Current Pharmaceutical Design - Volume 20, Issue 5, 2014

Drug resistance is a common concern for the development of novel antiviral, antimicrobial and anticancer therapies. To overcome this problem, several strategies have been developed, many of which involving the theme of this review, the use of structure-based drug design (SBDD) approaches. These include the successful design of new compounds that target resistant mutant proteins, as well as the development of Read More

The treatment for hepatitis C virus (HCV) infection has been significantly improved with the approval of the first two HCV NS3/4A protease inhibitors, telaprevir (Incivek) and boceprevir (Victrelis). These two direct acting antivirals (DAAs) are used clinically in combination with pegylated interferon-alpha (PEG-IFNα) and ribavirin (RBV). The sustained virologic response (SVR) rates are increased to ~70% and the duration of Read More

The emergence of drug resistance has devastating economic and social consequences, a testimonial of which is the rise and fall of inhibitors against the respiratory component cytochrome bc1 complex, a time tested and highly effective target for disease control. Unfortunately, the mechanism of resistance is a multivariate problem, including primarily mutations in the gene of the cytochrome b subunit but also activ Read More

Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant R Read More

Acetohydroxyacid synthase (AHAS) (EC 2.2.1.6) (also known as acetolactate synthase) is the first common enzyme in the branched chain amino acid (BCAA) biosynthesis pathway. This pathway is present in microorganisms and in plants but not in animals, making it an attractive target for both drug and herbicide discovery. The function of AHAS is to catalyze the conversion of two molecules of pyruvate to 2-acetolactate or Read More

Chitin biodegradation is linked to fungi cell differentiation, nematode egg hatching, arthropods morphogenesis and human defense against malaria and other pathogens infection as well. Two classes of enzymes for chitin degradation include glycosyl hydrolase (GH) family 18 chitinases and family 20 β-N-acetyl-D-hexosaminidases. However, more and more research papers have revealed that either GH 18 family chitinases or GH 2 Read More

Our incessant tug-of-war with multidrug resistant pathogenic bacteria has prompted researchers to explore novel methods of designing therapeutics in order to defend ourselves against infectious diseases. Combined advances in whole genome analysis, bioinformatics algorithms, and biochemical techniques have led to the discovery and subsequent characterization of an abundant array of functional small peptide Read More

Multidrug resistance (MDR) is a serious problem that hampers the success of cancer pharmacotherapy. A common mechanism is the overexpression of ATP-binding cassette (ABC) efflux transporters in cancer cells such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2) that limit the exposure to anticancer drugs. One Read More