Mini Reviews in Medicinal Chemistry - Volume 10, Issue 2, 2010

Rheumatoid arthritis (RA) is mainly an auto-immune disease characterized by inflammation in joints. 1 in 50 people develop RA at some stage and at any age. This review summarizes the etiology, pathophysiology, risk factor, and treatment related to RA. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on RA.

The polyplexes which are formed between cationic polymers and DNA through electrostatic interactions and thus known as polycation/DNA complexes, are by far the most widely used non-viral gene delivery vectors. Many factors such as molecular weight, surface charge, charge density, hydrophilicity and the structure of cationic polymers affect gene transfection efficiency of cationic polymers. Therefore, optimization of cationic polymers is necessary to improve the gene transfection efficiency. Currently several important cationic polymers were used as cationic vectors for gene delivery which included PEI, PLL, Chitosan and PAMAM. Their most advantages and the rational design are introduced in this article. However, these systems are much less efficient in gene transfer experiments compared with viral systems. Some strategies such as PEGylation, combination and multifunctional modification were developed in the cationic polymeric vectors for gene delivery. Hereby, this article will review various kinds of copolymers with higher stability but biodegradable, bioresponsive and easy refined molecular weight which could be easily modification. Especially, the multifunctional modified polyplexes and polymersomes will be further discussion due to their ability to conjugate biologically active ligands, which can be used as potential nanostructured biomaterials for future in vivo gene delivery.

Currently, polycationic nanoparticles (polycation) as nonviral vectors are promising to overcome the defects of traditional viral vectors. This review focuses on the recent progress and challenges to improve the transfection efficacy and circulation time of polyplexes (complexes between polycation and pDNA or oligonucleotides such as siRNA ) in vivo.

Aberrant Ret kinase activity has been implicated in multiple carcinomas and disorders. Many strategies have been implemented to identify Ret kinase inhibitors. This review details current efforts to discover novel small molecule Ret kinase inhibitiors. Furthermore, we compile a comprehensive list of Ret kinase inhibitors and describe clinical results of advanced assets with Ret inhibitory activity.

AIDS, the fatal disease, caused in human by the fast spreading human immunodeficiency virus (HIV), was detected in 1981. To check its rapid growth, affecting various parts of the world population, there are various FDA approved drugs, released in the market for treating AIDS. These belong to 5 different categories which differ in their mechanism of action. These are i) reverse transcriptase inhibitors, ii) protease inhibitors, iii) fusion inhibitors, iv) entry inhibitors and v) HIV integrase strand transfer inhibitors. These drugs are mostly used in a combination therapy, named as Highly Active Anti Retroviral Therapy (HAART), using 2 to 3 compounds in combination, for a more effective and beneficial treatment. However, none of the drugs can be considered ideal for curing the disease. A study of structural requirement for different types of anti-HIV activities may help in designing a suitable drug for AIDS.

Hepatitis B virus (HBV) infection is a severe health problem all over the world. However, there is still no satisfactory anti-HBV therapeutic strategy. Currently, promising alternative approaches toward the control of HBV infection include the development of structurally novel and more potent inhibitors obtained from natural products and structural modifications of synthetic molecules as seen in many cases. In this review, we will focus our interest on representative naturally occurring and synthetic small molecule non-nucleoside inhibitors with high anti-HBV potency and potential for future therapeutic regimens to combat HBV infection.

Photo-sensitive liposomes have been studied for a few decades and various photo-sensitive triggers have been developed so far. This review offers an overview of the different photo-triggering mechanisms for controlled pulsatile content release from liposomes, which have the potential of finding clinical applications as intelligent drug delivery systems.