QSAR Models for Prediction of Binding and Inhibitory Properties of [(E)-2-R-vinyl]benzene Derivatives with Therapeutic Effects against Helicobacter pylori.

Sancho Sanz, Javier (Universidad de Zaragoza) ; Galano, Juan J. (Universidad de Zaragoza)

Resumen: The classical Quantitative Structure-Activity Relationship (QSAR as we know them today) emerged in the first half of the 60s with the early works of Hansch and Fujita [1], the Free-Wilson method [2], the subsequent modification made by Ban [3] and the later approaches proposed by Kubinyi [4-10] and Topliss [11]. QSAR, assisted by a wealth of organic synthetic techniques, computer technologies and by the discovery of many potential therapeutic targets, has since become a central tool for chemists, biologists and biochemists in search of improving active compounds to use them as drugs for the treatment of a variety of diseases. Helicobacter pylori (Hp) is a gram-negative bacteria that establishes life-long infections in the gastric mucosa of infected people [12,13]. Nowadays, about 50% of the global population is believed to be infected by Hp, with a lower prevalence in Europe and the United States but much higher in developing countries [14]. The presence of Hp in the human gastric mucosa is related to the development of diseases such as type B gastritis, chronic peptic ulcers and gastric neoplasias on individuals infected by that microorganism.Traditional treatment used worldwide to combat Hp, known as the triple therapy (one proton pump inhibitor together with two wide spectrum antibiotics: clarithromycin and a choice of amoxicillin or metronidazole) [15], has unfortunately lost efficacy due to increased resistances. No new drugs have been developed in recent years to treat Hp infection, but some selective targets (one of them being the protein flavodoxin: Hp-Fld) have been identified [16]. Hp-Fld is an electron carrier essential for Hp viability [17,18] and it has been used in previous works [19,20] as target for the discovery of novel compounds that could be potential drugs against Hp. Four different biological responses (BR) or biological activities were assayed for those novel compounds, which are mainly derived from a common substructure represented in Figure 1. From those data we have gathered a database of 24 congeneric compounds and their respective biological activity values. We describe here two QSAR models for the binding affinity and the therapeutic potency of bactericidal compounds based on the [(E)-2-R-vinyl]benzene scaffold (Figure 1), which will guide the future improvement of Hp-specific bactericides.

Idioma: Inglés

DOI: 10.4172/2161-0444.1000157

Año: 2013

Publicado en: Medicinal Chemistry 4, 1 (2013), 306-12
ISSN: 1573-4064

Factor impacto JCR: 1.387 (2013)

Categ. JCR: CHEMISTRY, MEDICINAL rank: 43 / 58 = 0.741 (2013) - Q3 - T3

Tipo y forma: Article (Published version)

Área (Departamento): Proy. investigación DEA (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)