A5060158781- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Cytomegalovirus and herpesvirus research
- Synthesis and Characterization of Heterocyclic Compounds
- HIV Research and Treatment
- Tuberculosis Research and Epidemiology
- Click Chemistry and Applications
- DNA and Nucleic Acid Chemistry
- Organophosphorus compounds synthesis
- Herpesvirus Infections and Treatments
- Adenosine and Purinergic Signaling
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Quinazolinone synthesis and applications
- Cancer therapeutics and mechanisms
- Hepatitis C virus research
- Toxoplasma gondii Research Studies
- Synthesis and Biological Evaluation
- SARS-CoV-2 and COVID-19 Research
- Polyomavirus and related diseases
- Mycobacterium research and diagnosis
- DNA Repair Mechanisms
- Ferrocene Chemistry and Applications
- RNA modifications and cancer
- Synthesis and biological activity
Engelhardt Institute of Molecular Biology
2015-2024
University of Baltimore
2013-2015
Russian Academy of Sciences
2008-2010
Weatherford College
2010
Institute of Bioorganic Chemistry
2004
Institute of Experimental Cardiology
2002
State Research Center of Virology and Biotechnology VECTOR
2001
S-Adenosyl-l-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs SAM with a reporter group in place the S-methyl are widely used to study these However, many analogs chemically unstable that largely limits practical application. We have developed new compound, SAM-PH , which contains an H-phosphinic (-P(O)(H)OH) instead carboxylic group. SAM-P H is significantly more stable than SAM, retains functional...
Key biological targets (S-adenosyl-L-homocysteine hydrolase, telomerase, human immunodeficiency virus reverse transcriptase, herpes DNA polymerase and hepatitis B polymerase) the mechanisms of action carbocyclic nucleoside analogues are considered. Structural types discussed. Methods synthesis for most promising compounds spectrum their activities described. The bibliography includes 126 references.
A series of novel 5′-norcarbocyclic derivatives 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity compounds evaluated against both Gram-positive Gram-negative bacteria. The growth Mycobacterium smegmatis was completely inhibited by most active at a MIC99 67 μg/mL (mc2155) 6.7–67 (VKPM Ac 1339). Several also showed ability to inhibit attenuated strains tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) bovis 35737 50–60 μg/mL), as well two virulent M. tuberculosis;...
Abstract Analogues and derivatives of nucleic acid components have been used as key drugs in different areas medicine over the past decades. The replacement one or more nitrogen atoms heterocyclic base with a CH group affords deazapurine nucleoside analogues, methine atom gives azapurine derivatives. A combination aza deaza moieties purine leads to aza(deaza)-modified bases. Some analogues were found exhibit pronounced anticancer antiviral activity. synthesis evaluation biological activity...
Pyrimidine nucleoside analogues are widely used to treat infections caused by the human immunodeficiency virus (HIV) and DNA viruses from herpes family. It has been shown that 5-substituted uracil derivatives can inhibit HIV-1, family viruses, mycobacteria other pathogens through various mechanisms. Among pyrimidine nucleosides, there not only classical inhibitors of 2′-deoxy-5-iodocytidine 5-bromovinyl-2′-deoxyuridine, but also 1-(benzyl)-5-(phenylamino)uracil, which proved be...
Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, and 1,3-di-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, were synthesized screened for potential antimicrobial activity. Most compounds had a negative effect on the growth Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 40 μg/mL. Of those,...
Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives AZT d4T were synthesized evaluated as anti-HIV agents. The efficacy some the compounds in cell cultures infected with HIV-1 was higher than that parent nucleosides only slightly correlated to their stability phosphate buffer human blood serum. phosphonates are most probably prodrug forms corresponding nucleosides.
Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories two structurally related scaffolds shown promising activity against both Mycobacterium tuberculosis several parasitic strains. As result, small structure relationship study was designed to further probe their potential. Their synthesis the of subsequent biological are reported herein.
The SARS-CoV-2 betacoronavirus pandemic has claimed more than 6.5 million lives and, despite the development and use of COVID-19 vaccines, remains a major global public health problem. specific drugs for treatment this disease very urgent task. In context repurposing strategy, we previously screened library nucleoside analogs showing different types biological activity against virus. screening revealed compounds capable inhibiting reproduction with EC50 values in range 20-50 µM. Here present...
We have recently shown that neither the base nor sugar moieties of a nucleotide is an essential feature for its incorporation by DNA polymerases (pols) lambda and beta. Here we present identification novel non-nucleoside triphosphate (NNTP) derivatives belonging to three classes: (i) non-substrate-specific inhibitors pol lambda; (ii) substrate which could preferentially be incorporated either wild type or Y505A mutant (iii) inhibitor N-(Biphenylcarbonyl)-4-oxobutyl exclusively beta in...
The main disadvantages of 3′-azido-3′-deoxythymidine (zidovudine, AZT), the most common anti-HIV drug, are toxicity and a short half-life in organism. introduction an <i>H</i>-phosphonate group into AZT 5′ position resulted significant improvement its therapeutic properties allowed new Nikavir (AZT H-phosphonate). In this work, we described derivatives, namely, 5′-aminocarbonylphosphonates. synthesized compounds displayed antiviral cell cultures infected with HIV-1 capacity to release active...
An eco-friendly and scalable biotechnological method for fleximer nucleoside synthesis using E. coli cells overexpressing phosphorylases.
The life cycle of severe acute respiratory syndrome coronavirus 2 includes several steps that are supposedly mediated by liquid-liquid phase separation (LLPS) the viral nucleocapsid protein (N) and genomic RNA. To facilitate rational design LLPS-targeting therapeutics, we modeled N-RNA biomolecular condensates in vitro analyzed their sensitivity to small-molecule antivirals. model were obtained visualized under physiological conditions using an optimized RNA sequence enriched with N-binding...