Mini Reviews in Medicinal Chemistry - Volume 10, Issue 11, 2010

Sol-gel technology is an impressive and instructive innovation in science that necessitates a multidisciplinary approach for its important applications in the practice. An important peculiarity of the sol gel technology is the possibility to control the mechanism and kinetics of the chemical reactions, thus monitoring the final structure (particle size, porosity, thin layer thickness) of the materials. The low processing temperature combined with the intrinsic bio-compatibility and environmental friendliness of the implied components makes it an ideal method applied in different biomedical purposes: the synthesis of porous matrices for entrapping of organic and inorganic compounds, sensor molecules, enzymes and many other biological molecules, selective coatings for optical and electrochemical biosensors, stationary phases for chromatography, immunoadsorbent and solid-phase extraction materials, controlled release agents, solid-phase biosynthesis, and unique matrices for biophysical studies. It is therefore the scope of this review to provide a few insights of the recent progresses made in sol-gel-based materials for biomedical applications.

There has been a considerable interest in the development of novel compounds with anti-inflammatory and /or antimicrobial activities. Several economical and social merits have been prospected for compounds with dual effects. Pyrazoles are an important class of compounds for new drug development that attracted much attention. Several pyrazole derivatives have been synthesized as target structures and evaluated for their biological activities. This review describes the synthesis and the development of new pyrazoles that possess anti-inflammatory and /or antimicrobial activities. The cytotoxicity of the reported compounds indicates good safety associated with many of the pyrazole derivatives. However, the need for standardized method for cytotoxicity evaluation is required for better understanding of the compounds safety and the safety-structure relationships.

Epigenetic alterations occur throughout the development and carcinogenesis of gastric cancer. Therefore, the detection of methylated DNA markers is predicted to be able to detect gastric cancer earlier, and improve the risk assessment, surveillance, relapse, and prognosis of patients with gastric cancer. Detection of free methylated DNA also represents a promising approach for developing serum-based detection methods for the non-invasive monitoring of gastric cancer progression.

The atmospheric pollutant sulfur dioxide (SO2) is endogenously generated from the normal metabolism of sulfur- containing amino acids through the aspartate aminotransferase pathway. SO2 is produced in cardiovascular tissues, and the aspartate aminotransferase mRNA is localized in endothelia and in vascular smooth muscle cells near the endothelial layer. Recent studies explored the physiological and pathophysiological effects of endogenous SO2 on the cardiovascular system, and various potential mechanisms were found. These discoveries suggest a novel role of endogenous SO2 in the modulation of the cardiovascular system and provide a basis for new treatments for cardiovascular diseases.

HIV-1 integrase (IN), which has no cellular counterpart, has been intensely studied over the past 15 years and has been fully validated as a therapeutic target with the first FDA approved IN inhibitor raltegravir. The quinolone acid GS-9137 (elvitegravir), which most probably will become the next candidate of IN inhibitors, is in the process of enrolling patients in the phase III clinical trials. This review focuses on small-molecular of quinolone acid derivatives, which have the similar pharmacophore of β-diketoacids, as integrase inhibitors with antiviral activity.

The cell cycle is the series of events necessary for the division and duplication of a cell. The dysregulation of the cell cycle can promote the development of cancer. A group of proteins, cyclin-dependent kinases (CDKs), that control the cell cycle, provide new targets for treating cancer. As a result, cyclin-dependent kinase inhibitors (CDKIs) represent a novel class of chemotherapeutic agents. Of these, flavopiridol, a semisynthetic flavonoidal alkaloid, emerged as the first CDKI to enter clinical trials. Preclinical data indicate that flavopiridol could block the proliferation of neoplastic cells and induce programmed cell death as a single agent. Furthermore, recent emerging data revealed that flavopiridol can potentiate, generally in a dose- and sequence-dependent manner, the anti-tumor effects of many established chemotherapeutic agents. This review is primarily focused on the role of flavopiridol in combination with various therapeutic agents that are in or near clinical development.

This review proposes a statistical and qualitative comparison between the main techniques derived from the original PAMPA method and experimental results obtained from Caco-2 and human jejunum. Among them, PAMPA techniques variations developed by some of the most renowned authors on the subject. The comparison is made from 16 common structurally diverse molecules, taking into account mainly membrane lipid composition and incubation conditions. A BCS classification prediction of the studied molecules was also possible to make. Finally, it was possible to raise and prove important previous hypotheses, aside from pointing out the best PAMPA model to predict human data.

This review covers natural products isolated from marine microorganisms including bacteria, fungi and actinomycetes published in the recent years. The emphasis is mainly about new compounds, together with their antibacterial activities, source organisms and country of origin, biosynthetic studies as well as the mechanisms involved in their anti-bacterial activities.