RESUMEN
Agelasines are 7,9-dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2-position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U-937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC-5 cells. The results indicate that the introduction of a methyl group in the purine 2-position is beneficial for antimycobacterial and antiprotozoal activity, and that amino groups may enhance activity against several cancer cell lines.
Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Antiparasitarios/farmacología , Purinas/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antiparasitarios/síntesis química , Antiparasitarios/química , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Purinas/síntesis química , Purinas/química , Relación Estructura-Actividad , Células VeroRESUMEN
A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantiomeric excess. Structure-activity relationships for two parallel enantiomeric series are described. The (-)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT.
Asunto(s)
Ciclopropanos/síntesis química , Ciclopropanos/farmacología , Proteínas de Transporte de Membrana/efectos de los fármacos , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/antagonistas & inhibidores , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/antagonistas & inhibidores , Diseño de Fármacos , Milnaciprán , Conformación Molecular , Estructura Molecular , Proteínas de Transporte de Serotonina en la Membrana Plasmática/efectos de los fármacosRESUMEN
The valine side chains in the crystal structure of the title compound [systematic name: 2-(2-ammonio-3-methylbutanamido)-3-hydroxypropanoate trihydrate], C8H16N2O4.3H2O, stack along an a axis of 4.77 A to form hydrophobic columns surrounded by remarkable water/hydroxyl shells. The peptide main chains are connected by hydrogen bonds in two-dimensional layers. The peptide molecules in each layer are related only by translation, and generate a very rare pattern. This is rendered possible through the formation of the shortest C(alpha)-H...O(carboxylate) interaction ever recorded.