Anticancer activity of newly synthesized azaphenothiazines from NCI's anticancer screening bank.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 2
Abstract
The activity of the newly synthesized azaphenothiazines: tricyclic 10-substituted dipyridothiazines 1-9, pentacyclic 6-substituted diquinothiazines 10-22 and hexacyclic diquinothiazinium salt 23 was tested on 55-60 in vitro cell lines. The cell lines included nine types of cancer: leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer (National Cancer Institute, Bethesda, MD, USA). The features of the chemical substituent at the thiazine nitrogen atom confer the anticancer activity of diquinothiazines 10-23. Unexpectedly, the most active of the dipyridothiazines 1-9 was the unsubstituted compound 1 (the substituent is a hydrogen atom). The most cytotoxic compound was the half-mustard derivative 18. The GI(50) value of this compound was -7.06 (corresponding to 40 ng/ml) when tested on the melanoma cell line SK-MEL-5 and -6.0 - -6.62 using cell lines from various cancers including: leukemia (CCRF-CEM), the MOLT-4 cell line, colon cancer (HCT-116), central nervous system cancer (SNB-75 and SF-295), prostate cancer (PC-3), non-small cell lung cancer (NCI-H460 and HOP-92), ovarian cancer (IGROV1 and OVCAR-4) and breast cancer (MDA-MB-460). The ethylene group in the aminoalkylazaphenothiazines is as a good linker and is similar to the propylene and butylene linkers in aminoalkylphenothiazines. To our knowledge, this is the first demonstration of significant azaphenothiazine anticancer activity.
Authors and Affiliations
Krystian Pluta, Małgorzata Jeleń, Beata Morak-Młodawska, Michał Zimecki, Jolanta Artym, Maja Kocięba
Keywords
Related Articles
- EP ID EP96991
- DOI -
- Views 95
- Downloads 0
Calcium mobilization by the plant estrogen ferutinin does not induce blood platelet aggregation.
Platelet activation is closely associated with an increase in intracellular Ca(2+) concentration. Various compounds including Ca(2+) ionophores are able to trigger platelet aggregation by increasing intracellular Ca(2+)...
Limited applicability of 7-methoxy-4-trifluoromethylcoumarin as a CYP2C9-selective substrate.
Fluorometric substrates selective for various cytochrome P450 isoforms (P450s) have great advantages in in vitro enzyme inhibition and induction studies because they are highly sensitive and suitable for rapid screening....
MDR1 (ABCB1) gene polymorphism C3435T is associated with P-glycoprotein activity in B-cell chronic lymphocytic leukemia.
Functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the MDR1 (ABCB1) gene encoding the xenobiotic transporter P-glycoprotein (P-gp, MDR1, ABCB1) may influence susceptibility to several diseases as well a...
Puerarin inhibits iNOS, COX-2 and CRP expression via suppression of NF-κB activation in LPS-induced RAW264.7 macrophage cells.
Puerarin (7,4'-dihydroxy-8-C-glucosylisoflavone) is the most abundant isoflavone-C-glucoside extracted from Radix puerariae, and it has been used for various medicinal purposes in traditional oriental medicine for thousa...
Effects of selective sigma receptor ligands on glucocorticoid receptor-mediated gene transcription in LMCAT cells.
It has been shown previously that sigma receptor agonists reveal potential antidepressant activity in experimental models. Moreover, some data indicate sigma receptor contribution to stress-induced responses (e.g., condi...