Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle (Saale), Germany.
University Clinic for Internal Medicine IV, Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
Int J Mol Sci. 2023 Jun 27;24(13):10695. doi: 10.3390/ijms241310695.
1,5-Diazacyclooctane was prepared by a simple synthetic sequence and coupled to pentacyclic triterpenoic acids oleanolic acid, ursolic acid, betulinic acid, platanic acid, and asiatic acid; these amides were activated with oxalyl chloride and reacted with rhodamine B or rhodamine 101 to yield conjugates. The conjugates were screened in SRB assays with various human breast cancer cell lines (MDA-MB-231, HS578T, MCF-7, and T47D) and found to exert cytotoxic activity even at a low concentration. Therefore, for an asiatic acid rhodamine 101 conjugate (28), an IC = 0.60 nM was determined and found to induce apoptosis in MDA-MB-231 and HS578T cells. Extra experiments showed the compound to act as a mitocan and to induce inhibition of proliferation or growth arrest in MDA-MB-231 cells at lower doses followed by an induction of apoptosis at higher doses. Furthermore, differential responses to proliferation inhibition and apoptosis induction may explain differential sensitivity of mammary cell lines to compound 28.
1,5-二氮杂环辛烷通过简单的合成序列制备，并与五环三萜酸齐墩果酸、熊果酸、白桦脂酸、角鲨烷和虎杖酸偶联；这些酰胺用草酰氯激活，然后与若丹明 B 或若丹明 101 反应生成缀合物。这些缀合物在 SRB 测定中与各种人乳腺癌细胞系（MDA-MB-231、HS578T、MCF-7 和 T47D）进行筛选，发现即使在低浓度下也具有细胞毒性活性。因此，对于虎杖酸若丹明 101 缀合物（28），确定 IC=0.60 nM，并发现其在 MDA-MB-231 和 HS578T 细胞中诱导细胞凋亡。额外的实验表明，该化合物作为一种线粒体抑制剂，在较低剂量下抑制 MDA-MB-231 细胞的增殖或生长停滞，然后在较高剂量下诱导细胞凋亡。此外，对增殖抑制和凋亡诱导的不同反应可以解释乳腺细胞系对化合物 28 的不同敏感性。
