Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznanskiego 8, 61-614 Poznan, Poland.
Centre for Advanced Technology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 10, 61-614 Poznan, Poland.
Int J Mol Sci. 2023 May 19;24(10):8990. doi: 10.3390/ijms24108990.
Purine scaffolds constitute a starting point for the synthesis of numerous chemotherapeutics used in treating cancer, viruses, parasites, as well as bacterial and fungal infections. In this work, we synthesized a group of guanosine analogues containing an additional five-membered ring and a sulfur atom at the C-9 position. The spectral, photophysical, and biological properties of the synthesized compounds were investigated. The spectroscopic studies revealed that a combination of the thiocarbonyl chromophore and the tricyclic structure of guanine analogues shifts the absorption region above 350 nm, allowing for selective excitation when present in biological systems. Unfortunately, due to the low fluorescence quantum yield, this process cannot be used to monitor the presence of these compounds in cells. The synthesized compounds were evaluated for their effect on the viability of human cervical carcinoma (HeLa) and mouse fibroblast (NIH/3T3) cells. It was found that all of them display anticancer activity. In vitro studies were preceded by in silico ADME and PASS analyses, which confirmed that the designed compounds are promising candidates for anticancer agents.
嘌呤骨架是合成用于治疗癌症、病毒、寄生虫以及细菌和真菌感染的许多化疗药物的起点。在这项工作中，我们合成了一组含有额外的五元环和 C-9 位硫原子的鸟嘌呤类似物。研究了合成化合物的光谱、光物理和生物学性质。光谱研究表明，硫羰基生色团和鸟嘌呤类似物的三环结构的组合将吸收区域移动到 350nm 以上，允许在生物系统中进行选择性激发。不幸的是，由于荧光量子产率低，因此不能将此过程用于监测细胞中这些化合物的存在。评估了合成化合物对人宫颈癌（HeLa）和小鼠成纤维细胞（NIH/3T3）细胞活力的影响。结果发现，它们均具有抗癌活性。在体外研究之前，进行了 ADME 和 PASS 分析的计算分析，这证实了所设计的化合物是有前途的抗癌药物候选物。
