Busca Virtual De Compostos Bioativos: Conceitos E Aplicações

Abstract

VIRTUAL SCREENING OF BIOACTIVE COMPOUNDS: CONCEPTS AND APLICATIONS. The search and use of bioactive compounds for different applications have been investigated, since ancient time. Virtual screening (VS) has emerged as alternative methodological approach to the Combinatory Chemistry and High-Throughput Screening (HTS) in identifying novel drug candidates. In VS, only compounds that are selected applying different computational tools to huge virtual libraries of compounds are further tested in vitro. However, the effective use of VS model applications have some challenges such as the inherent complexity of the ligand-receptor interactions as well as by other factors such as ligand and receptor multiple conformations and also ligand metabolic stabilities and toxicities. Altogether these difficulties are hardly overcome using only one computational tool. Therefore, in the literature, it has been suggested to apply a sequence of different filters, such as filters that select compounds through similarity, pharmacophore and docking. In this review, we describe the advantages, limitations and examples of recent successful applications of some of these filters, including drug-like properties, structural properties, 2D similarity, pharmacophore, shape and docking filters. Moreover, we present the main steps involved in the preparation of virtual libraries of compounds that can be used in the VS.

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

“…Table 12 shows that they have good absorption or permeability [ 24 ]. The pIC 50 values (nM) were predicted for the selected molecules, see Table 13 , according to the equations of Table 4 , demonstrating acceptable values.…”

Síntese, atividade antifúngica e docking molecular de derivados do eugenol

“…Entretanto, a trajetória desde a descoberta de uma molécula promissora até a sua aplicação como produto farmacêutico é bastante longa e conta com alguns entraves, o que tem fomentado uma intensa busca por métodos alternativos que contornem estas dificuldades, destacando-se os métodos in silico [23,24]. No geral, um método in silico bastante empregado para esta finalidade é o docking molecular [25], uma vez que permite conjecturar sobre as possíveis interações que podem ser estabelecidas entre o candidato a fármaco e a biomolécula em questão, possibilitando uma melhor compreensão de suas propriedades farmacodinâmicas e fornecendo informações úteis para a condução de modificações estruturais futuras [26,27].…”

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

“…The CADD of new potential ligands that show biological activity or affinity toward AD targets is very promising, as reviewed recently . Nevertheless, few of these reports are focused on the mechanism of action, nor do they consider the possibility of alternative mechanisms that occur between these ligands and the corresponding targets.…”

“…[1,8,23,24] The CADD of new potentiall igands that show biological activity or affinity toward AD targets is very promising,a sr eviewedr ecently. [25][26][27][28] Nevertheless, few of these reports are focused on the mechanism of action,n or do they consider the possibility of alternative mechanisms that occur betweent hese ligandsa nd the corresponding targets. We emphasize that with the term alternative mechanism we mean that the mechanism happensa sc onsequence of al igand binding to ad istinct site, and not to the orthosteric binding site (traditionalm echanism).…”