a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
b Division of Pharmacology , Meikai University School of Dentistry , Sakado , Saitama , Japan.
J Enzyme Inhib Med Chem. 2016;31(sup3):105-109. doi: 10.1080/14756366.2016.1209495. Epub 2016 Jul 19.
A series of Mannich bases having piperidine moiety were reacted with 2-mercaptoethanol, leading to 1-aryl-3-piperidine-4-yl-1-propanone hydrochlorides. The cytotoxicity and carbonic anhydrase inhibitory activities of these new compounds were evaluated. Among the compounds, only one derivative, nitro substituent bearing EU9, showed an effective cytotoxicity, although weak tumor specificity against human oral malignant versus nonmalignant cells. The compound induced apoptosis in HSC-2 oral squamous cell carcinoma cells, but not in human gingival fibroblast. Chemical modifications of this lead are thus necessary to further investigate it as a drug candidate and to obtain compounds with a better activity profile.
一系列含哌啶部分的曼尼希碱与 2-巯基乙醇反应,得到 1-芳基-3-哌啶-4-基-1-丙酮盐酸盐。评价了这些新化合物的细胞毒性和碳酸酐酶抑制活性。在这些化合物中,只有含有硝基取代基的 EU9 衍生物表现出有效的细胞毒性,尽管对人口腔恶性与非恶性细胞的肿瘤特异性较弱。该化合物在 HSC-2 口腔鳞状细胞癌细胞中诱导细胞凋亡,但在人牙龈成纤维细胞中不诱导细胞凋亡。因此,需要对该先导化合物进行化学修饰,以进一步将其作为候选药物进行研究,并获得具有更好活性谱的化合物。