Raymond and Beverly Sackler Faculty of Exact Sciences, School of Chemistry, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Oncology-Pathology, Karolinska Institute, SE-171 64 Solna, Sweden.
Mar Drugs. 2022 Apr 13;20(4):265. doi: 10.3390/md20040265.
A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge . Seventeen of the compounds, , are new, while six, , were previously characterized from the same sponge. Some of the new acetylene-3-hydroxy alkanes , , , , were tested for selective cytotoxicity in non-small cell lung carcinoma (NSCLC) cells over WI-38 normal diploid lung fibroblasts. Compound , presented clear tumor selective activity while, and , showed selectivity at lower doses and and , were not active towards NSCLC cells at all. The earlier reported selective cytotoxicity of some acetylene-3-hydroxy alkanes ( and ), in NSCLC cells and/or other tumor cell types were also confirmed for , and . To further study the structure activity relationships (SAR) of this group of compounds, we synthesized several derivatives of acetylene-3-hydroxy alkanes, -, -, -, -, -, -, -, -, -, -, -, -, - and -, along with other 3-substituted derivatives, -, -, -, -, - and -, and assessed their cytotoxic activity against NSCLC cells and diploid fibroblasts. SAR studies revealed that the alcohol moiety at position 3 and its absolute configuration both were essential for the tumor cell line selective activity while for its cytotoxic magnitude the alkyl chain length and branching were of less significance.
从加勒比海海绵中分离出了一系列二十三种直链和支链单乙炔脂质。其中十七种化合物、、为新化合物，而六种化合物、、之前已从同一种海绵中鉴定出来。一些新的乙炔-3-羟基烷烃、、、、在非小细胞肺癌（NSCLC）细胞中进行了选择性细胞毒性测试，与 WI-38 正常二倍体肺成纤维细胞相比。化合物、表现出明显的肿瘤选择性活性，而、和、在较低剂量下表现出选择性，而、则对 NSCLC 细胞完全没有活性。先前报道的一些乙炔-3-羟基烷烃（和）在 NSCLC 细胞和/或其他肿瘤细胞类型中的选择性细胞毒性也得到了证实，、和。为了进一步研究这组化合物的结构活性关系（SAR），我们合成了几种乙炔-3-羟基烷烃的衍生物、-、-、-、-、-、-、-、-、-、-、-、-、-、-、-、-、-和-，以及其他 3-取代衍生物、-、-、-、-和-，并评估了它们对 NSCLC 细胞和二倍体成纤维细胞的细胞毒性活性。SAR 研究表明，位置 3 的醇部分及其绝对构型对于肿瘤细胞系的选择性活性都是必不可少的，而对于其细胞毒性大小，烷基链长度和支化程度的重要性较小。
