Current Medicinal Chemistry - Volume 22, Issue 34, 2015

In the current context of antiviral drug development, which has been traditionally dominated by herpesviruses, human immunodeficiency virus (HIV) and hepatitis C virus (HCV), a new viral target has been recently gained unforeseen attention, Ebola virus. Ten nucleoside analogues, or categories thereof, are reviewed for their therapeutic potential as antiviral drugs: (i) BCX4430, a C-nucleoside; (ii) 4’-azido-, 4’-cyano-, a Read More

Thiarabine has demonstrated exceptional antitumor activity against numerous human tumor xenografts in mice, being superior to gemcitabine, clofarabine, or cytarabine. Unlike cytarabine, thiarabine demonstrated excellent activity against solid tumor xenografts, suggesting that this agent has the kind of robust activity in animal models that leads to clinical utility. Thiarabine is effective orally (bioavailability of approximately Read More

Transition-state analysis based on kinetic isotope effects and computational chemistry provides electrostatic potential maps to serve as blueprints for the design and chemical synthesis of transition-state analogues. The utility of these molecules is exemplified by potential clinical applications toward leukemia, autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial antibiotics. In some cases, transitio Read More

As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nu Read More

Regardless of significant improvement in the area of anti-HBV therapy, resistance and cross-resistance against available therapeutic agents are the major consideration in drug discovery of new agents. The present study is to obtain the insight of the molecular basis of drug resistance conferred by the B and C domain mutations of HBV-polymerase on the binding affinity of four anti-HBV agents [Adefovir (ADV), Tenofovir (TNF), Ent Read More

The bio-reversible protection of nucleoside diphosphates is summarized. The design, hydrolytic characteristics, and the antiviral activity of these prodrugs of NDPs are described. In contrast to earlier attempts, the DiPPro-approach [β-(bis(acyloxybenzyl) nucleoside diphosphates)] leads to the successful delivery of the desired nucleoside diphosphates. The stability towards hydrolysis is dependent on the specific acyl moieties in Read More

The continued emergence of drug-resistance to existing antibacterial agents represents a severe and ongoing public health concern, which demands the discovery of new antibiotics. However the number of novel classes of antibacterial drugs launched in the clinic has been remarkably slow since the 1960s, and it is urgent to develop novel antibacterial agents to fight against drug-resistant bacterial pathogens. Peptidogl Read More

Over the past few decades, different types of nucleoside phosphate-conjugates have been under extensive investigation due to their favorable molecular lability with interesting catalytic hydrolysis mechanisms, recognition as polymerase substrates, and especially for their development as antiviral/ anticancer protide therapeutics. The antiviral conjugates such as nucleoside phosphoesters and phosphoramidates that were d Read More

About 500 NAD (P)-dependent enzymes in the cell use NAD (P) as a cofactor or a substrate. This family of broadly diversified enzymes is crucial for maintaining homeostasis of all living organisms. The NAD binding domain of these enzymes is conserved and it was believed that NAD mimics would not be of therapeutic value due to lack of selectivity. Consequently, only mycophenolic acid which selectively binds at the cofactor Read More