(S)-(2-(2'-Pyridyl)ethyl)cysteamine and (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine as ligands for the "fac-[M(CO)(3)](+)" (M = Re, (99m)Tc) core.

The reaction of fac-[NEt(4)](2)[Re(CO)(3)Br(3)] with (S)-(2-(2'-pyridyl)ethyl)cysteamine, L(1), in methanol leads to the formation of the cationic fac-[Re(CO)(3)(NSN)][Br] complex, 1, with coordination of the nitrogen of the pyridine, the sulfur of the thioether, and the nitrogen of the primary amine. When fac-[NEt(4)](2)[Re(CO)(3)Br(3)] reacts with the homocysteine derivative (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine, L(2), the neutral fac-Re(CO)(3)(NSO) complex, 2, is produced with coordination of the nitrogen of the primary amine, the sulfur of the thioether, and the oxygen of the carboxylate group, while the pyridine ring remains uncoordinated. The analogous technetium-99m complexes, 1' and 2', were also prepared quantitatively by the reaction of L(1) and L(2) with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor at 70 degrees C in water. Given that both (S)-(2-(2'-pyridyl)ethyl)cysteamine and homocysteine can be easily N- or S-derivatized by a bioactive molecule of interest, both the NSN or NSO ligand systems could be used to develop target-specific radiopharmaceuticals for diagnosis and therapy.

Synthesis and biological evaluation of indole containing derivatives of thiosemicarbazide and their cyclic 1,2,4-triazole and 1,3,4-thiadiazole analogs.

New indolic derivatives of thiosemicarbazides and some cyclic 1,2,4-triazol-5-thione analogs were synthesized. The newly synthesized compounds as well as some indole containing thiosemicarbazides, 1,2,4-triazoles and 1,3,4- thiadiazoles, which have been reported previously, were investigated for antimicrobial, antifungal and antiphage activity. Certain thiosemicarbazide derivatives and the corresponding cyclic 1,2,4-triazole analogs showed selective antimicrobial or antifungal activity, while they lack any antiphage activity. Antiphage activity was detected for one compound, bearing the 1,3,4-thiadiazole nucleus. The selectively active compounds cover a wide range of lipophilicity. Structure-activity relations show a remarkably similarity in the antimicrobial and antifungal behaviour of the thiosemicarbazides and their cyclic triazo-thien-5-yl analogs, while alpha-naphtyl substitution in the non indolic portion of the molecule is favorable. C5 substitution on the indolic nucleus may also be critical for selective activity.

Synthesis, lipophilicity and biological evaluation of indole-containing derivatives of 1,3,4-thiadiazole and 1,2, 4-triazole.

3-[(2-Methyl-1H-3-indolyl) methyl]-4-aryl-4, 5-dihydro-1H-1,2,4-triazole-5-thiones 6a-c and their respective N-¿5-[2-methyl-1H-3-indolyl) methyl]-1,3,4-thiadiazol-2-yl¿-N-arylamines 7a,b have been prepared. The antidepressant profile of 6a,c and 7a was studied on mice with respect to that of the analogous 3-(1H-1-indolylmethyl)-4-aryl-4,5-dihydro-1H-1,2,4-triazole-5-thio nes 1a-c and the respective N-¿5-[(2-methyl-1H-3-indolyl) methyl]-1,3,4-thiadiazole-2-yl¿-N-arylamines 2a-c, the synthesis and antimicrobial potency of which we have recently reported. Behavioral effects, induced by the members of both series, in conjunction with their activity in some specific tests (forced swim, pentetrazole convulsions) on mice, show that these derivatives cross the blood-brain barrier and could develop an antidepressant activity comparable to that of imipramine. Blood-brain barrier penetration is also supported by the lipophilicity data obtained for all analogs.

Synthesis and antimicrobial evaluation of indole containing derivatives of 1,3,4-thiadiazole, 1,2,4-triazole and their open-chain counterparts.

The increasing clinical importance of drug-resistant bacterial pathogens has lent additional urgency to microbiological and antibacterial research. New indolic derivatives of triazoles, thiadiazoles and their respective open-chain thiosemicarbazides were evaluated for antibacterial and antifungal activity. The microorganisms used were the Gram-negative bacteria Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853, the Gram-positive bacteria Staphylococcus aureus ATCC 25923 and Bacillus subtilis BBL 12084 and the yeasts Candida and Saccharomyces cerevisiae ATCC 2366. The most potent compounds were indole derivatives (12a-c) bearing 1,2,4-triazo-thien-5-yl moiety, which exhibit interesting antibacterial and antifungal activities.

A novel series of DNA triple helix-binding ligands.

We have examined the effect of a series of substituted imidazothioxanthones on the stability of an intermolecular DNA triple helix by DNase I footprinting. We find that several of these compounds promote the formation of a complex between T5C5 and the target site A6G6.C6T6, suggesting that they bind specifically to triplex DNA. The only inactive derivative lacked a protonatable function in the side chain, suggesting that this is an essential feature for triplex stabilization. These compounds, which are amongst the first triplex-binding ligands which possess an uncharged chromophore, are selective for the T.AT rather than the C+.GC triplet.

Synthesis and anticancer activity of new phenyl-ring substituted 4-morpholino-1-phenylthio-2-butanones [Mannich bases].

The preparation of phenyl-ring substituted 4-morpholino-1-phenylthio-2-butanones 4a-e is described. These compounds were evaluated against P-388 leukemia and human cancer rhinopharynx KB cells in vitro; some compounds were found to exhibit activity against these cell lines.

Synthesis, lipophilicity studies and antibacterial properties of some novel quaternary ammonium salts.

The synthesis of some novel quaternary ammonium salts, derivatives of 15-phenyl-decapentanoic acid, is described. Their lipophilicity was estimated applying the Hansch-Leo fragmental procedure and measured by means of reversed phase thin layer chromatography. All compounds were tested for their antibacterial activity against Gram positive and gram negative microorganisms. The less lipophilic compounds showed weak activity, mainly against gram positive microorganisms.

[Synthesis of new nitrosoureas]. / Synthèse de nouvelles nitrosourées.

Two chemical pathways were used for the synthesis of three new N'-(2-chloroethyl)-N-[2-(4-alkoxyphenylthio)ethyl]-N'-nitrosoureas and two new N'-(2-chloroethyl)-N)[2-(4-alkoxyphenyl-thio)ethyl]-N-nitrosoureas . The study of the cytotoxicity of the three N'-nitrosoureas, was carried out in two experimental models (P 388 and NSCLCN6).

[Synthesis and anticonvulsive activity of some new bisubstituted 1,3,4-oxadiazoles and 1H-1,2,4-triazoles]. / Synthèse et activité anticonvulsivante de quelques nouveaux oxadiazoles-1,3,4 et 1H-triazoles-1,2,4 disubstitués.

The synthesis of 7 new 2-[(2-alkoxy-3-methoxyphenyl) methyl]-5-arylamino-1,3,4 oxadiazoles by cyclisation of the corresponding thiosemicarbazides is described. Some of these were tested for anticonvulsant activity. The compound 2-[(2-butoxy-3-methoxy phenyl) methyl]-5-phenylamino 1,3,4-oxadiazole has shown significant anticonvulsant potency. A few new 3-phenyl-5-[(2-alkoxy-3-methoxy phenyl) methyl]-1H-1,2,4 triazoles have also been synthesized.