Cytotoxic Compounds from Aloe megalacantha

Abdissa Ayana N, Gohlke S, Frese M, Sewald N. Cytotoxic Compounds from Aloe megalacantha. Molecules. 2017;22(7): 1136.Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC50 = 0.98 µM) being the most active compound

Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae)

Ateba JET, Toghueo RMK, Awantu AF, et al. Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae). JOURNAL OF FUNGI. 2018;4(2): UNSP 70.There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC50 < 10 mu g.mL(-1)) with three fungi including Paecilomyces lilacinus (IC50 = 0.44 mu g.mL(-1)), Penicillium janthinellum (IC50 = 0.2 mu g.mL(-1)), and Paecilomyces sp. (IC50 = 0.55 mu g.mL(-1)) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing

Compounds from <em>Terminalia mantaly</em> L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against some Pathogenic Yeasts and Enzymes of Metabolic Significance<strong></strong>

Tchuenmogne MAT, Ngouana TK, Gohlke S, et al. Compounds from &lt;em&gt;Terminalia mantaly&lt;/em&gt; L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against some Pathogenic Yeasts and Enzymes of Metabolic Significance&lt;strong&gt;&lt;/strong&gt;. Preprints. 2016.The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-&amp;alpha;-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-o&amp;iuml;c acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-o&amp;iuml;c acid glucopyranoside (4), 2&amp;alpha;,3&amp;alpha;,24-trihydroxyolean-11,13(18)-dien-28-o&amp;iuml;c acid (5), stigmasterol (6), stigmasterol 3-O-&amp;beta;-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 &amp;micro;g/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC50 values below 4 &amp;micro;M and inhibitory constant (Ki) &amp;lt;3 &amp;micro;M.</jats:p

Structure-based prediction of Wnt binding affinities for Frizzled-type cysteine-rich domain

Wnt signaling pathways are of significant interest in development and oncogenesis. The first step in these pathways typically involves the binding of a Wnt protein to the cysteine-rich domain (CRD) of a Frizzled receptor; Wnt-Frizzled interactions can be antagonized by secreted Frizzled-related proteins (sFRPs), which also contain a Frizzled-like CRD. The large number of Wnts, Frizzleds and sFRPs, as well as the hydrophobic nature of Wnt, pose challenges to laboratory-based investigations of interactions involving Wnt. Here, utilizing structural knowledge of a representative Wnt-Frizzled CRD interaction, as well as experimentally-determined binding affinities for a selection of Wnt-Frizzled CRD interactions, we generate homology models of Wnt-Frizzled CRD interactions and develop a quantitative structure-activity relationship for predicting their binding affinities. The derived model incorporates a small selection of terms derived from scoring functions used in protein-protein docking, as well as an energetic term considering the contribution made by the lipid of Wnt to the Wnt-Frizzled binding affinity. Validation with an external test set suggests that the model can accurately predict binding affinity for 75% of cases, and that the error associated with the predictions is comparable to the experimental error. The model was applied to predict the binding affinities of the full range of mouse and human Wnt-Frizzled and Wnt-sFRP interactions, indicating trends in Wnt binding affinity for Frizzled and sFRP CRDs. The comprehensive predictions made in this study provide the basis for laboratory-based studies of previously unexplored Wnt-Frizzled and Wnt-sFRP interactions, which in turn, may reveal further Wnt signaling pathways

Array programming with NumPy.

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis

Cytotoxic Compounds from Aloe megalacantha

Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC50 = 0.98 µM) being the most active compound

40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug

Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of Dysidea species in 1981 and have been under continuous research to the present day. This article summarizes the two research aspects, (i) the marine compound chemistry research dealing with naturally produced PBDEs and (ii) the environmental toxicology research dealing with synthetically-produced brominated flame-retardant PBDEs. The different bioactivity patterns are set in relation to the structural similarities and dissimilarities between both groups. In addition, this article gives a first structure–activity relationship analysis comparing both groups of PBDEs. Moreover, we provide novel data of a promising anticancer therapeutic PBDE (i.e., 4,5,6-tribromo-2-(2′,4′-dibromophenoxy)phenol; termed P01F08). It has been known since 1995 that P01F08 exhibits anticancer activity, but the detailed mechanism remains poorly understood. Only recently, Mayer and colleagues identified a therapeutic window for P01F08, specifically targeting primary malignant cells in a low µM range. To elucidate the mechanistic pathway of cell death induction, we verified and compared its cytotoxicity and apoptosis induction capacity in Ramos and Jurkat lymphoma cells. Moreover, using Jurkat cells overexpressing antiapoptotic Bcl-2, we were able to show that P01F08 induces apoptosis mainly through the intrinsic mitochondrial pathway

Infection control and outcome of staged reverse shoulder arthroplasty for the management of shoulder infections

Background The treatment of septic arthritis, caused by either hematogenous seeding, injections, or surgery, can be challenging. Staged reverse shoulder arthroplasty (RSA) with temporary implantation of an antibiotic-loaded spacer is widely accepted but still discussed controversially. This study investigated the shoulder-specific bacterial spectrum, infection control rate, functional outcome, and infection-free survival rate after staged RSA in the mid- to long-term follow-up. It was hypothesized that staged RSA would show a high infection-free survival rate. Methods A total of 39 patients treated with staged RSA for primary septic arthritis (n = 8), secondary infection (n = 8), or periprosthetic infection (n = 23) were retrospectively included. The infection control rate was calculated based on cultures taken intraoperatively at spacer removal and RSA implantation. Infection-free survival was defined as no revision due to infection. The minimum follow-up period for functional outcome assessment was 2 years (n = 14; mean, 76 months; range, 31-128 months). Results Cutibacterium (26%) and coagulase-negative staphylococci (23%) were the predominant pathogens. The infection control rate was 90%. The cumulative infection-free survival rate was 91% after 128 months. Follow-up examinations showed a mean Constant score of 48 (range, 7-85), a mean QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score of 40.0 (range, 11.4-93.3), and a mean pain score of 1.6 (range, 0-7). Conclusion Staged RSA implantation was confirmed to be a reliable treatment option for primary, secondary, and periprosthetic infections of the shoulder. The infection control rate and infection-free survival rate are satisfactory. However, patients and surgeons must be aware of functional impairment even after successful treatment of infections