Applications of 2D Descriptors in Drug Design: A DRAGON Tale

Abstract

In order to minimize expensive drug failures, is essential to determine potential activity, toxicity and ADME problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening, identification of potential drug is advisable even before synthesis using computational techniques such as QSAR modeling. A great number of in silico approaches to activity/toxicity prediction have been described in the literature, using molecular 0D, 1D, 2D and 3D descriptors. Also these descriptors have been implemented in available computational tools such as DRAGON, SYBYL and CODESSA for it easy use. However, many of them only have been used to explain a few prediction problems. This review attempts to summarize present knowledge related to the computational biological activity prediction based in 2D molecular descriptors implemented in the DRAGON software. These applications rely on new computational techniques such as virtual combinatorial synthesis, virtual computational screening or inverse. Several topological molecular descriptors applications are described, ranging from simple topological indices to topological indices derived from matrices weighted with atomic and bond properties. Their advantages, limitations and its possibilities in drug design are also discussed.

Estudos de QSAR 2D baseados em descritores topológicos e fragmentos moleculares para uma série de derivados azólicos ativos contra Candida albicans

“…impedimentos estéricos), enquanto descritores relacionados com lipofilicidade (nX e MLOGP) têm contribuição positiva (Figura 4). 38,39 É importante ressaltar que outros fatores além da interação ligante-macromolécula influenciam os valores de CIM 80 , portanto, é razoável supor que a contribuição positiva observada no gráfico de vetor de regressão reflita Outra característica importante para atividade antifúngica é a presença de anéis de 5 membros (nR05), representados nesse conjunto de dados pelos anéis triazolona ou triazol, este último comum a todas as moléculas do conjunto de dados. Por outro lado, moléculas potentes (pCIM 80 > 2,0) apresentam anel triazolona, enquanto o mesmo não é observado para moléculas com baixa atividade antifúngica (pCIM 80 < 0,99).…”

Structural Requirements for some 3-amino-N-substituted-4-(substituted phenyl) Butanamides as Dipeptidyl Peptidase-IV Inhibitors Using 3D-QSAR and Molecular Docking Approaches

“…The quantitative structure activity relationship (QSAR) study correlates structural features of compounds with their biological activity/toxicity/other physicochemical properties through the utilization of several descriptors [8] . Descriptors are numerical representations of molecular properties defining electronic, topological, physicochemical and special features of the molecules.…”

Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies

“…In the end QSAR studies were performed with: ten compounds with anti-HCC activity (1b, 1d, 1j, 1s, 1t, 2f, 2g, 2j, 2l and 2m) and 16 with hepatotoxic activity (1b, 1e, 1i, 1j, 1n, 1o, 1p, 1q, 1r, 1s, 1t, 2a, 2b, 2d, 2l and 2n). Then, a total of 1664 molecular descriptors were calculated for each of the selected compound, using the E-Dragon software [21,22]. The descriptors were separated in 4 categories: molecular properties (43), 1D (322), 2D (578) and 3D (721).…”