Current Topics in Medicinal Chemistry - Volume 8, Issue 6, 2008

Mother nature often provides scientists with new and innovative ideas. One perfect example is enediynes which have now become the core of research in cancer therapeutics. Enediynes are a group of cyclic natural molecules that consist of at least two triple bonds separated by a double bond in conjugation. These products of bacterial origin were first isolated in 1960s and have drawn special attention since mid-eighties f Read More

Of the commonly recognized structural elements within nucleic acids, bulges are among the least developed as targets for small molecules. Bulges in DNA and RNA have been linked to biomolecular processes involved in numerous diseases, thus probes with affinity for these targets would be of considerable utility to chemical biologists and medicinal chemists. Despite such opportunity, there is a dearth of small molecules availabl Read More

The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that a Read More

The concept of photoswitchable enediynes, which are stable in the dark but undergo efficient cycloaromatization reaction to produce p-benzyne diradical after irradiation with light of an appropriate wavelength, is discussed. Two novel methods for the generation of reactive enediyne compounds from thermally stable precursors have been developed. In the first approach, one of the triple bonds of cyclodeca-3-ene-1,5 Read More

It has been shown that the enediyne anticancer antibiotics e.g., calicheamicin, neocarzinostatin and others cleave DNA via the putative intermediate 1,4-diradical formed in the Bergmann cyclization and are thus useful for cancer chemotherapy. The pharmacological activity of these drugs is based, in general, on the activation of the pharmacophore and the subsequent cyclization leading to the formation of a radical, Read More

Enediynes continue to fascinate scientists working in various domains because of their structural complexity and fascinating biological mode of action. They represent a masterpiece of nature's ingenuity. Besides the warhead which is the enediyne moiety, these molecules are equipped with a locking device, a delivery system and a chemical trigger for activation. Upon triggering, the molecules become active and undergo a t Read More

The pituitary is the preeminent gland of the body, synthesizing and releasing key hormones including growth hormone, thyroid-stimulating hormone, prolactin, luteinizing hormone, follicle-stimulating hormone and adrenocorticotropic hormone. The secretion of these hormones is regulated by the hypothalamus via the hypothalamus-hypophyseal portal veins. The target organ of adrenocorticotropic hormone is the Read More

Antagonists of the corticotropin releasing factor (CRF or CRH) receptor have shown promise for the treatment of anxiety, depression, and irritable bowel syndrome. In the present article, medicinal chemistry developments surrounding small molecule CRF receptor antagonists are reviewed, focusing on publications and patents from mid-2004 through the first quarter of 2006. While the CRF type 2 receptor remains an intract Read More

Glucocorticoids have been used in modern clinical practice for over fifty years. Although they have demonstrated potent anti-inflammatory and immunosuppressive activities, their association with debilitating and lifethreatening side effects has been a major drawback. Recent insights into glucocorticoid biology have lent support to the hypothesis that the glucocorticoid anti-inflammatory activities could be dissociated from t Read More

Discovery of mAChR subtype selective M4 positive allosteric modulators. There are two types of cholinergic receptors through which the neurotransmitter acetylcholine (ACh) acts: nicotinic acetylcholine receptors (nAChRs), ligand gated ion channels, and muscarinic acetylcholine receptors (mAChRs), class A G protein-coupled receptors. To date, five mAChR subtypes have been identified (M1- M5) and are thought t Read More