Truncated Lie groups and almost Klein models

We consider a real analytic dynamical system G×M→M with nonempty fixed point subset M ^G . Using symmetries of G×M→M, we give some conditions which imply the existence of transitive Lie transformation group with G as isotropy subgroup.     

Endodesmiadiol, a friedelane triterpenoid, and other antiplasmodial compounds from Endodesmia calophylloides

From the ethyl acetate extract of the stem bark of Endodesmia calophylloides (Guttiferae), a novel friedelane triterpenoid named endodesmiadiol (1), as well as the known compounds friedelin (2), canophyllol (3), canophyllal (4), cerin (5), morelloflavone (6), volkensiflavone (7), 8-deoxygartanin (8), 3 beta-acetoxyoleanolic acid (9) and 1,8-dihydroxy-3-isoprenyloxy-6-methylxanthone (10) have been isolated. The structures of these compounds were established by spectroscopic analysis, and the relative configuration of endodesmiadiol (1) was confirmed by X-ray diffraction. The antiplasmodial activity of the isolated compounds was evaluated against the W2 strain of Plasmodium falciparum which is resistant to chloroquine and other antimalarial drugs. All the compounds were found to be active with IC50 values ranging from 7.2 to 23.6 microM. The IC50 of endodesmiadiol was found to be 11.8 microM.     

Local structure of Koszul-Vinberg and of Lie algebroids

In this short note we continue our study of Koszul-Vinberg algebroids which form a subcategory of the category of Lie algebroids, and which appear naturally in the study of affine structures, affine and transversally affine foliations [N. Nguiffo Boyom, R. Wolak, J. Geom. Phys. 42 (2002) 307-317]. We prove a local decomposition theorem for KV-algebroids. Using the notion of KV-algebroids we introduce a new class of singular foliations: affine singular foliations. In the last section we study the holonomy of these foliations and prove a stability theorem.     

Cholinesterase inhibiting and antiplasmodial steroidal alkaloids from Sarcococca hookeriana

Bioguided phytochemical investigation of Sarcococca hookeriana with respect to the cholinesterase enzyme inhibitory assay yielded two new pregnane-type steriodal alkaloids hookerianamide H (1) and hookerianamide I (2), along with three known alkaloids N(a)-methylepipachysamine D (3), sarcovagine C (4) and dictyophlebine (5). Their structures were determined with the aid of extensive spectroscopic analysis. All compounds showed good inhibitory activities against the enzymes acetylcholinesterase (IC(50) 2.9-34.1 microM) and butyrylcholinesterase (IC(50) 0.3-3.6 microM). These compounds also showed moderate antiplasmodial activity (IC(50) 2.4-10.3 microM) against the Plasmodium falciparum chloroquine resistant W2 strain.     

Anti-plasmodial activity of some constituents of the root bark of Harungana madagascariensis LAM. (Hypericaceae)

Bazouanthrone (1), a new anthrone derivative, has been isolated from the root bark of Harungana madagascariensis, together with known compounds, feruginin A (2), harunganin (3), harunganol A (4), harunganol B (5), friedelan-3-one (6) and betulinic acid (7). The structure of the compound (1) was assigned as 3,5,8,9-tetrahydroxy-2,4,4-tri-(3,3-dimethylallyl)-6-methyl-1-(4H)-anthracenone, by means of spectroscopic analysis. The anti-plasmodial activity of the isolated compounds was evaluated in culture against W2 strain of Plasmodium falciparum. All the compounds were found to be active against the Plasmodium parasites with bazouanthrone (1) showing particular potency (IC50=1.80 microM).     

Varietes symplectiques affines

We will be concerned with two open questions in symplectic geometry. The first question is the existence problem for lagrangian foliations. The second question is to know whether an affine manifold can be embedded as leaf of a lagrangian foliation. We prove that every homogeneous symplectic manifold with closed regular action of a solvable Lie group has lagrangian foliations. Moreover such manifold (M,) has a bilagrangian linear connection (M,) such that is parallel with respect to . About the second question, we prove that every connected and simply connected Lie group with left invariant affine structure can be embedded as leaf of a left invariant lagrangian foliation in a symplectic Lie group (G,).     

Anti-plasmodial and cholinesterase inhibiting activities of some constituents of Psorospermum glaberrimum

Glaberianthrone (1), a new bianthrone was isolated from the hexane extract of the stem bark of Psorospermum glaberrimum together with thirteen known compounds: 3-geranyloxyemodin anthrone (2), friedelan-3-one (3), 3-prenyloxyemodin anthrone (4), 3-geranyloxyemodin (5), 3-prenyloxyemodin (6), friedelan-3-ol (7), acetylvismione D (8), betulinic acid (9), 2-geranylemodin (10), bianthrone A2b (11), bianthrone 1a (12), emodin (13) and 2-prenylemodin (14). The structures of the isolated compounds were established by means of spectroscopic methods. The extracts and the isolated compounds were tested in vitro for their anti-plasmodial activity against Plasmodium falciparum (chloroquine resistant strain W2) and for their acetyl- and butyrylcholinesterase inhibitory properties. The n-hexane extract showed good anti-plasmodial activity against P. falciparum W2 strain, with IC(50) of 0.87 microg/ml. It also exhibited 65.5% and 98.2% of acetyl- and butyrylcholinesterase inhibition at 0.2 mg/ml, respectively. Compounds 2 and 8 showed the best potencies against P. falciparum W2 strain with IC(50) of 1.68 microM and 0.12 microM, (0.66 microg/ml and 0.054 microg/ml) respectively. All tested compounds showed good butyrylcholinesterase inhibition activities with compound 12 displaying the best potency (IC(50) 9.25+/-0.25 microM). All the tested compounds showed weak inhibitory activity against acetylcholinesterase.     

Preliminary Structure–Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors of Trypanosoma brucei brucei

New drugs are urgently needed for the treatment of human African trypanosomiasis (HAT). In line with our quest for novel inhibitors of trypanosomes, a small library of analogs of the antitrypanosomal hit (MMV675968) available at MMV as solid materials was screened for antitrypanosomal activity. In silico exploration of two potent antitrypanosomal structural analogs (7-MMV1578647 and 10-MMV1578445) as inhibitors of dihydrofolate reductase (DHFR) was achieved, together with elucidation of other antitrypanosomal modes of action. In addition, they were assessed in vitro for tentative inhibition of DHFR in a crude trypanosome extract. Their ADMET properties were also predicted using dedicated software. Overall, the two diaminoquinazoline analogs displayed approximately 40-fold and 60-fold more potency and selectivity in vitro than the parent hit, respectively (MMV1578445 (10): IC₅₀ = 0.045 µM, SI = 1737; MMV1578467 (7): IC₅₀ = 0.06 µM; SI = 412). Analogs 7 and 10 were also strong binders of the DHFR enzyme in silico, in all their accessible protonation states, and interacted with key DHFR ligand recognition residues Val32, Asp54, and Ile160. They also exhibited significant activity against trypanosome protein isolate. MMV1578445 (10) portrayed fast and irreversible trypanosome growth arrest between 4–72 h at IC₉₉. Analogs 7 and 10 induced in vitro ferric iron reduction and DNA fragmentation or apoptosis induction, respectively. The two potent analogs endowed with predicted suitable physicochemical and ADMET properties are good candidates for further deciphering their potential as starting points for new drug development for HAT.