Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phayathai Road, Wangmai, Patumwan, Bangkok 10330, Thailand.
Molecules. 2021 Feb 15;26(4):1028. doi: 10.3390/molecules26041028.
Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines-HCT116 and SW620. and which are the derivatives containing -hydroxyphenyl substituents exhibited the highest activity with IC against both cell lines in the range of 20-27 µM, which is comparable to the IC of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative . Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, "CaCit- NPs" were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of from the synthesised CaCit- NPs is pH-responsive, and could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.
合成了 12 种双胍衍生的 1,3,5-三嗪衍生物，这是一类很有前途的抗癌药物，并对其进行了评估，以研究它们对两种结直肠癌细胞系（HCT116 和 SW620）的抗癌活性。含有 - 羟基苯基取代基的衍生物表现出最高的活性，对两种细胞系的 IC 均在 20-27 µM 范围内，与顺铂参考物的 IC 相当。此外，还研究了柠檬酸钙纳米粒子（CaCit NPs）作为药物传递系统平台在选定的 1,3,5-三嗪衍生物上的潜在用途。条件优化表明，柠檬酸根离子的来源和反应时间对颗粒的形态、大小和载药量有显著影响。在优化条件下，成功合成了尺寸为 148 ± 23nm 且载药量高达 16.3%的“CaCit-NPs”。此外，发现从合成的 CaCit-NPs 中释放出的呈 pH 响应性，并且可以在酸性癌症环境下控制释放。本研究的知识对于进一步开发基于 1,3,5-三嗪的抗癌药物具有感知意义，并为将来在 CaCit NPs 中加入其他药物提供了平台。
