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

Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: Diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole

International audienceCryptococcal meningitis is a mycosis encountered especially in patients with Acquired Immunodeficiency Syndrome and is fatal in the absence of treatment. Information on epidemiology, diagnosis and susceptibility profile to antifungal drugs, are scarce in Cameroon. Authors evaluated the diagnosis possibilities of the cryptococcal meningitis in Cameroon, and studied the antifungal susceptibility of isolated strains to fluconazole, used as first line treatment of the disease in Cameroon. Between December 2009 and July 2011, 146 cerebrospinal fluids obtained from HIV patients with suspicion of meningitis were analysed. The diagnosis procedure involved macroscopic and cyto-chemical analysis, India ink test, culture on Sabouraud chloramphenicol medium and antigen latex agglutination test. Antifungal susceptibility testing of isolated strains to fluconazole was done by the E-test(®) method. The diagnosis of cryptococcal meningitis gave 28.08% positive cases. Among these patients, 80% were at stages III and IV and 20% at stage I of the HIV infection, according to the WHO previous classification. Cyto-chemical analysis showed current findings in the case of cryptococcal meningitis. India ink test and latex agglutination test exhibited very high sensitivity and specificity (>94%). Fluconazole antifungal susceptibility testing gave MICs lower than 32μg/mL to 92.7% of isolated strains and MICs greater than this value to 7.3% of isolates. These results showed that cryptococcal meningitis remains a real problem among HIV infected patients in Yaoundé. The emergence of fluconazole reduced susceptibility strains is worrying. Nevertheless, efficacy of rapid detection tests is interesting because this will help in rapid diagnosis and treatment of patients

Genotyping and antifungal susceptibility testing of Cryptococcus neoformans isolates from Cameroonian HIV-positive adult patients

Cryptococcus neoformans is the most common cause of meningitis amongst adult Africans with HIV/AIDS. The widespread use of fluconazole may lead to the emergence of isolates with reduced susceptibility. We studied C.neoformans isolates from HIV-infected patients with cryptococcal meningitis. Genotyping and antifungal testing were performed to assess the genetic diversity, occurrence of mixed infections and in vitro activity of antifungal agents. Isolates were recovered from cerebrospinal fluid prior to systemic antifungal treatment. Six isolates were studied for each sample (a total of 114 isolates from 19 patients). Serotyping was performed via LAC 1 and CAP 64 gene amplification and genotyping was performed using phage M13 core, (GACA)(4) and (GTG)(5) primers and restriction polymorphism analysis of the URA5 gene. Susceptibilities for amphotericin B, flucytosine, fluconazole, voriconazole and posaconazole were tested by the Sensititre YeastOne (R) method. All strains were identified as C.neoformans var. grubii serotype A. We identified nine major genotypes. Up to two genotypes were identified in the same sample. None of the isolates were resistant to the studied drugs. However, 13 of 114 strains exhibited a reduced susceptibility to fluconazole and 13 of 114 strains exhibited a reduced susceptibility to flucytosine. No correlation was found between the genotype and susceptibility. This study confirms the prevalence of C.neoformans serotype A in Cameroon. Two genotypes may be responsible for a single episode of cryptococcosis. The possibility of mixed infection and diminished susceptibility to fluconazole or flucytosine must be considered for the management of cryptococcosis

Structural Arrangements of Isomorphic Substitutions in Smectites: Molecular Simulation of the Swelling Properties, Inter layer Structure, and Dynamics of Hydrated Cs-Montmorillonite Revisited with New Clay Models

International audienceThree new structural models of montmorillonite with differently distributed Al/Si and Mg/Al substitutions in the tetrahedral and octahedral clay layers are systematically developed and studied by means of MD simulations to quantify the possible effects of such substitutional disorder on the swelling behavior, the interlayer structure, and mobility of aqueous species. A very wide range of water content, from 0 to 700 mg(water)/g(clay) is explored to derive the swelling properties of Cs-montmorillonite. The determined layer spacing does not differ much depending on the clay model. However, at low water contents up to 1-layer hydrate (similar to 100 mg(water)/g(clay)) the variation of specific locations of the tetrahedral and octahedral substitutions in the two TOT clay layers slightly but noticeably affects the total hydration energy of the system. Using atom-atom radial distribution functions and the respective atomic coordination numbers we have identified for the three clay models not only the previously observed binding sites for Cs+ on the clay surface but also new ones that are correlated with the position of tetrahedral substitution in the structure. The mobility of Cs+ ions and H2O diffusion coefficients, as expected, gradually increase both with increasing water content and with increasing distance from the clay surface, but they still remain 2 to 4 times lower than the corresponding bulk values. Only small differences were observed between the three Cs-montmorillonite models, but these differences are predicted to increase in the case of higher charge density of the clay layers and/or interlayer cations