Antileishmanial activities and mechanisms of action of indole-based azoles.

Two 3-(alpha-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L.

Synthesis and evaluation of disubstituted N1- and N3-imidazolidin-2-ones acting as potential immunosuppressive agents.

New N1-mono and N1, N2-disubstituted imidazolidin-2-one with a significant immunosuppressive activity have been discovered. Among the 17 synthesized and tested compounds, five of them showed maximal inhibition of proliferation of concanavallin A (Con A)- stimulated splenocytes at 90 microM, identical to that obtained with cyclosporin A (CsA) at 5 microM, an optimal concentration.

Synthesis and antileishmanial activity of new imidazolidin-2-one derivatives.

N(3)-acyl, arylsulfonyl and benzyl derivatives of N(1)-(4,6-dimethylpyridin-2-yl), (5-methylthiazol-2-yl) or (3-methylisoxazol-5-yl)imidazolidin-2-ones were synthesized and evaluated as potential antileishmanial agents. Determination of their cytotoxic effect was carried out using MRC5 cells. Two compounds, 1-(4,6-dimethylpyridin-2-yl)-3-(napht-2-ylsulfonyl)imidazolidin-2-one, 18, and 1-(3-methylisoxazol-5-yl)-3-(4-bromobenzyl)imidazo-lidin-2-one, 25, exerted significant antileishmanial activity in promastigotes of Leishmania (L) mexicana and Leishmania infantum, with IC(50) in the range of 8-16 micro mol L(-1).

In vitro activity of a new antifungal azolyl-substituted indole against Aspergillus fumigatus.

A new 2-(alpha-azolylbenzyl)indole derivative exhibited high in vitro activity against 10 strains of Aspergillus fumigatus. This active compound, MT18n, had MIC of 2 microg/mL and is slightly less active than itraconazole and amphotericin B. The mechanism of action of this compound was evaluated through scanning electron microscopy, ergosterol biosynthesis inhibition and phospholipase A2-like activity inhibition studies.

Synthesis and antileishmanial activity of new 1-(pyridin-2-yl)imidazolidin-2-ones derived from 2-amino-4,6-dimethylpyridine.

Derivatives of 2-amino-4,6-dimethylpyridine resulting from the integration of the amino function into a 2-imidazolidinone were synthetized via the corresponding 2-chloroethylurea. N3-benzylation, acylation or sulfonylation afforded the target compounds 6-14 which were evaluated for their in vitro and in vivo antileishmanial activity. Two compounds, the N3-benzyl derivative 7 and the N3-tolylsulfonyl derivative 14, exhibited potent inhibition against cultured extracellular promastigotes of Leishmania mexicana with IC50 comparable to that of the previously studied N-(4,6-dimethylpyridin-2-yl) furan-2-carboxamide 2: 32.

[Synthesis and pharmacologic evaluation of 3-(2- and 4-pyridinyl)indane-1,3-diones and structural analogues with potential anti-inflammatory and antineoplastic activity].

Our on going work in the series of enamido-diketones issued from 2-azaarylindane-1,3-diones led us to synthesize and experiment N and C2-substituted derivatives of 2-(2 and 4-pyridinyl)indane-1,3-diones as well as of structurally related compounds resulting from the replacement of pyridine by quinoline and benzimidazole. Pharmacological evaluation of their anti-inflammatory activity (by inhibition of carrageenan foot edema) and their anticoagulant activity (by prothombin assay) led to the conclusion of the possibility of achieving a selective anti-inflammatory effect. It has been previously established that anticoagulants are liable to exert a protective effect in the development of cancer metastasis.

Synthesis and anti-inflammatory activity of polyazaheterocyclic derivatives of 6-amino-2,4-lutidine and their precursors.

Derivatives of N-(4,6-pyridin-2-yl)arylcarboxamides resulting from the integration of the amidic function into 4H-1,2,4-triazole, triazol-3(2H)-one and 1H-tetrazole rings were evaluated as potential anti-inflammatory compounds. The level of activity decreased as compared to carboxamides, nevertheless their precursors and notably the corresponding amidrazones exhibited potent activity; amidrazone 21, whose ID50 was 34.4 mg.

Cholinesterase inhibition by derivatives of 2-amino-4,6-dimethylpyridine.

Derivatives of 2-amino-4,6-dimethylpyridine, aryl(alkyl)carboxamides, thiocarbamides and amidrazones, already known for their anti-inflammatory properties, were found to be moderately active inhibitors of acetyl and butyrylcholinesterase. Quantitative structure-activity relationships showed that the binding affinity was enhanced by the following structural modifications: (1) increase in molecular volume, (2) decrease in the energy of the lowest unoccupied molecular orbital, (3) insertion of a methylene group between the amide carbonyl and the aromatic ring, (4) replacement of the amide oxygen by sulfur. The affinity remained, however, weaker than that of the specific inhibitor 9-amino-1,2,3,4-tetrahydroacridine (tacrine).