10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
KAUST DepartmentAdvanced Membranes and Porous Materials Research Center
Online Publication Date2019-07-16
Print Publication Date2019-01
Permanent link to this recordhttp://hdl.handle.net/10754/656498
MetadataShow full item record
Abstract10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced 1H and 13C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine).
CitationMorak-Młodawska, B., Pluta, K., Latocha, M., Jeleń, M., Kuśmierz, D., Suwińska, K., … Jurzak, M. (2019). 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 1298–1306. doi:10.1080/14756366.2019.1639695
SponsorsThe work was supported by the Medical University of Silesia [grant KNW-1–072/K/8/O].
PublisherTaylor and Francis Ltd
RelationsIs Supplemented By:
Morak-Młodawska, B., Pluta, K., Małgorzata Latocha, Małgorzata Jeleń, Kuśmierz, D., Suwińska, K., Shkurenko, A., Czuba, Z., & Jurzak, M. (2019). 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents. Taylor & Francis. https://doi.org/10.6084/M9.FIGSHARE.8874593.V1. DOI: 10.6084/m9.figshare.8874593.v1 Handle: 10754/664763
Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.