Fytas Christos, Zoidis Grigoris, Tsotinis Andrew, Fytas George, Khan Mohsin A, Akhtar Samar, Rahman Khondaker M, Thurston David E
School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
Eur J Med Chem. 2015 Mar 26;93:281-90. doi: 10.1016/j.ejmech.2015.02.021. Epub 2015 Feb 16.
Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast cancer, MIA PaCa2 pancreatic cancer, and NCI H1975 non-small cell lung cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 μΜ, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts).
新型1-(2-芳基-2-金刚烷基)哌嗪衍生物已被合成，并在体外对其针对人宫颈癌HeLa细胞、人乳腺癌MDA MB 231细胞、人胰腺癌MIA PaCa2细胞和人非小细胞肺癌NCI H1975细胞的抗肿瘤特性进行了评估。发现母体哌嗪6对HeLa和MDA MB 231肿瘤细胞系表现出一定活性（IC50分别为9.2和8.4 μΜ）。化合物6的哌嗪基NH同时进行苯环C4-氟化和哌啶乙酰化，得到了该系列在上述两种细胞系中活性最高的化合物13（IC50分别为8.4和6.8 μΜ）。值得注意的是，化合物6和13对正常人细胞人脐静脉内皮细胞（HUVEC）和正常人皮肤成纤维细胞（NHDF）的细胞毒性水平显著较低。
