Structure-activity relationships of antifilarial antimycin analogs: a multivariate pattern recognition study

Abstract

The structure-activity relationships of a series of novel antifilarial antimycin A1 analogues have been investigated by using computational chemistry and multivariate statistical techniques. The physiochemical descriptors calculated in this way contained information which was useful in the classification of compounds according to their in vitro antifilarial activity. This approach generated a 53 parameter descriptor set, which was reduced with a multivariate pattern recognition package, ARTHUR. Regression analysis of the reduced set yielded several statistically significant regression equations; e.g.-log in vitro activity = 0.017 mp + 0.65 log P - 0.81ESDL10-7.33 (R = 0.9). With use of this equation, it was possible to make predictions for further untested analogues. The analysis indicated that membrane or lipid solubility is an important determinant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake.

Exploratory Data Analysis with Latent Subspace Models

“…This deviation is highly contributing to the variance in the first LV and the reason for it should be investigated. Two of these compounds, K17 and K18, were catalogued as outliers by (34), where the authors stated that "Chemically, these compounds are distinct from the bulk of the training set in that they have an n-alkyl side chain as opposed to a side chain of the phenoxy ether type". Since the four compounds present an abnormally low score in the first LV, typically the analyst may interpret the coefficients of that LV to try to explain this abnormality.…”

Seleção de variáveis em QSAR

“…A busca sistemática consiste em combinar as m variáveis disponíveis de forma a construir e analisar todos as possí-veis equações de regressão com k variáveis e, a partir daí, selecionar as melhores. Por exemplo, desejando-se saber qual a melhor regressão que pode ser obtida com k = 3, 15 , devem-se construir equações utilizando-se todas as possíveis combinações não repetidas das quinze variáveis, três a três. Ou seja,…”

“…Seja a matriz de Selwood 15 , que apresenta n = 31 e m = 53. Sabendo-se que o número de possíveis equações de regressão com k variáveis é dado pela fórmula m!/[k!(m-k)!…”

“…Alguns algoritmos pseudo-evolucionários, que não executam cruzamento entre os indivíduos e que utilizam combinação de AG e busca sistemática 16,27,28 , também vêm apresentando bons resultados na solução da matriz de Selwood 15 .…”

Inhibition of electron transport of rat liver mitochondria by unnatural (‐)‐antimycin A3

“…The structural aspects ofantimycin A needed for inhibitory ~,ctivity are fairly well understood [3][4][5][6], the phenolk: hydroxy group of the salicylic acid moiety of the antimycin molecule is necessary for its inhibitory activity, but the dilactone ring moiety may be replaced by other hydrophobic groups such as long alkyl chain. The stereochemical aspects of antimycin A that govern its inhibitory activity are not known.…”