Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 11, Issue 4, 2011

As a continuation of Part I, herein Garry Buettner [1] addressed the critical role of manganese superoxide dismutase, MnSOD - the enzyme that we cannot live without. MnSOD is a central player in the redox biology of cells and tissues [1]. It is critical for establishing the appropriate balance in redox circuitry of the mitochondria. Thus, there has been an increasing demand to develop powerful SOD mimics. In the studies where Read More

Cationic Mn(III) N-alkylpyridyl (MnTalkyl-2(or 3)-PyP5+) and N, N'-dialkylimidazolylporphyrins (MnTDalkyl-2-ImP5+) have been regarded as the most powerful SOD mimics/peroxynitrite scavengers - i. e. antioxidants. The ethyl-, MnTE-2-PyP5+ (AEOL10113), and hexylpyridyl-, MnTnHex-2-PyP5+ and diethylimidazolylporphyrin, MnTDE-2-ImP5+ (AEOL10150) have been mostly studied in vitro and in vivo. Given the in vivo abundance Read More

Superoxide dismutases (SOD) are considered to be antioxidant enzymes. This view came about because its substrate, superoxide, is a free radical; in the era of their discovery, 1960's - 1970's, the general mindset was that free radicals in biology must be damaging. Indeed SOD blunts the cascade of oxidations initiated by superoxide. However in the late 1970's it was observed that cancer cells that have low activity of the Read More

Nitroxides are low molecular weight (150-400 Da) superoxide dismutase mimics that exhibit antioxidant, radical scavenging, and radioprotective activity. Additionally, the paramagnetic nature of nitroxides makes them viable as both spin probes for electron paramagnetic resonance imaging as well as contrast agents for magnetic resonance imaging. These imaging techniques enable in vivo monitoring of nitroxide metabolis Read More

Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusin Read More

The nitrone compound PBN, α-phenyl-tert-butylnitrone, and closely related nitrones have anti-cancer activity in several experimental cancer models. The three experimental models most extensively studied include A) the rat choline deficiency liver cancer model, B) the rat C6 glioma model and C) the mouse APCMin/+ colon cancer model. The two PBN-nitrones mostly studied are PBN and a PBN derivative 2,4-disulfop Read More

We report here an investigation that focuses on the organ distribution of metal complexes that are chelated by the amphipolar corrole whose macrocycle is decorated by two sulphonic acid head groups, which are emerging potential therapeutics against cancer (the cytotoxic Ga chelate) and diseases that are characterized by excessive production of ROS and RNS (the cytoprotective Mn and Fe derivatives). We show that t Read More

Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that ha Read More

The medicinal properties of garlic (Allium sativum) have been well known and widely used since historical times. Garlic compounds have received increasing attention during the last few years due to their cancer chemopreventive properties. The anti-cancer activity of garlic-derived organosulfur compounds (OSCs) are extensively reported in many cancers but only a few in the pediatric tumor neuroblastoma, which Read More