to THF, supporting the THF competitive inhibition of mangiferin. In addition, characterization of the proton dissociation equilibria of isolated mangiferin revealed that only three hydroxy groups of the xanthone moiety, C6-OH, C3-OH, and C7-OH, underwent varying degrees of deprotonation with pKa values of 6.38 ± 0.11, 8.21 ± 0.35, and 12.37 ± 0.30, respectively, while C1-OH remained protonated. Altogether, our findings demonstrate a new bioactivity of mangiferin and provide the basis for the future development of mangiferin as a potent antimalarial and anticancer drug.

Diaqua-{2,6-bis-[N-(2-pyridinylmeth-yl)-carbamo-yl]-phenolato-κO,O}zinc(II).

In the title compound, [Zn(C(20)H(17)N(4)O(3))(2)(H(2)O)(2)], the Zn(II) atom, lying on a twofold rotation axis, is six-coordinated in a distorted octa-hedral geometry by two phenolate O atoms and two carbonyl O atoms from two 2,6-bis-[(pyridin-2-ylmeth-yl)-carbamo-yl]phenolate ligands and by two water mol-ecules. A three-dimensional network is built up from an extensive array of hydrogen bonds and π-π inter-actions between the pyridyl rings, with a centroid-centroid distance of 3.666 (3) Å.

Erratum: Diaqua-{2,6-bis-[N-(2-pyridinylmeth-yl)-carbamo-yl]-phenolato-κO,O}zinc(II). Corrigendum.

The chemical name in the title of the paper by Suksai, Watchasit, Tuntulani & Pakawatchai [Acta Cryst. (2008), E64, m884-m885] is corrected.[This corrects the article DOI: 10.1107/S1600536808016693.].

Tuning the reactivity of copper complexes supported by tridentate ligands leading to two-electron reduction of dioxygen.

A series of copper complexes bearing polypyridyl tridentate ligands have been prepared to fine tune their reactivity toward the oxygen reduction reaction (ORR). During the process of preparation of our copper complexes, we successfully obtained two new crystal structures which are [Cu2(µ-Cl)2(adpa)2](ClO4)2 (2b) and [Cu2(addpa)(CH3CN)2(ClO4)2](ClO4)2 (3a) and a new structure [Cu2(addpa)(CH3CN)2(H2O)2](ClO4)4 (3b) captured after the catalytic ORR. Electrochemical studies and stoichiometric chemical reduction of copper(ii) complexes by ascorbic acid indicated that the presence of an anthracene unit helps to facilitate the reduction of Cu(ii) as well as the stabilisation of Cu(i) species. Regarding oxygen activation, the dinuclear Cu(i) complex 3a showed significantly higher ORR activity than its analogous mononuclear complex 2a. Complex 3a was also found to be relatively robust and competent in catalytic O2 reduction. The observed H2O2 product after this catalysis, together with the data obtained from DFT calculations supported that 3a exhibited a 2H+, 2e- catalytic activity towards the ORR as opposed to the expected 4H+, 4e- process usually found in copper complexes with tridentate ligands. The proton (H+) source for this process was expected from ascorbic acid which also serves as a reducing agent in this reaction. This work highlighted an approach for tuning the ORR activity of the copper complexes by the introduction of a conjugated-π moiety to the supporting ligand.

Discriminate sensing of pyrophosphate using a new tripodal tetramine-based dinuclear Zn(II) complex under an indicator displacement assay approach.

In this research, the dinuclear Zn(ii) complex of anthracene based tripodal tetramine Zn2L was synthesized, and its sensing abilities towards anions was investigated using the indicator displacement assay (IDA) approach with four complexometric indicators: pyrocatechol violet (PV), bromopyrogallol red (BPG), methylthymol blue (MTB) and xylenol orange (XO). UV-vis spectrophotometry results indicated that the Zn2L-MTB ensemble sensor could discriminate the pyrophosphate anion (PPi) from other phosphate containing anions. (1)H and (31)P NMR spectroscopy as well as DFT calculations confirmed that PPi bound to Zn2L in a 2 : 2 manner. Both NMR spectroscopy and UV-vis spectrophotometry suggested that the two bulky tripodal tetramine units in Zn2L played an important role to provide the ensemble cleft for MTB, giving rise to an ensemble that could be displaced exclusively by PPi. The detection limit of PPi for the reported IDA system was 0.3 µM in 20% (v/v) water-acetonitrile buffered at pH 7.4 with HEPES.

New calix[4]arene derivatives as ionophores in polymeric membrane electrodes for Ag(I): comparative selectivity studies and detection of DNA hybridization.

Four calix[4]arene derivatives containing various donor atoms and different topology (L1-L4) have been synthesized and used as neutral ionophores to fabricate silver ion selective electrodes (Ag-ISEs) which were characterized in terms of their potentiometric selectivities and complex formation constants. The ionophore L2 having two nitrogen and two sulfur donors showed stronger interactions with Ag(+) and the highest selectivity coefficient towards Ag(+). The best membrane electrode was prepared from L2 and used to fabricate silver ion selective microelectrodes (Ag-ISµEs) which could detect silver ions in 1000 µL samples with detection limit around 1 µM using sodium ion microelectrodes as a pseudo reference electrode. Such potentiometric measurement was then applied to detect DNA hybridization on a gold substrate, employing immobilized lipoic acid-modified pyrrolidinyl PNA (Lip-acpcPNA) as a probe. The hybridization between the neutral Lip-acpcPNA probe and DNA target led to a negatively charged surface that could bind positively charged silver nanoparticles (AgNPs(+)) via electrostatic interactions. The hybridization signal was observed by dissolution of the electrostatically adsorbed AgNPs(+) with hydrogen peroxide. Excellent discrimination of complementary from single mismatched and non-complementary DNA targets was achieved under non-stringent conditions. The detection limit of DNA was 0.2 µM in 1000 µL samples.

New polymeric membrane cadmium(II)-selective electrodes using tripodal amine based ionophores.

Fabrication of PVC membrane electrodes incorporating selective neutral carriers for Cd(2+) was reported. The ionophores were designed to have different topologies, donor atoms and lipophilicity by attaching tripodal amine (TPA) units to the lipophilic anthracene (ionophore I) and p-tert-butylcalix[4]arene (ionophores II, III and IV). The synthesized ionophores were incorporated to the plasticized PVC membranes to prepare Cd(II) ion selective electrodes (ISEs). The membrane electrodes were optimized by changing types and amounts of ionic sites and plasticizers. The selectivity of the membranes fabricated from the synthesized ionophores was evaluated, the relationship between structures of ionophores and membrane characteristics were explored. The ionophore IV which composed of two opposites TPA units on the calix[4]arene compartment showed the best selectivity toward Cd(2+). The best membrane electrode was fabricated from ionophore IV (10.2 mmol kg(-1)) with KTpClPB (50.1 mol% related to the ionophore) as an ion exchanger incorporated in the DOS plasticized PVC membrane (1:2; PVC:DOS). The Cd-ISE fabricated from ionophore IV exhibited good properties with a Nernstian response of 29.4±0.6 mV decade(-1) of activity for Cd(2+) ions and a working concentration range of 1.6×10(-6)-1.0×10(-2)M. The sensor has a fast response time of 10s and can be used for at least 1 week without any divergence in potential. The electrode can be used in the pH range of 6.0-9.0. The proposed electrodes using ionophores III and IV were employed as a probe for determining Cd(2+) from the oxidation of CdS QDs solution and the real treatment waste water sample with excellent results.