A5069268349- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Tuberculosis Research and Epidemiology
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- Cancer therapeutics and mechanisms
- Mycobacterium research and diagnosis
- Synthesis and Biological Evaluation
- Quinazolinone synthesis and applications
- Synthesis and Characterization of Heterocyclic Compounds
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- Synthesis and biological activity
- DNA and Nucleic Acid Chemistry
- Catalytic Cross-Coupling Reactions
- Viral gastroenteritis research and epidemiology
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- Organophosphorus compounds synthesis
- Carbohydrate Chemistry and Synthesis
- Herpesvirus Infections and Treatments
- Phenothiazines and Benzothiazines Synthesis and Activities
- Ubiquitin and proteasome pathways
- Research on Leishmaniasis Studies
Engelhardt Institute of Molecular Biology
2015-2024
Weatherford College
2010
Russian Academy of Sciences
2009-2010
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,...
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...
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...
A new series of potential nonnucleoside inhibitors HIV-1 reverse transcriptase (NNRTIs) based on the carbocyclic 5′-nor-uracil scaffold were designed and synthesized. Three different aspects investigated: effects adding a linker between phenyl fragments, introduction substituents benzoyl residue replacing central ring with benzyl group. Analogues 2′,3′-dideoxy-2′,3′-didehydro-5′-nor-uridine, bearing 3,5-dichloro- or 3,5-dimethylbenzoyl groups, showed inhibitory activity against HIV-RT...
A new series of potential nonnucleoside inhibitors HIV-1 reverse transcriptase (NNRTIs) based on the carbocyclic 5′-nor-uracil scaffold were designed and synthesized. Binding modes in active site enzyme studied computationally to provide insight interactions. Several 2′,3′-dideoxy-2′,3′-didehydro-5′-nor-uridine analogues showed inhibitory activity against wild-type mutant (L100I) HIV-RT with Ki 13–18 μM 1–11 μM, respectively.
The mechanisms of action pyrimidine nucleoside derivatives on model lipid membranes various compositions were studied. A systematic analysis the tested agents’ effects membrane physicochemical properties was performed. Differential scanning microcalorimetry data indicated that ability to disorder lipids depended types bases and membrane-forming lipids. 5′-norcarbocyclic uracil found be ineffective, while N4-alkylcytidines demonstrated most pronounced effects, significantly decreasing...
The great interest in studying the structure of human purine nucleoside phosphorylase (hPNP) and continued search for effective inhibitors is due to importance enzyme as a target therapy T-cell proliferative diseases. In addition, hPNP are used organ transplant surgeries provide immunodeficiency during after procedure. Previously, we showed that members well-known fleximer class nucleosides substrates E. coli PNP. Fleximers have promise they exhibited significant biological activity against...
Widespread latent herpes viral infections within a population can lead to the development of co-infections in HIV-infected patients. These are not particularly dangerous for healthy individuals and often occur with minimal symptoms, but those who immunocompromised, these accelerate acute phase HIV infection AIDS. Thus, idea designing compounds that could combine activity against would seem promising. In regard, eleven were synthesized represent conjugates non-nucleoside reverse transcriptase...
Abstract 5′-Norcarbocyclic analogues of furano[2,3- d ]pyrimidine nucleosides as well 5-bromo and 5-iodouracil derivatives were synthesized to evaluate their potential antitumor activity. The halogenated display no cytotoxicity with respect all tested cells: KB-3-1 (human epidermoid carcinoma), HeLa cervical epithelioid HuTu-80 duodenal cancer), B16 (mouse melanoma), MDCK (normal epithelial). the non-halogenated increases lengthening alkyl chain substituent from 45 60 μ m for octyl 3 10 dodecyl.