In vitro biological effects of two anti-diabetic medicinal plants used in Benin as folk medicine.

Background: Extracts from Polygonum senegalensis (Polygonaceae) and Pseudocedrela kotschyi (Meliaceae) are two important traditionally used medicinal plants in rural Benin to treat many diseases and notably type 2 diabetes. The aim of the study was to investigate the α-glucosidase inhibition, antioxidant and antibacterial activities of those plants extract: Polygonum senegalensis leaves, and Pseudocedrela kotschyi root.

Methods: Hydro-alcoholic (50%) extracts were analyzed for their phytochemical content and tested for their inhibition potency on α-glucosidase from Saccharomyces cerevisiae.

Imidazonaphthyridine systems (part 2): Functionalization of the phenyl ring linked to the pyridine pharmacophore and its replacement by a pyridinone ring produces intriguing differences in cytocidal activity.

We recently discovered that five- and pseudo-five-fused-ring derivatives in an imidazonaphthyridine series were promising hit compounds for the development of new DNA-intercalators. In this study, novel (dihydro)imidazo[1,6] and [1,7]naphthyridi(no)nes were prepared including pseudo-pentacycles. All the compounds synthesized were screened against four tumor cell lines.

Design and preparation of aza-analogues of benzo[c]phenanthridine framework with cytotoxic and antiplasmodial activities.

Benzo[c]phenanthridine alkaloids represent interesting lead for the discovery of new potential antiplasmodial and/or anticancer drugs. In this field, a novel library of aza-analogs of benzo[c]phenanthroline framework derivatives was designed and prepared. Although these compounds did not have specific antiplasmodial activities, some of them displayed specific in vitro activity against two cancer lines especially compound 24 with an IC(50) against the MCF7 line of 0.

Synthesis and antiviral activity of an imidazo[1,2-a]pyrrolo[2,3-c]pyridine series against the bovine viral diarrhea virus.

A series of imidazo[1,2-a]pyrrolo[2,3-c]pyridines has been prepared and evaluated for their anti-BVDV activities in MDBK cells. From the synthesized analogues bearing modifications of the substituents at positions 2, 3, 7 and 8, compounds 10a, b, 16, 24, 25 and 26 exhibited significant anti-BVDV activities.

A pyrazolotriazolopyrimidinamine inhibitor of bovine viral diarrhea virus replication that targets the viral RNA-dependent RNA polymerase.

[7-[3-(1,3-Benzodioxol-5-yl)propyl]-2-(2-furyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] (LZ37) was identified as a selective inhibitor of in vitro bovine viral diarrhea virus (BVDV) replication. The EC(50) values for inhibition of BVDV-induced cytopathic effect (CPE) formation, viral RNA synthesis and production of infectious virus were 4.3+/-0.

Synthesis and antituberculosis activity of new hydrazide derivatives.

The increasing clinical importance of drug-resistant mycobacterial pathogens, especially Mycobacterium tuberculosis, has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new hydrazide derivatives of imidazo[1,2-a]pyridine were synthesized and evaluated for antituberculosis activity. The reaction of 2-[(2-carboxyimidazo[1,2-a]pyridine-3-yl)sulfanyl]acetic acid hydrazide with various benzaldehydes gave N-(arylidene)-2-[(2-carboxyimidazo[1,2-a]pyridine-3-yl)sulfanyl]acetic acid hydrazide derivatives.

Design, synthesis and preliminary biological evaluation of acridine compounds as potential agents for a combined targeted chemo-radionuclide therapy approach to melanoma.

Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy.

Design, synthesis, and biological activities of conformationally restricted analogs of primaquine with a 1,10-phenanthroline framework.

A series of primaquine analogs was prepared, according to a conformationally restricted conformation of primaquine. In vitro antiplasmodial activities were evaluated and showed that all compounds were active on different strains of Plasmodium falciparum. In particular compounds 5 and 15 possessing a methoxy group were more active than was primaquine.

New opportunities with the Duff reaction.

The Duff reaction (HMTA, AcOH or TFA) was studied on substituted [6 + 5] heterocyclic compounds. This reaction provides a useful route to aldehydes for compounds bearing sensitive amide functions. It gives also access to tricyclic lactams of potential biological interest.

Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma.

Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest.

Novel imidazo[1,2-a]naphthyridinic systems (part 1): synthesis, antiproliferative and DNA-intercalating activities.

Novel imidazo[1,2-a]naphthyridinic systems 6a-15a and 6b-15b were obtained from Friedländer's reaction in imidazo[1,2-a]pyridine series. Most of the compounds were evaluated for their antitumor activity in the NCIs in vitro human tumor cell line screening panel. Among them, pentacyclic derivatives 13b and 14a exhibited in vitro activity comparable to anticancer agent such as amsacrine.

Synthesis and biological evaluation of indoloquinolines and pyridocarbazoles: a new example of unexpected photoreduction accompanying photocyclization.

Indoloquinoline alkaloid cryptolepine and pyridocarbazole alkaloid ellipticine are of great interest because in vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically active analogs of these compounds, we developed a synthesis based on the photocyclization of tertiary N-substituted enaminones derived from 1,3-cyclohexandione and 3 or 6-aminoquinoline. The angular cyclized compounds thus obtained were tested in vitro on K 562 cells and A 2780 doxorubicin sensitive and resistant cells.

The imidazopyrrolopyridine analogue AG110 is a novel, highly selective inhibitor of pestiviruses that targets the viral RNA-dependent RNA polymerase at a hot spot for inhibition of viral replication.

Ethyl 2-methylimidazo[1,2-a]pyrrolo[2,3-c]pyridin-8-carboxylate (AG110) was identified as a potent inhibitor of pestivirus replication. The 50% effective concentration values for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect, viral RNA synthesis, and production of infectious virus were 1.2 +/- 0.

N-Phenyl-N'-(2-chloroethyl)urea analogues of combretastatin A-4: Is the N-phenyl-N'-(2-chloroethyl)urea pharmacophore mimicking the trimethoxy phenyl moiety?

A series of novel N-phenyl-N'-(2-chloroethyl)urea derivatives potentially mimicking the structure of combretastatin A-4 were synthesized and tested for their cell growth inhibition and their binding to the colchicine-binding site of beta-tubulin. Compounds 2a, 3a, and 3b were found to inhibit cell growth at the micromolar level on four human tumor cell lines. Flow cytometric analysis indicates that the new compounds act as antimitotics and arrest the cell cycle in G(2)/M phase.

In vitro and in vivo antimalarial activity of derivatives of 1,10-phenanthroline framework.

A series of trisubstituted 1,10-phenanthrolines was prepared. These compounds exhibited mild to high biological activities in vitro both toward chloroquino-resistant FcB1-Columbia and FcM29-Cameron strains and Nigerian chloroquino-sensitive strain of Plasmodium falciparum. Cytotoxicity of the most active compounds was estimated showing that one compound (10) exhibited a selective activity against malaria parasite (selectivity indexes of 52 and 144).

A photochemical approach to pyridopyrroloquinoline derivatives as new potential anticancer agents.

Indoloquinoline alkaloid cryptolepine and pyridocarbazole alkaloid ellipticine are of great interest because in vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically active analogs of these compounds, we developped a synthesis based on the photocyclisation of tertiary N-methylated enaminones derived from cyclopentane-1,3-dione and 3 or 6-aminoquinoline. The angular cyclised compounds thus obtained were submitted to Beckmann rearrangement, preceded by the formation of a Z oxime.