Mini Reviews in Medicinal Chemistry - Volume 7, Issue 3, 2007

Several classes of compounds (thioureas, ureas, β-glucosides, sulfonamides, and cyclic peptides) show enhanced binding affinity and selectivity at somatostatin subtype 4 receptors (sst4). Pharmacophore models have recently been proposed to explain receptor subtype selectivity. The chemistry and therapeutic potential of sst4 ligands will be the subject of this review.

Novel compounds have been developed that (in many cases) inhibit cholinesterases and concomitantly interact with at least one further pharmacological target, such as 5-HT3 or H3 receptors. But also enzymes like monoamine oxidase and the serotonin transporter have been targeted. Hybrid molecules can also incorporate antioxidant or neuronal Ca2+- channel-blocking structures.

Increasing number of new drugs, drug formulations and drug delivery systems is evaluated using noninvasive imaging methods. A successful use of new drugs and radiopharmaceuticals depends on their proven quality. This review provides a brief outline of the quality control procedures required for radiolabeled drugs within the context of the existing regulations.

Breast cancer remains a leading cause of death despite early screening and advances in medicine. Bone marrow metastasis often complicates the clinical picture by requiring more aggressive treatment and worsening long-term prognoses. Recent therapeutic targeting of hormonal receptors such as human epidermal growth factor receptor 2 and estrogen receptor has shown limited success in treating localized disease for those patients whose cancer cells are responsive. Although traditional approaches such as chemotherapy have demonstrated many successes, these agents fail to target quiescent cancer stem cells, which might have entered the bone marrow where they might be responsible for the quiescence population. Following years of clinical remission, these dormant cells could lead to secondary cancer resurgence. To date, little progress has been made in the development of targeted treatments for receptor negative and metastatic disease. In this review, we discuss the role of G-protein coupled receptors, including neurokinin-1, neurokinin-2 and chemokine receptor 4, as novel targets in the treatment of breast cancer.

CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV) activity that is expressed on numerous cell types and has a multitude of biological functions. An important aspect of CD26 biology is its peptidase activity and its functional and physical association with molecules with key roles in various cellular pathways and biological programs. CD26 role in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. Recent work also suggests that CD26 has a significant role in tumor biology, being both a marker of disease behavior clinically as well as playing an important role in tumor pathogenesis and development. In this paper, we will review emerging data that suggest CD26 may be an appropriate therapeutic target for the treatment of selected neoplasms and immune disorders. Through the use of various experimental approaches and agents to influence CD26/DPPIV expression and activity, such as anti-CD26 antibodies, CD26/DPPIV chemical inhibitors, siRNAs to inhibit CD26 expression, overexpressing CD26 transfectants and soluble CD26 molecules, our group has shown that CD26 interacts with structures with essential cellular functions. Its association with such key molecules as topoisomerase IIα , p38 MAPK, and integrin β1, has important clinical implications, including its potential ability to regulate tumor sensitivity to selected chemotherapies and to influence tumor migration/metastases and tumorigenesis. Importantly, our recent in vitro and in vivo data support the hypothesis that CD26 may indeed be an appropriate target for therapy for selected cancers and immune disorders.

Ethnomedicinal plants have been used as source of candidate drugs for almost all diseases, but the number of compounds having antiviral activity is scarce. Irrespective of type of viruses and the cells they infect, there are a very few specific viral targets for the natural molecules to interact. Most of the available antiviral drugs often lead to the development of viral resistance coupled with the problem of side effects, recurrence and viral latency. A wide array of ethnomedicinal plants showed high level of antiviral activities and many of them have complementary and overlapping mechanism of action, either inhibiting viral replication, or viral genome synthesis. Hence, there is an urgent need to develop new antivirals of natural origin. This review will cover some of the promising antiviral compounds isolated from ethnomedicinal plants with proven in vitro and some documented in vivo activities, along with their structure activity relationship.

Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive 10B nucleus and low-energy (thermal) neutrons for the destruction of tumour cells. If boronated agents are targeted towards chromosomal DNA, the efficiency of BNCT is greatly enhanced. This article presents a concise review of DNA-binding compounds that have been functionalised with boron.

α-tocopherol is a very well-known potent antioxidant and radical scavenger in chemical and biological systems. Its structure has served as starting point for design and synthesis of more potent antioxidant analogues with regard to its potential clinical and nutritional applications in human health. Furthermore, in recent years, intense research has been made not only in the development of hybrid compounds with classical drug moieties in a single molecule, but also in the preparation of label analogues with application in tocopherol metabolism studies. In the present review principal progresses in these aspects are outlined.

Raxofelast, also named IRFI 016 or (±)5-(Acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic acid, belongs to a family of novel molecules designed with the aim to maximize antioxidant potency of phenols related to Vitamin E ( α-tocopherol). This review will focus on the antioxidant and radical scavenging activity of this new promising compound.