15196-28-8

In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC50 below 10 μm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.

Three series of d-galactose derivatives linked to a lipophilic aminoalcohol moiety were synthesized and their antibacterial activity was evaluated against Mycobacterium tuberculosis and representative species of Gram positive and Gram negative bacteria. Five out of the thirteen tested compounds displayed activity against M. tuberculosis, with a minimal inhibitory concentration (MIC) of 12.5 μg/mL and seven compounds were active against the four bacterial strains tested. The best results were obtained for amino alcohols 10 and 11 against Staphylococcus epidermidis (MIC Combining double low line 2 μg/mL). The antitumor activity was evaluated against three tumor cell lines (MCF-7, HeLa and MO59J) and compared to the normal cell line GM07492A. The results showed that the lowest IC50 values were observed for the amino alcohol 16 against MCF-7 (11.9 μM) and MO59J (10.0 μM).

Dermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive. Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause dermatomycoses. The minimum inhibitory concentrations (MICs) and the minimum fungicidal concentration (MFC) of aminoalcohol (1–4) and diamine (5–13) derivatives was determined against Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum, and Candida albicans according to protocols from the Clinical and Laboratory Standards Institute. All molecules exhibited fungicidal activity against the evaluated fungal strains, with the MIC and MFC ranging between 0.12 and 1000 μg/mL for filamentous fungi and 0.6 and 1250 μg/mL for yeasts. The best activity was attributed to diamines compared to aminoalcohols, with an emphasis on molecules 6 and 7. These results demonstrate the antifungal potential of the evaluated aminoalcohols and diamines against the four primary fungal species that cause dermatomycoses. [Figure not available: see fulltext.]

To the invention, 9 - 2, 2, 6 tetramethylpiperidine oxide (TEMPO) is used as an oxidizing agent, the reaction temperature 6 - is lower, Fmoc-Cl is protected and oxidized to obtain N - (0 °C fluorenylmethoxycarbonyl) decyl aminoacetaldehyde. TEMPO oxidation is simple, the reaction temperature is mild, pH value and reaction temperature of the reaction liquid are controlled. (by machine translation)

Provided are a class of vancomycin derivatives with a structure as shown in the general formula below and pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition containing the compound thereof, and the use of these compounds in preparing drugs for treating and/or preventing bacterial infection diseases, in particular drugs for treating infection diseases caused by Gram-positive bacteria.

Lipophilic substitution on vancomycin is an effective strategy for the development of novel vancomycin analogues against drug-resistant bacteria by enhancing bacterial cell wall interactions. However, hydrophobic structures usually lead to long elimination half-life and accumulative toxicity; therefore, hydrophilic fragments were also introduced to the lipo-vancomycin to regulate their pharmacokinetic/pharmacodynamic properties. Here, we synthesized a series of new vancomycin analogues carrying various sugar moieties on the seventh-amino acid phenyl ring and lipophilic substitutions on vancosamine with extensive structure-activity relationship analysis. The optimal analogues indicated 128-1024-fold higher activity against methicillin-susceptible S. aureus, vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE) compared with that of vancomycin. In vivo pharmacokinetics studies demonstrated the effective regulation of extra sugar motifs, which shortened the half-life and addressed concerns of accumulative toxicity of lipo-vancomycin. This work presents an effective strategy for lipo-vancomycin derivative design by introducing extra sugars, which leads to better antibiotic-like properties of enhanced efficacy, optimal pharmacokinetics, and lower toxicity.

Novel lipophilic gold(I) complexes containing 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione derivatives were synthesized and characterized by IR, high resolution mass spectrometry, and 1H, 13C 31P NMR. The cytotoxicity of the compounds was evaluated considering cisplatin and/or auranofin as reference in different tumor cell lines: colon cancer (CT26WT), metastatic skin melanoma (B16F10), breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), glioblastoma (M059?J). Normal human lung fibroblasts (GM07492-A) and kidney normal cell (BHK-21) were also evaluated. The gold(I) complexes were more active than their respective free ligands and cisplatin. Furthermore, antibacterial activity was evaluated against Gram-positive bacteria Staphylococcus aureus ATCC 25213, Staphylococcus epidermidis ATCC 12228 and Gram-negative bacteria Escherichia coli ATCC 11229 and Pseudomonas aeruginosa ATCC 27853 and expressed as the minimum inhibitory concentration (MIC). The complexes exhibited lower MIC values when compared to the ligands and chloramphenicol against Gram-positive bacteria and Gram-negative bacteria. Escherichia coli was sensitive one to the action of gold(I) complexes.

Compounds useful in the preparation of telavancin, for example, were prepared. These compounds include decylaminoethanal dialkyl acetals and N-protected decylaminoethanal dialkyl acetals, imidazolidine derivatives, and N-protected- decylaminoethanal.

A series of N- and C-alkylated amino alcohols and of their protected galactopyranosyl derivatives was synthesized and evaluated for antitubercular activity. Five of these compounds displayed good activity, with a MIC below 12.5 μg/mL. The presence of the carbohydrate slightly affected the antibacterial activity.

Disclosed are derivatives of glycopeptide antibiotic compounds having at least one substituent of the formula: —Ra—Y—Rb—(Z)x where Ra, Rb, Y, Z and x are as defined, and having a group W at the glucose C-6 position, where W is as defined; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

Novel antibacterial agents that act as multibinding agents are disclosed. The compounds of the invention comprise from 2-10 ligands covalently connected, each of said ligands being capable of binding to a transglycosylase enzyme substrate thereby modulating the biological processes/functions thereof.

Disclosed are derivatives of glycopeptide compounds having at least one substituent of the formula: —Ra—Y—Rb—(Z)x where Ra, Rb, Y, Z and x are as defined, and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

A process for the preparation of polyoxyalkylated compounds comprising at least one primary or secondary amine function is provided comprising reacting at least one amino-alcoholate (B) produced from an amino-alcohol (A) including at least one OH group and at least one primary or secondary amine function, by replacing a fraction or all the OH groups by OM groups, M being selected from sodium, potassium, rubidium and cesium, with an oxirane, a mixture of oxiranes or a sequence of oxiranes, in an aprotic and anhydrous solvent, in an anhydrous atmosphere and at a temperature of between about 0° C. and 200° C.