1,2,3-Triazolylalkylribitol derivatives as nucleoside hydrolase inhibitors

A range of novel 1,2,3-triazolylalkylribitol derivatives were synthesized and evaluated as nucleoside hydrolase inhibitors. The most active compound (11a) has low micromolar potency and is structurally diverse from previously reported nucleoside hydrolase inhibitors, which, along with the simplicity of the chemistry involved in its synthesis, makes it a good lead for the further development of novel nucleoside hydrolase inhibitors.     

Antiprotozoal and antiangiogenic saponins from Apodytes dimidiata

Bioassay-guided isolation was performed on the leaves of Apodytes dimidiata E. Mey. Ex Arn. (Icacinaceae), based on previously demonstrated activity against Leishmania. Six saponins never isolated from nature before were elucidated with LC-MS/MS, GC-MS and 1D and 2D NMR. The compounds apodytine A-F are responsible at least in part for the antiprotozoal activity, but also possess haemolytic activity and display antiangiogenic activity in the rat aorta ring assay, an effect which may be due to a non-selective toxicity.     

Antiamoebic and spasmolytic activities of extracts from some antidiarrhoeal traditional preparations used in Kinshasa, Congo.

Three major extracts from some traditional preparations, based on medicinal plants, used as antidiarrhoeal agents were investigated for their putative antiamoebic and spasmolytic activities in vitro. Results indicated that both biological activities are concentrated in the polyphenolic fraction, and not in the saponin or alkaloid containing fractions. The most active polyphenolic extracts were those from Euphorbia hirta whole plant, leaves of Alchornea cordifolia, Crossopteryx febrifuga, Nauclea latifolia, Psidium guajava, Tithonia diversifolia, stem bark of Harungana madagascariensis, Mangifera indica, Maprounea africana and Psidium guajava, inhibiting Entamoeba histolytica growth with MAC < 10 micrograms/ml. The same extracts, at a concentration of 80 micrograms/ml in an organ bath, also exhibited more than 70% inhibition of acetylcholine and/or KCl solution-induced contractions on isolated guinea-pig ileum.     

Antiviral activity of Rwandan medicinal plants against human immunodeficiency virus type-1 (HIV-1)

Selected plants used in Rwandan traditional medicine for the treatment of infections and/or rheumatoid diseases were investigated for antiviral activity in vitro against human immunodeficiency virus type-1 (HIV-1). Of the 38 tested 80% ethanolic extracts, belonging to plants of 21 different families only the extracts from the leaves of Aspilia pluriseta (Asteraceae) and Rumex bequaertii (Polygonaceae) had interesting selectivity indices (SI = ratio of the 50% cytotoxic concentration to the 50% effective antiviral concentration) higher than 1. Further fractionation of the initially antivirally inactive ethanolic extract of Tithonia diversifolia, however, led to an aqueous fraction with a high anti-HIV-1 activity (SI > 461), indicating that the cytotoxicity of some plant components may mask the antiviral properties of the active plant substances in total plant extracts.     

Lignans and neolignans as lead compounds

Many lignans and neolignans have served as lead compounds for the development of new drugs. Perhaps the best known example is podophyllotoxin, an antimitotic compound that binds to tubulin. Etoposide and teniposide are derived from podophyllotoxin, but their antitumoural activity is due to inhibition of topoisomerase II. Combination of both pharmacophores has led to compounds with a dual mechanism of action, such as azatoxin. Dihydrobenzofuran neolignans, based on the natural lead 3,4-di-O-methylcedrusin, have also been investigated as potential antitumoural agents; the dimerisation product of caffeic acid methyl ester was the most active compound. Here too, he cytotoxic activity was due to inhibition of tubulin polymerisation. In addition, the same compounds showed antiangiogenic activity. Podophyllotoxin, as well as other types of lignans, such as dibenzylbutyrolactones related to arctigenin, dibenzocyclooctadiene-type lignans, and dibenzylbutanes, have been explored as leads for antiviral agents (also including HIV). Synthetic 8.O.4-neolignans have been evaluated for their antileishmanial and antifungal properties. Detailed study of the antifungal properties of the phenylpropanoid moieties has resulted in the design of highly active arylpropanoid derivatives. Other examples where lignans have been used as lead compounds include enzyme inhibitors of phosphodiesterase IV and V, and 5-lipoxygenase, and for the development of hypolipidemic and antirheumatic agents.     

Electronic structure calculations as a tool for investigating acyl migrations in ester saponins

The possibility of acyl migrations in ester saponins from Maesa lanceolata was investigated by molecular mechanics and electronic structure calculations carried out on the major constituent maesasaponin IV3 (3beta-O-[[alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-galactopyranosyl-(1-->3)]-[beta-D-galactopyranosyl-(1-->2)]-beta-D-gluco-pyranuronyl]-21beta-angeloyloxy-22alpha-propanoyloxy-13beta,28-oxido-olean-16alpha, 28alpha-diol). It was confirmed that acyl migrations could occur in rings D and E of maesasaponins.     

Antiplasmodial and cytotoxic activities of Striga asiatica and Sauropus spatulifolius extracts,and their isolated constituents

A phytochemical investigation of Striga asiatica and the leaves of Sauropus spatulifolius revealed seventeen compounds, three of which were reported for the first time from nature, i.e. two alkaloids N-hydroxyethyl-2-acetylpyrrole, N-(3-carboxypropyl)-2-acetylpyrrole, and 2-(4-hydroxy-2,2,6-trimethylcyclohexyl)acetic acid, for which the name sauropic acid was adopted. Their structures were established spectroscopically and by single-crystal X-ray diffraction analysis. All extracts and isolates were evaluated for antiplasmodial activity against Plasmodium falciparum strain K1 and for cytotoxicity against MRC-5 cells.     

In vitro propagation of four saponin producing <Emphasis Type="Italic">Maesa</Emphasis> species

A successful micropropagation system was developed for four different medicinal Maesa species. Multiple shoots were induced through both axillary bud formation and adventitious shoot regeneration from leaf explants. The explants were cultured on Murashige and Skoog (MS) medium supplemented with 6-benzyladenine (BA), thidiazuron (TDZ) and/or α-naphthalene acetic acid (NAA). The success of regeneration varied for different species and depended on the type and concentration of plant growth regulators. Regenerated shoots spontaneously developed roots within 6 weeks on MS hormone-free medium. The rooted shoots were transferred to the greenhouse with a 100% success rate. Furthermore, flow cytometry analysis indicated that there were no changes in ploidy level of those regenerated shoots as compared with wild type adult plants. Thin layer chromatography (TLC) analysis revealed that common and distinguishing spot of saponins were similarly observed in regenerated shoots compared to the control plants. Therefore, the protocol also provides an effective means for the in vitro conservation of Maesa spp. that produce pharmaceutically interesting saponins.     

Concentration of Lymph Node Aspirate Improves the Sensitivity of Acid Fast Smear Microscopy for the Diagnosis of Tuberculous Lymphadenitis in Jimma,Southwest Ethiopia

Background

Tuberculous lymphadenitis (TBLN) is the most common form of extrapulmonary tuberculosis. The cytomorphological features of lymph node smears have reduced specificity for the diagnosis of tuberculosis. The diagnosis of TBLN with direct smear microscopy lacks sensitivity due to the limited number of bacilli in lymph node aspirate. Therefore, we aimed to assess whether the concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis.

Methods

A cross-sectional comparative study was conducted on 200 patients clinically suspected for tuberculous lymphadenitis in Jimma, Ethiopia. Lymph node aspirate was collected. The first two drops were used for cytomorphological study and direct acid fast staining. The remaining aspirate was treated with N-acetyl-L-cysteine (NALC) and concentrated by centrifugation at 3000 g for 15 minutes. The sediment was used for acid fast staining and culture. Differentiation of M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM) was done by para-nitrobenzoic acid susceptibility test.

Result

Complete data were available for 187 study subjects. 68% (127/187) were positive for M. tuberculosis on culture. Four isolates, 2.1% (4/187), were identified as NTM. The detection rate of direct smear microscopy was 25.1% and that of the concentration method 49.7%. Cytomorphologically, 79.7% of cases were classified as TBLN. The sensitivity of direct smear microscopy was 34.6%, for concentrated smear microscopy 66.1%, and for cytomorphology 89.8%. Two AFB positive cases on concentration method were non-tuberculosis mycobacteria (NTM). The concentration method yielded a positive result from seven cases diagnosed as suppurative abscess by cytology. Both for the direct and concentration methods the highest rate of AFB positivity was observed in smears showing caseous necrosis alone. Smear positivity rate decreased with the appearance of epithelioid cell aggregates.

Conclusion

The concentration of lymph node aspirates for acid fast smear microscopy had significantly higher sensitivity than direct microscopy.