Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives
A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted de...
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MDPI AG
2016-11-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/11/1455 |
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| author | Andrzej Zięba Małgorzata Latocha Aleksander Sochanik Anna Nycz Dariusz Kuśmierz |
| author_facet | Andrzej Zięba Małgorzata Latocha Aleksander Sochanik Anna Nycz Dariusz Kuśmierz |
| author_sort | Andrzej Zięba |
| collection | DOAJ |
| description | A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine) system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines). Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53), apoptosis (BAX, BCL-2), as well as proliferation (H3) were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide. |
| first_indexed | 2024-12-13T02:53:05Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T02:53:05Z |
| publishDate | 2016-11-01 |
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| spelling | doaj.art-a54e0d8b704c4997a70ead973bb7a62d2022-12-22T00:02:01ZengMDPI AGMolecules1420-30492016-11-012111145510.3390/molecules21111455molecules21111455Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine DerivativesAndrzej Zięba0Małgorzata Latocha1Aleksander Sochanik2Anna Nycz3Dariusz Kuśmierz4Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 9, 41-200 Sosnowiec, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeże AK 15, 44-101 Gliwice, PolandDepartment of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 9, 41-200 Sosnowiec, PolandA novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine) system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines). Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53), apoptosis (BAX, BCL-2), as well as proliferation (H3) were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.http://www.mdpi.com/1420-3049/21/11/1455phenothiazineazaphenothiazineanticancercisplatin |
| spellingShingle | Andrzej Zięba Małgorzata Latocha Aleksander Sochanik Anna Nycz Dariusz Kuśmierz Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives Molecules phenothiazine azaphenothiazine anticancer cisplatin |
| title | Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives |
| title_full | Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives |
| title_fullStr | Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives |
| title_full_unstemmed | Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives |
| title_short | Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives |
| title_sort | synthesis and in vitro antiproliferative activity of novel phenyl ring substituted 5 alkyl 12 h quino 3 4 b 1 4 benzothiazine derivatives |
| topic | phenothiazine azaphenothiazine anticancer cisplatin |
| url | http://www.mdpi.com/1420-3049/21/11/1455 |
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