RESUMEN
In view of obtaining some potential antibacterial compounds, we have described synthesis of some chloroaryloxyalkyl imidazole and benzimidazole derivatives. The relevant step in the synthetic sequence was the initial condensation of 4-chloro or 2,4-dichlorophenol with 1, n-dibromoalkanes (n=2, 4, 5) to provide compounds 3a-f in sufficient yields. The subsequent condensation of 3a-f with some imidazole derivatives and benzimidazole afforded products 4a-l and 5a-e in good yields. Some of compounds 4a-l as well as 5a-e were tested in vitro against Salmonella typhi O-901 and Staphylococcus aureus A 15091. Compounds 4a and 4c showed considerable bactericidal activities against tested bacteria. Compound 4b showed significant activity against S. aureus A 15091 but was inactive against S. typhi O-901. Other compounds showed intermediate activities against S. aureus A 15091 but most of them were inactive against S. typhi O-901. Semiempirical AM1 calculations showed that negative electrostatic potentials around oxygen of the phenoxy and nitrogen of the imidazole moieties have direct effect on the antibacterial activity towards S. aureus A 15091. In QSAR analysis, different electronic, topologic, functional groups and physicochemical descriptors were calculated for each molecule and a three parametric equation was found between the logMIC and HOMO energy, hydration energy and number of primary carbon atoms of the molecules.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Bencimidazoles/química , Cloruros/química , Diseño de Fármacos , Imidazoles/química , Relación Estructura-Actividad Cuantitativa , Alquilación , Antibacterianos/química , Bencimidazoles/síntesis química , Modelos Moleculares , Estructura Molecular , Oxidación-ReducciónRESUMEN
We describe the impact of subtype differences on the seroreactivity of linear antigenic epitopes in envelope glycoprotein of HIV-1 isolates from different geographical locations. By computer analysis, we predicted potential antigenic sites of envelope glycoprotein (gp120 and gp4l) of this virus. For this purpose, after fetching sequences of proteins of interest from data banks, values of hydrophilicity, flexibility, accessibility, inverted hydrophobicity, and secondary structure were considered. We identified several potential antigenic epitopes in a B subtype strain of envelope glycoprotein of HIV-1 (IIIB). Solid- phase peptide synthesis methods of Merrifield and Fmoc chemistry were used for synthesizing peptides. These synthetic peptides corresponded mainly to the C2, V3 and CD4 binding sites of gp120 and some parts of the ectodomain of gp41. The reactivity of these peptides was tested by ELISA against different HIV-1-positive sera from different locations in India. For two of these predicted epitopes, the corresponding Indian consensus sequences (LAIERYLKQQLLGWG and DIIGDIRQAHCNISEDKWNET) (subtype C) were also synthesized and their reactivity was tested by ELISA. These peptides also distinguished HIV-1-positive sera of Indians with C subtype infections from sera from HIV-negative subjects.
Asunto(s)
Humanos , Ensayo de Inmunoadsorción Enzimática , Proteína gp120 de Envoltorio del VIH , Proteína gp41 de Envoltorio del VIH , VIH-1 , Inmunogenética , IndiaRESUMEN
We describe the impact of subtype differences on the seroreactivity of linear antigenic epitopes in envelope glycoprotein of HIV-1 isolates from different geographical locations. By computer analysis, we predicted potential antigenic sites of envelope glycoprotein (gp120 and gp4l) of this virus. For this purpose, after fetching sequences of proteins of interest from data banks, values of hydrophilicity, flexibility, accessibility, inverted hydrophobicity, and secondary structure were considered. We identified several potential antigenic epitopes in a B subtype strain of envelope glycoprotein of HIV-1 (IIIB). Solid- phase peptide synthesis methods of Merrifield and Fmoc chemistry were used for synthesizing peptides. These synthetic peptides corresponded mainly to the C2, V3 and CD4 binding sites of gp120 and some parts of the ectodomain of gp41. The reactivity of these peptides was tested by ELISA against different HIV-1-positive sera from different locations in India. For two of these predicted epitopes, the corresponding Indian consensus sequences (LAIERYLKQQLLGWG and DIIGDIRQAHCNISEDKWNET) (subtype C) were also synthesized and their reactivity was tested by ELISA. These peptides also distinguished HIV-1-positive sera of Indians with C subtype infections from sera from HIV-negative subjects.