Bioinspired Pyrano[2,3-]chromen-8-ones: Ring C-Opened Analogues of Calanolide A: Synthesis and Anti-HIV-1 Evaluation.

We have designed and synthesized a series of bioinspired pyrano[2,3-]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2,8-pyrano[2,3-]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction.

Dual-targeted anti-CMV/anti-HIV-1 heterodimers.

Despite the development of efficient anti-human immunodeficiency virus-1 (HIV-1) therapy, HIV-1 associated pathogens remain a major clinical problem. Human cytomegalovirus (CMV) is among the most common HIV-1 copathogens and one of the main causes of persistent immune activation associated with dysregulation of the immune system, cerebrovascular and cardiovascular pathologies, and premature aging. Here, we report on the development of dual-targeted drugs with activity against both HIV-1 and CMV.

DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs.

This short review is focused on enzymatic properties of human ATP-dependent RNA helicase DDX3 and the development of antiviral and anticancer drugs targeting cellular helicases. DDX3 belongs to the DEAD-box proteins, a large family of RNA helicases that participate in all aspects of cellular processes, such as cell cycle progression, apoptosis, innate immune response, viral replication, and tumorigenesis. DDX3 has a variety of functions in the life cycle of different viruses.

Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation.

Hepatitis C virus (HCV) triggers massive production of reactive oxygen species (ROS) and affects expression of genes encoding ROS-scavenging enzymes. Multiple lines of evidence show that levels of ROS production contribute to the development of various virus-associated pathologies. However, investigation of HCV redox biology so far remained in the paradigm of oxidative stress, whereas no attention was given to the identification of redox switches among viral proteins.

Synthesis and Biological Evaluation of Novel Thymidine Analogs Containing 1-1,2,3-Triazolyl, 1-Tetrazolyl, and 2-Tetrazolyl Fragments.

3'-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1- and 2-propargyl-5-R-2-tetrazoles (R = H, Me, CHCOOEt, CHCON(CH), Ph, 2-CH-CH, or 4-NO-CH) the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3'-modified thymidine analogs incorporating 1-1,2,3-triazolyl, 1-, and 2-tetrazolyl fragments in 41-76% yield. The structures of the obtained compounds have been elucidated by means of HRESI-MS, H and C{H} NMR, and single crystal X-ray diffraction {for 3'-[4-(1-5-,-dimethylaminocarbonylmethyltetrazol-1-yl)-1-1,2,3-triazol-1-yl]thymidine }. biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1.