Mini Reviews in Medicinal Chemistry - Volume 10, Issue 4, 2010

The rapid emergence of drug resistance intensified the search for new antimicrobial agents, leading to lots of novel derivatives obtained from 14- and 15-membered macrolides by chemical modifications. Many of them exhibited enhanced antibacterial activity and expanded antibacterial spectrum. Especially some of them were found to be potent for the treatment of multi-drug-resistant bacterial infections. Besides, the other biological effects of macrolide derivatives were also found. In this article, we reviewed the recent advance in the novel macrolide derivatives designed by different structural modifications on erythronolide skeleton, cladinose and desosamine in the structures.

Since most of the proteinogenic α-amino acids contain a chiral carbon atom, the stereoisomers of both these amino acids and the peptides in which they are to be found may possess differences in biological activity in living systems. The important analytical task of the separation of optical isomers is achieved mainly by chromatographic methods. This special review surveys direct and indirect HPLC separations of biologically important, small epimeric peptides and their L,D-amino acid content.

The aim of this review is to summarize the most comprehensive results in the field of bis-aromatic compounds targeting DNA and RNA, whereby both aromatic units of small molecule bind to the polynucleotide by the aromatic stacking interactions. The most recent results about structure - DNA/RNA binding affinity, selectivity and biological implications are discussed for bis-intercalators, sterically restricted macrocyclic and threading bis-aromatics and intercalator - nucleobase conjugates.

Although the halogen bond has attracted much interest in chemistry and material science communities, its implications for drug design are just now coming to light. The protein-ligand interactions through short halogen— oxygen/nitrogen/sulfur contacts have been observed in crystal structures for a long time, but only in recent years, with the experimental and theoretical progress in weak biological interactions, especially the pioneering works contributed by Ho and co-workers (Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Proc. Natl. Acad. Sci. USA 2004, 101, 16789-16794), these short contacts involving halogens in biomolecules were rediscovered and re-recognized as halogen bonds to stress their shared similarities with hydrogen bonds in strength and directionality. Crystal structure determinations of protein complexes with halogenated ligands preliminarily unveiled the functionality of halogen bonds in protein-ligand recognition. Database surveys further revealed a considerable number of short halogen-oxygen contacts between proteins and halogenated ligands. Theoretical calculations on model and real systems eventually gave a quantitative pronouncement for the substantial contribution of halogen bonds to ligand binding. All of these works forebode that the halogen bond can be exploited as a new and versatile tool for rational drug design and bio-crystal engineering.

The inhibition of α-glucosidase and α-amylase, enzymes involved in the digestion of carbohydrates, can significantly reduce the post-prandial increase of blood glucose and therefore can be an important strategy in the management of blood glucose level in type 2 diabetic and borderline patients. Currently, there is renewed interest in plant-based medicines and functional foods modulating physiological effects in the prevention and cure of diabetes and obesity. The plant kingdom is a wide field to search for natural effective oral hypoglycaemic agents that have slight or no side effects. More than ca. 1200 plant species have been recorded to be used empirically worldwide for their alleged hypoglycaemic activity. Therefore, natural α-glucosidase and α-amylase inhibitors from plant sources offer an attractive strategy for the control of hyperglycaemia. This article reviews recent data on plant extracts and isolated natural compounds that are being tested for their hypoglycaemic activity, highlights ongoing research and considers the future perspectives.

Photodynamic therapy (PDT) is a versatile methodology to treat various diseases but the drugs (photosensitizers) specifically aimed at individual character of diseases are urgently needed. Among those, the perilenoquinoid photosensitizers were thought of low PDT effectiveness to solid tumors due to low absorption on the “photodynamic window” but may be specially suitable for PDT to some microvascular diseases, such as age-related macular degeneration (AMD) and port wine stains (PWS), as well as other superficial diseases. Two strategies were discussed to convert the photosensitizers into clinically acceptable drugs in consideration of the drug-delivery and biological activity.

The antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase contribute dominatingly to enhance cellular antioxidant defense against oxidative stress. They act cooperatively to scavenge reactive oxygen species, and not one of them can singlehandedly clear all forms of reactive oxygen species. On the basis of the structural understanding for these natural enzymes, many mimics with multifunctional activities had been obtained by chemical synthesis, biosynthesis, and protein fusion techniques. Some of them display remarkable antioxidant cooperative effect in living model which possess potential application in medicine as potent antioxidants. This review summarizes aspects of some multifunctional mimics which have been reported so far.