Mini Reviews in Medicinal Chemistry - Volume 6, Issue 5, 2006

ACE Inhibitors (ACEI) and angiotensin receptor blockers (ARB) inhibit the renin-angiotensin system, but ACEI may do so incompletely when administered as monotherapy at conventional doses. In theory, combining an ACEI and ARB might be beneficial, whereas clinical evidence for this approach in hypertension is lacking. An ACEI-ARB combination is likely to be useful in proteinuric renal disease, but recent experimental Read More

Imiquimod is a synthetic imidazoquinoline heterocyclic amine of 240.3 Da (C14H16N4). Imiquimod is a cytokine inducer and a modifier of the innate immune response, as well as acquired antiviral and antitumor immune responses. Imiquimod 5% cream has proven to be an effective treatment for external genital warts, superficial basal cell carcinoma, and actinic keratosis.

Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (statins) are widely used for the prevention of atherosclerotic diseases. The effects of statins on the generation of reactive oxygen species (ROS) by in vitro and in vivo were studied. Administration of statins significantly decreased ROS generation in vitro and in vivo.

CD4+CD25+ T cells are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models revealed that Treg are potent inhibitors of an anti-tumor immune response. Treg are expanded in human cancer. Currently, a variety of strategies for the induction of a specific anti-tumor immune response are tested in preclinical and clinical settings. Biochemical strate Read More

While most inhibitors of histone deacetylases (HDACs) are hydroxamic acid derivatives, several nonhydroxamates have recently been developed as inhibitors and attracted quite a deal of attention. In this review, we present the rational design, inhibitory effect and antiproliferative activity of non-hydroxamate HDAC inhibitors.

Hepatitis C virus represents a major global health problem, with approximately 3% of the world population infected. Immune-response modifiers represent the standard of care, given the lack of approved antiviral agents having direct activity against the viral proteins. Although in recent years, improvements in therapy have been attained by combined treatment with pegylated interferon and ribavirin, the discovery and develop Read More

This review focuses on the synthesis and mechanisms of antitumor activity of cationic nonphosphorus analogs of edelfosine. The role of variable length and mode of conjugation of the spacer group, the types of cationic 'head', and the length of the substituent at C(2) atom of the glycerol backbone are discussed, providing the basis for rational design of lipophilic anticancer drugs, in particular, for elimination of multidrug r Read More

Japanese traditional herbal medicine, which is known as "Kampo", has received increasing attention as an alternative approach to the treatment of various diseases. In order to safely and effectively apply Kampo, it is essential to understand oriental diagnostics. Herein, an outline of such diagnostics is introduced, and current trends in Kampo research are reviewed.

The causative agent of acquired immunodeficiency syndrome, HIV-1, depends on one of its enzymes, reverse transcriptase, to copy its single stranded RNA genome into a double stranded DNA nucleic acid suitable for integration in the host cell genome. In the last two decades, the advances in the knowledge of the kinetic mechanism of reverse transcription and in the determination of the crystallographic structures Read More

Drugs that block the entry of human immunodeficiency virus type 1 (HIV-1) into host cells abrogate the establishment of a productive infection and should ideally diminish the chances of HIV-1 developing resistance. This review will give an overview of the mechanism by which the envelope glycoprotein mediates HIV-1 entry and will summarize current drug developments.

Type 2 diabetes mellitus (T2DM) is highly prevalent chronic disease. Recently, many biological targets are discovered for treatment of this disease. The identification of the nuclear hormone receptor peroxisome proliferator activated receptors (PPAR) and their subtypes α, γ and δ or β as targets for controlling lipid, glucose and energy homeostasis has proved to be exciting. As hyperlipidaemia, obesity and insulin resistance are in Read More

More recently, three novel purine nucleoside analogs, including clofarabine, nelarabine and immucillin H, have been introduced into clinical trials. These agents have different metabolic properties, novel mechanism of action, and are undergoing phase I-II clinical studies for the treatment of hematopoietic malignancies. Pharmacology and anticancer activity of PNA are the subjects of this review.

The plasma membrane calcium/calmodulin dependent ATPase (PMCA) is a calcium-extruding enzymatic pump important in the control of intracellular calcium concentration. PMCA is the only system for calcium extrusion in the majority of cells. In excitable cells such as cardiomyocytes however, PMCA has been shown to play only a minor role in calcium homeostasis. In these cells the main mechanism of calcium extrusi Read More

Considerable information on the functions of prion protein (PrP) has been accumulated. One experimental approach is the use of PrP gene-knockout mice and derived cell lines. This approach has contributed to elucidating the functions of cellular prion protein (PrPC), such as its anti-oxidative and anti-apoptotic roles. This review will introduce the recent advances in prion biology made possible by the availability of these tools.

In this review, we show Angiotensin-(1-7) as a novel Renin Angiotensin System mediator that antagonizes cardiovascular and proliferative effects of Angiotensin II and exerts complex renal actions. We also speculate the possibility of new drugs for the treatment of cardiovascular, genitourinary and hepatic diseases by interfering with ACE2- Angiotensin-(1-7)-Mas axis.