Santra Sougata, Sharapov Ainur D, Fatykhov Ramil F, Potapova Anastasya P, Khalymbadzha Igor A, Valieva Maria I, Kopchuk Dmitry S, Zyryanov Grigory V, Bunev Alexander S, Melekhin Vsevolod V, Gaviko Vasiliy S, Zonov Andrey A
Department of Organic and Biomolecular Chemistry, Ural Federal University, Mira 19, 620002 Ekaterinburg, Russia.
Medicinal Chemistry Center, Togliatti State University, Belorusskaya 14, 445020 Togliatti, Russia.
Pharmaceuticals (Basel). 2023 Mar 7;16(3):403. doi: 10.3390/ph16030403.
A total of 21 novel xanthone and acridone derivatives were synthesized using the reactions of 1,2,4-triazine derivatives with 1-hydroxy-3-methoxy-10-methylacridone, 1,3-dimethoxy-, and 1,3-dihydroxanthone, followed by optional dihydrotiazine ring aromatization. The synthesized compounds were evaluated for their anticancer activity against colorectal cancer HCT116, glioblastoma A-172, breast cancer Hs578T, and human embryonic kidney HEK-293 tumor cell lines. Five compounds (, , , , and ) displayed good in vitro antiproliferative activities against these cancer cell lines. Compounds and demonstrated low toxicity for normal human embryonic kidney (HEK-293) cells, which determines the possibility of further development of these compounds as anticancer agents. Annexin V assay demonstrated that compound activates apoptotic mechanisms and inhibits proliferation in glioblastoma cells.
使用1,2,4 - 三嗪衍生物与1 - 羟基 - 3 - 甲氧基 - 10 - 甲基吖啶酮、1,3 - 二甲氧基和1,3 - 二羟基氧杂蒽的反应，随后进行任选的二氢噻嗪环芳构化，总共合成了21种新型氧杂蒽和吖啶酮衍生物。对合成的化合物针对结肠直肠癌HCT116、胶质母细胞瘤A - 172、乳腺癌Hs578T和人胚肾HEK - 293肿瘤细胞系进行了抗癌活性评估。五种化合物（、、、和）对这些癌细胞系表现出良好的体外抗增殖活性。化合物和对正常人胚肾（HEK - 293）细胞显示出低毒性，这决定了将这些化合物进一步开发为抗癌剂的可能性。膜联蛋白V测定表明化合物激活胶质母细胞瘤细胞中的凋亡机制并抑制其增殖。
