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Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design
Affiliation:2. Laboratório de Aquacultura de Espécies Tropicais, Instituto Federal de Educação, Ciência e Tecnologia do Pará – IFPA Castanhal, 68740-970 Castanhal, PA, Brazil;4. Laboratório de Bioquímica Funcional, Universidade Federal do Rio Grande, CP 474, 96200-970 Rio Grande, RS, Brazil;6. Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil;1. Departamento de Farmácia, Universidade Estadual de Maringá, Maringá, Paraná, Brazil;2. Departamento de Química, Universidade Estadual de Maringá, Maringá, Paraná, Brazil;3. Departamento de Biologia, Universidade Estadual de Maringá, Maringá, Paraná, Brazil;4. Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
Abstract:Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant species Nectandra leucantha. Three of these compounds were shown to be active against murine (B16F10) and human (A2058) melanoma cells but non-toxic to human fibroblasts (T75). These results stimulated the preparation of a series of 23 semi-synthetic derivatives in order to explore structure-activity relationships and study the biological potential of these derivatives against B16F10 and A2058 cell lines. These structurally-related neolignan derivatives were analyzed by multivariate statistics and machine learning, which indicated that the most important characteristics were related to their three-dimensional structure and, mainly, to the substituents on the neolignan skeleton. The results suggested that the presence of hydroxyl or alkoxyl groups at positions 3, 4 and 5 (with appropriate sidechains) promoted an increase in electropological and charge density, which seem to be important for biological activity against murine (B16F10) and human (A2058) melanoma cells.
Keywords:Neolignans  Semi-synthetic derivatives  Cytotoxic  B16F10  A2058  Multivariate analysis
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