Mini Reviews in Medicinal Chemistry - Volume 8, Issue 4, 2008

The management of HBV or HCV has improved dramatically over the last decade with the development of new drugs. This paper provides a review of new available and developing treatment options for HBV and HCV associated liver diseases. In the closer future the most realistic therapeutical option for most of the patients with HBV and HCV infection will be combination and/or long-term usage of the new, stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.

This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to “carbonyl stress” during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.

Non-steroidal anti-inflammatory drugs and aureolic acid group of anti-cancer drugs belong to the class of generic drugs. Research with some members of these two groups of drugs in different laboratories has unveiled functions other than those for which they were primarily developed as drugs. Here we have reviewed the molecular mechanism behind the multiple functions of these drugs that might lead to employ them for treatment of diseases in addition to those they are presently employed.

The platelet is an anucleate cell, complicating efforts to study platelet function by traditional genetic means. Discovery-based strategies have lead to the identification of pharmacological agents capable of targeting specific proteins critical for platelet activation. This review will address the evolution of discovery-based strategies to identify probes that are at once useful reagents for studying platelet activation and effective therapeutics.

The manipulation of glycosylation, mainly sialylation, holds enormous potential for understanding the biological functions of glycoproteins and glycolipids to treat many diseases. The existing knowledge in the field of glycobiology is exploited by glycotherapeutics for combating protozoan diseases. This review focuses on the development of novel glycobiological therapeutic strategies in the field of protozoan infections.

The discovery of the endocannabinoid system has lead to great strides in research development. At present, two cannabinoid receptors, CB1R and CB2R, are known. They belong to Class A rhodopsin-like GPCRs, and possess a different tissue distribution. Many synthetic compounds have been synthesized and tested for their cannabinoid activity. A particular class among them, the aminoalkylindole derivatives (typified by WIN55212-2) are hypothesized to interact in a binding site different from the main cannabinoid agonists. In this review we report the main aminoalkylindole derivatives, and other compounds which are hypothesized to interact in the same binding site. Furthermore we analyze the pharmacological profiles, the mutagenesis data and the computational models that describe their interaction in the cannabinoid receptors, evaluating the most important aspects for their activity and selectivity.

The propagation of cancer, which is basically the consequence of uncontrolled multiplication of cells, is a complicated process involving the participation of a number of enzymes. The molecular level understanding of the chemistry of these enzymes is the starting step towards the development of anti-cancer drugs and a collective view of these enzymes (responsible for cell multiplication) could help in the development of multiple target ligands. In this review, the mechanistic chemistry of the key enzymes viz. ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase, topoisomerase II, closely involved at various stages of cell multiplication and hence responsible for the propagation of cancer, and some of their suitable inhibitors have been discussed. Further, this review will elucidate the chemistry of lactate dehydrogenase and cyclooxygenase, the enzymes responsible for providing the extra energy to the cancer cells and initiating the growth of tumors through the formation of mutagens, respectively.

Iridoids represent a large group of cyclopenta[c]pyran monoterpenoids that occur wide-spread in nature, mainly in dicotyledonous plant families like Apocynaceae, Scrophulariaceae, Diervillaceae, Lamiaceae, Loganiaceae and Rubiaceae. Recently, more extensive studies revealed that iridoids exhibit a wide range of bioactivity, such as neuroprotective, antinflammatory and immunomodulator, hepatoprotective and cardioprotective effects. Anticancer, antioxidant, antimicrobic, hypoglycaemic, hypolipidemic, choleretic, antispasmodic and purgative properties were also reported. The aim of the present review is to discuss the recent developments on biological and pharmacological activities of iridoids, supporting the new therapeutic possibilities for the use of these compounds.