New 10-substituted derivatives of 3,6-diazaphenothiazine, containing the triple bond\nlinker terminated with tertiary cyclic and acyclic amine groups, were synthesized and screened\nfor their anticancer action. The compounds exhibited varied anticancer activities against human\nglioblastoma SNB-19, melanoma C-32, and breast cancer MDA-MB231 cell lines, depending on\nthe nature of the substituents. The most active 3,6-diazaphenothiazine, 4, was the derivative\nwith the N,N-diethylamino-2-butynyl substituent against glioblastoma SNB-19, and was ten times\nmore potent than cisplatin. For this compound, the expression of H3, TP53, CDKN1A, BCL-2,\nand BAX genes was detected by the RT-qPCR method. The gene expression ratio BAX/BCL-2\nindicated the induction of mitochondrial apoptosis in cancer cell lines. The transformation of\nthe propynyl substituent into amino-2-butynyl can be a method applicable to the search for more\nanticancer-active azaphenothiazines.
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