Abstract
Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.
Keywords: Cancer, metastasis, QSAR, drug design, migrastatin, macrolide, inhibitors, invasion, migration, isomigrastatin analogs, correlation coefficients, anticancer activity
Medicinal Chemistry
Title: Quantitative Structure-Activity Studies on a Series of Migrastatin Analogs as Inhibitors of Cancer Cell Metastasis
Volume: 7 Issue: 3
Author(s): Ricardo N. Santos, Rafael V. C. Guido, Glaucius Oliva, Luiz C. Dias and Adriano D. Andricopulo
Affiliation:
Keywords: Cancer, metastasis, QSAR, drug design, migrastatin, macrolide, inhibitors, invasion, migration, isomigrastatin analogs, correlation coefficients, anticancer activity
Abstract: Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.
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Cite this article as:
N. Santos Ricardo, V. C. Guido Rafael, Oliva Glaucius, C. Dias Luiz and D. Andricopulo Adriano, Quantitative Structure-Activity Studies on a Series of Migrastatin Analogs as Inhibitors of Cancer Cell Metastasis, Medicinal Chemistry 2011; 7 (3) . https://dx.doi.org/10.2174/157340611795564240
DOI https://dx.doi.org/10.2174/157340611795564240 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
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