Antitumor properties of Ganoderma lucidum polysaccharides and terpenoids

Ganoderma lucidum is an edible medicinal mushroom with immunomodulatory and antitumor properties, which are mainly attributed to polysaccharides and triterpenes that can be isolated from mycelia, fruiting bodies and spores. G. lucidum has been us d in a powdered form, as a medicinal beverage and a nutraceutical food (usually dried). In the present review we report some historical facts and the experimental evidence that polysaccharides and triterpenes obtained from this mushroom present potential antitumor activity. Direct effects on tumor cells include induction of apoptosis and interference in the cell cycle, whereas indirect effects are based on the modulation of immune response, usually impaired by cancer cells. Data indicate that G. lucidum can be used as a complementary tool for treatment of cancer patients. © by São Paulo State University.

Low molecular weight compounds from mushrooms as potential Bcl-2 inhibitors: docking and virtual screening studies

Mushrooms have the ability to promote apoptosis in tumor cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the ability to inhibit Bcl-2 is an ongoing research topic in drug discovery. In this study, we started by analyzing Bcl-2 experimental structures that are currently available in Protein Data Bank database. After analysis of the more relevant Bcl-2 structures, 4 were finally selected. An analysis of the best docking methodology was then performed using a cross-docking and re-docking approach while testing 2 docking softwares: AutoDock 4 and AutoDock Vina. Autodock4 provided the best docking results and was selected to perform a virtual screening study applied to a dataset of 40 Low Molecular Weight (LMW) compounds present in mushrooms, using the selected Bcl-2 structures as target. Results suggest that steroid are the more promising family, among the analyzed compounds, and may have the ability to interact with Bcl-2 and this way promoting tumor apoptosis. The steroids that presented lowest estimated binding energy (ΔG) were: Ganodermanondiol, Cerevisterol, Ganoderic Acid X and Lucidenic Lactone; with estimated ΔG values between -8,45 and -8,23 Kcal/mol. A detailed analysis of the docked conformation of these 4 top ranked LMW compounds was also performed and illustrates a plausible interaction between the 4 top raked steroids and Bcl-2, thus substantiating the accuracy of the predicted docked poses. Therefore, tumoral apoptosis promoted by mushroom might be related to Bcl-2 inhibition mediated by steroid family of compounds.

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.

8-Ammonionaphthalene-2-sulfonate monohydrate : the zwitterionic hydrate of 1,7-Cleve's acid

The structure of 8-amino-2-naphthalenesulfonic acid monohydrate (1,7-Cleve's acid hydrate), C10H9NO3S.H2O, shows the presence of a sulfonate-aminium group zwitterion, both groups and the water molecule of solvation giving cyclic R3/3(8) intermolecular hydrogen-bonding interactions forming chains which extend down a axis of the unit cell. Additional peripheral associations, including weak aromatic ring pi-pi interactions [centroid-centroid distance 3.6299(15)A], result in a two-dimensional sheet structure.

Zero- one- and two-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, nicotinamide and isonicotinamide

The structures of the anhydrous 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, 3-(aminocarboxy) pyridine (nicotinamide) and 4-(aminocarbonyl) pyridine (isonicotinamide), namely 2-aminopyrimidinium 2-carboxy-4,5-dichlorobenzoate C4H6N3+ C8H3Cl2O4- (I), 3-(aminocarbonyl) pyridinium 2-carboxy-4,5-dichlorobenzoate C6H7N2O+ C8H3Cl2O4- (II) and the unusual salt adduct 4-(aminocarbonyl) pyridinium 2-carboxy-4,5-dichlorobenzoate 2-carboxymethyl-4,5-dichlorobenzoic acid (1/1/1) C6H7N2O+ C8H3Cl2O4-.C9H6Cl2O4 (III) have been determined at 130 K. Compound (I) forms discrete centrosymmetric hydrogen-bonded cyclic bis(cation--anion) units having both R2/2(8) and R2/1(4) N-H...O interactions. In compound (II) the primary N-H...O linked cation--anion units are extended into a two-dimensional sheet structure via amide-carboxyl and amide-carbonyl N-H...O interactions. The structure of (III) reveals the presence of an unusual and unexpected self-synthesized methyl monoester of the acid as an adduct molecule giving one-dimensional hydrogen-bonded chains. In all three structures the hydrogen phthalate anions are