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 108
- Downloads 0
Optimization of lidocaine application in tumescent local anesthesia.
Tumescent local anesthesia is based upon the infusion of large volumes of neutralized anesthetic solutions, mainly lidocaine, at very low concentrations. This results in the paralysis of sensory nerve endings and minute...
Effects of melatonin in a place preference conditioning depend on the time of administration.
A conditioned place preference paradigm was used to assess potential rewarding properties of melatonin. The conditioning with melatonin was carried out at two periods of the 12-h light/dark cycle: in the morning (08.30-1...
Tumor anti-initiating activity of some novel 3,4-dihydropyrimidinones.
Halting the tumor initiation process by targeting the inhibition of the carcinogens metabolic activators (CYP), the induction of the carcinogen detoxification enzymes (glutathione-S-transferases, GSTs), and the induction...
Ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel blocker) elevates the threshold for maximal electroshock-induced tonic seizures in mice.
Background: The aim of this study was to determine the effect of ivabradine (a hyperpolarization activated cyclic nucleotide-gated channel (HCN) blocker) on the threshold for maximal electroshock (MEST)-induced tonic sei...
Endothelial mitochondria as a possible target for potassium channel modulators
Variety of ion channels is present in plasma membrane of endothelial cells. These include the potassium channels such as Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels, voltage-dependent K(+) channels...