Rodriguez Rodrigo A, Pan Po-Shen, Pan Chung-Mao, Ravula Suchitra, Lapera Stephanie, Singh Erinprit K, Styers Thomas J, Brown Joseph D, Cajica Julia, Parry Emily, Otrubova Katerina, McAlpine Shelli R
Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182-1030, USA.
J Org Chem. 2007 Mar 16;72(6):1980-2002. doi: 10.1021/jo061830j. Epub 2007 Feb 22.
We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.
我们报道了34种第二代Sansalvamide A衍生物的合成。Sansalvamide A衍生物具有独特的抗癌特性，可靶向多种癌症，包括结肠癌、胰腺癌、乳腺癌、前列腺癌和黑色素瘤。作为新型模板，本文所述的衍生物探讨了立体化学、酰胺键几何结构、跨环氢键和极性对抗肿瘤效力的作用。测试这些衍生物对多种癌细胞系的化疗活性将提供明确的结构基序，并确定对细胞毒性重要的构象空间。所呈现的34种化合物分为六个系列，其中五个系列涉及在大环的五个位置中的每个位置插入D-氨基酸并结合四种结构特征。第六个系列涉及在大环核心周围每个位置都带有N-甲基的所有L-氨基酸和所有D-氨基酸衍生物之间的比较。与D-氨基酸一起探索的四种结构特征包括N-甲基氨基酸、芳香族氨基酸、极性氨基酸和疏水烷基氨基酸。
