Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design.
Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design.
复制标题
使用多变量分析和计算辅助药物设计研究细胞毒性新木脂素衍生物的结构-活性关系。
DOI：
10.1016/j.bmcl.2020.127349
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发表时间：
2020
影响因子：
2.7
通讯作者：
De Sousa FS
中科院分区：
文献类型：
--
作者：
De Sousa FS
脱氢丁香酚B和五种相关的天然新木脂素是从巴西植物Nectandra leucantha中分离得到的。这些化合物中的三种显示出对鼠（B16 F10）和人（A2058）黑素瘤细胞有活性，但对人成纤维细胞（T75）无毒。这些结果刺激了一系列23个半合成衍生物的制备，以探索结构-活性关系，并研究这些衍生物对B16 F10和A2058细胞系的生物学潜力。这些结构相关的新木脂素衍生物进行了分析，多元统计和机器学习，这表明，最重要的特征是与它们的三维结构，主要是，取代基上的新木脂素骨架。结果表明，羟基或烷氧基在位置3，4和5（与适当的侧链）的存在下，促进了电和电荷密度的增加，这似乎是重要的生物活性对小鼠（B16 F10）和人类（A2058）黑色素瘤细胞。
Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant speciesNectandra 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.
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影响因子：
6.7
作者：
Ferreira, Daiane D.;Sousa, Fernanda S.;Tempone, Andre G.
通讯作者：
Tempone, Andre G.
影响因子：
5.1
作者：
da Costa-Silva TA;Grecco SS;de Sousa FS;Lago JH;Martins EG;Terrazas CA;Varikuti S;Owens KL;Beverley SM;Satoskar AR;Tempone AG
通讯作者：
Tempone AG
影响因子：
3.8
作者：
de Sousa, Fernanda S.;Grecco, Simone S.;Lago, Joao Henrique G.
通讯作者：
Lago, Joao Henrique G.
影响因子：
2.7
作者：
Chagas-Paula, Daniela Aparecida;Oliveira, Tiago Branquinho;Da Costa, Fernando Batista
通讯作者：
Da Costa, Fernando Batista
影响因子：
7.4
作者：
Lo YC;Rensi SE;Torng W;Altman RB
通讯作者：
Altman RB