Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 4a Chodzki Str., 20-093 Lublin, Poland.
Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1 Street, 15-089 Bialystok, Poland.
Molecules. 2022 Oct 17;27(20):6977. doi: 10.3390/molecules27206977.
Based on the results of previous work, we designed and synthesized 1,3,4-thiadiazole derivatives. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and a normal cell line (fibroblasts). The results showed that all compounds displayed weak anticancer activity towards two breast cancer lines: an estrogen-dependent cell line (MCF-7) and an estrogen-independent cell line (MDA-MB-231). The compound most active towards MCF-7 breast cancer cells was SCT-4, which decreased DNA biosynthesis to 70% ± 3 at 100 µM. The mechanism of the anticancer action of 1,3,4-thiadiazole was also investigated. We choose a set of the most investigated proteins, which are attractive anticancer targets. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds but the most likely mechanism of action for the new compounds is connected with the activity of caspase 8.
基于先前工作的结果，我们设计并合成了 1,3,4-噻二唑衍生物。然后，通过 MCF-7 和 MDA-MB-231 乳腺癌细胞和正常细胞系（成纤维细胞）的生物学研究来测定所得化合物的细胞毒性活性。结果表明，所有化合物对两种乳腺癌系（依赖雌激素的 MCF-7 细胞系和非依赖雌激素的 MDA-MB-231 细胞系）均显示出较弱的抗癌活性。对 MCF-7 乳腺癌细胞最活跃的化合物是 SCT-4，其在 100µM 时将 DNA 生物合成降低至 70%±3。还研究了 1,3,4-噻二唑的抗癌作用机制。我们选择了一组最受关注的蛋白质，这些蛋白质是有吸引力的抗癌靶标。计算机研究表明，合成化合物可能具有多靶作用模式，但新化合物的最可能作用机制与半胱天冬酶 8 的活性有关。
