A series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of several pyrimidine nucleosides was synthesized and evaluated for the in vitro cytotoxicity against human cancer cell lines M-HeLa, MCF-7, PANC-1, PC-3, DU145, SKOV-3, A275, and normal human cell line WI-38. In these TPP-conjugates triphenylphosphonium cation was attached via a tetramethylene chain to the N-3 atom of the heterocycle moiety (uracil, thymine, quinazoline-2,4-dione), which was coupled with the D-ribofuranosyl-1,2,3-triazol-4-yl fragment via methylene or tetramethylene linker. It was shown for the first time that the conjugation of 1,2,3-triazolyl derivatives of uridine, its analogues featuring quinazoline-2,4-dione fragment as well as uracil and thymine derivatives, having propargyl or a 1,2,3-triazolyl substituent at the N-1 atom, with a TPP-butyl cation endowed some of them with cytotoxic activity against human cancer cells. Among all human cancer cell lines used, DU-145 and A375 cells were the most sensitive to these TPP conjugates. At the same time, all tested compounds did not inhibit growth of normal cells WI-38. Propargyl containig TPP-conjugates of uracil 4f, 4j, and thymine 5f showed the highest cytotoxicity with IC₅₀ values in the low micromolar concentration range. The present findings suggest that TPP-conjugates of uracil and thymine derivatives would be promising for further development as an anticancer agent.

合成了一系列嘧啶核苷的1,2,3-三唑基类似物的一系列三苯基phosph（TPP）缀合物，并评估了其对人癌细胞系M-HeLa，MCF-7，PANC-1，PC-3的体外细胞毒性，DU145，SKOV-3，A275和正常人细胞系WI-38。在这些TPP共轭物中，三苯基phosph阳离子通过四亚甲基链连接到杂环部分（尿嘧啶，胸腺嘧啶，喹唑啉-2,4-二酮）的N- 3原子上，并与D-呋喃呋喃糖基1,2,3偶联， 3-三唑-4-基片段通过亚甲基或四亚甲基接头。首次显示尿苷的1,2,3-三唑基衍生物的缀合物，其类似物具有喹唑啉-2,4-二酮片段以及尿嘧啶和胸腺嘧啶衍生物，具有炔丙基或1,2,3在N -1原子上的-三唑基取代基和TPP-丁基阳离子赋予了其中一些对人类癌细胞的细胞毒活性。在所有使用的人类癌细胞系中，DU-145和A375细胞对这些TPP缀合物最敏感。同时，所有测试的化合物均未抑制正常细胞WI-38的生长。尿嘧啶4f，4j和胸腺嘧啶5f的炔丙基TPP结合物对IC _50的细胞毒性最高在低摩尔浓度范围内的数值。目前的发现表明，尿嘧啶和胸腺嘧啶衍生物的TPP-缀合物有望作为抗癌剂进一步发展。