Bis(μ2-2-amino-5-nitro­benzoato)bis­(2-amino-5-nitro­benzoato)octa­butyldi-μ3-oxido-tetra­tin(IV)

In the title complex, [Sn4(C4H9)8(C7H5N2O4)4O2], all four SnIV atoms are five-coordinated with distorted trigonal–bipyramidal SnC2O3 geometries. Two SnIV atoms are coordin­ated by two butyl groups, one benzoate O atom and two bridging O atoms, whereas the other two SnIV atoms are coordinated by two butyl groups, two benzoate O atoms and a bridging O atom. All the butyl groups are equatorial with respect to the SnO3 trigonal plane. In the crystal, mol­ecules are linked into a two-dimensional layer parallel to the ab plane by inter­molecular N—H⋯O and C—H⋯O hydrogen bonds and further stabilized by a π–π inter­action [centroid–centroid distance = 3.6489 (11) Å]. Intra­molecular N—H⋯O and C—H⋯O hydrogen bonds stabilize the mol­ecular structure. Two of the butyl groups are each disordered over two sets of sites with site-occupancy ratios of 0.510 (4):0.490 (4) and 0.860 (5):0.140 (5)

Octa­butylbis[μ2-4-(diethyl­amino)­benzoato-κ2 O:O′]bis­[4-(diethyl­amino)­benzoato-κO]di-μ3-oxido-tetra­tin(IV)

The asymmetric unit of the title complex, [Sn4(C4H9)8(C11H14NO2)4O2], consists of two crystallographically independent half-mol­ecules. The other halves are generated by crystallographic inversion centers. In each tetra­nuclear mol­ecule, both of the two independent Sn atoms are five-coordinated, with distorted trigonal–bipyramidal SnC2O3 geometries. One Sn atom is coordinated by two butyl groups, one O atom of the benzoate anion and two bridging O atoms, whereas the other Sn atom is coordinated by two butyl groups, two O atoms of the benzoate anions and a bridging O atom. All the butyl groups are equatorial with respect to the SnO3 trigonal plane. Weak intra­molecular C—H⋯O hydrogen bonds stabilize the mol­ecular structures. In one mol­ecule, two of the butyl groups and the bridging benzoate anion are each disordered over two positions

(2-Amino-3-nitro­benzoato-κO)triphenyl­tin(IV)

The asymmetric unit of the title compound, [Sn(C6H5)3(C7H5N2O4)], consists of two independent mol­ecules. In each mol­ecule, the four-coordinated SnIV atom exists in a distorted tetra­hedral geometry and two intra­molecular N—H⋯O hydrogen bonds with S(6) ring motifs are present. In one mol­ecule, the benzene ring of the 2-amino-3-nitro­benzoate ligand makes dihedral angles of 42.74 (11), 89.66 (13) and 53.04 (10)° with the three phenyl rings. The corresponding dihedral angles for the other mol­ecule are 6.29 (11), 66.55 (11) and 62.33 (10)°. In the crystal, a weak inter­molecular C—H⋯π inter­action and a π–π stacking inter­action with a centroid–centroid distance of 3.5877 (12) Å are observed

(Methanol-κO)(2-methyl-3-nitro­benzoato-κO)triphenyl­tin(IV)

The five-coordinate Sn atom in the title compound, [Sn(C6H5)3(C8H6NO4)(CH3OH)], exists in a trans-C3SnO2 trigonal-bipyramidal coordination polyhedron of which the O atoms of the methanol mol­ecule and carboxyl­ate group occupy the apical sites. In the crystal, adjacent mol­ecules are linked by inter­molecular O—H⋯O inter­actions, generating a helical hydrogen-bonded chain running along the b axis

[3-(Dimethyl­amino)benzoato]triphenyl­tin(IV)

In the title compound, [Sn(C6H5)3(C9H10NO2)], the Sn atom is coordinated by three phenyl groups and a carboxyl­ate anion in a distorted tetra­hedral geometry. An intra­molecular C—H⋯O inter­action forms an S(7) ring motif. The dihedral angles between the benzoate group and the other three phenyl rings are 76.94 (8), 66.82 (8) and 42.34 (9)°. The crystal structure is further stabilized by inter­molecular C—H⋯π inter­actions

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

Background: Lactobacillus plantarum, a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum. Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated. Methods: Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses. Results: UL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis. Conclusion: In conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain

A population of >6 million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome-21-gene BACE2, but prevented by combined chemical β and γ-secretase inhibition. We found that T21-organoids secrete increased proportions of Aβ-preventing (Aβ1-19) and Aβ-degradation products (Aβ1-20 and Aβ1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1-inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided