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Radioprotective and Antiviral Means

#A-1228


Elaboration and Investigation of Prospective Means Having Radioprotective and Antiviral Activities against the Sequels of Bioterrorism

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • MED-DRG/Drug Discovery/Medicine
  • BIO-CHM/Biochemistry/Biotechnology
  • MED-RAD/Radiomedicine/Medicine

Status
3 Approved without Funding

Registration date
13.01.2005

Leading Institute
Yerevan State University, Armenia, Yerevan

Supporting institutes

  • Scientific Technological Center of Organic and Pharmaceutical Chemistry / Institute of Fine Organic Chemistry, Armenia, Yerevan

Collaborators

  • Katholieke Universiteit Leuven / Rega Institute for Medical Research, Belgium, Leuven\nUniversity of Georgia / Colledge of Pharmacy, USA, GA, Athens\nUniversität Rostock / Institut fuer Chemie, Germany, Rostock\nPrinceton Biomolecular, USA, NJ, Princeton

Project summary

The problem of terrorism, and in particular, of bioterrorism is quickly becoming a reality for many countries of the world, including Armenia. Any country is not guaranteed against the possible extraordinary situations arising in consequence of a nuclear terrorism or the use of a “biological weapon” by terrorists exposition of a big contingent of people to the influence of genetically mutated drug-resistant pathogens, as it happened in the USA in the autumn of 2001 when the spores of Bacillus anthraces were spread with postal consignment. Any country also is not guaranteed against spontaneously arising new highly pathogenetic strains of viruses as, for instance, those of chicken influenza and atypical pneumonia, which raged quite recently in China and Thailand. Consequently, the elaboration of new radioprotective/radiotherapeutic and antiviral drugs, including those in which the above-mentioned properties can efficiently be combined, is an essential task to ensure the safety of any country and an environment from negative influences of radiation and chemical intoxicant.

The aims of the project are:

1. Elaboration of biologically active new compounds displaying a high pharmacological activity, a lower toxicity and a high selective action, making use of the method of synthesis bioisosteric analogies, among:


a) the heterocyclic systems containing lactone, and quinoline rings in the molecule;
b) the synthetic derivatives of benzylethanolamine, the semi-synthetic derivatives of Cucurbitacine and Shikonine;
c) the substituted diazaadamantanes and diazabicyclononanes;
d) the amides and diamides of substituted acetic and N-(2-oxo-1-oxaspiro/4,5/decane)-4-carboxylic acids;
e) new optically active non-proteinic (S)- and (R)-a-aminoacids with various aliphatic, aromatic and heterocyclic substituents in a lateral rink, applying a method of asymmetric synthesis.
2. To study the antioxidant and radiomodifying activities of the synthesized compounds under in vitro and in vivo experimental conditions.
3. To study antiviral activity of synthesized compounds.
4. To perform the biological screening and to study the structure - activity relationship (SAR) of the synthesized compounds, something, which provides the possibility, not only to select new and most effective biologically active substances, but also to create scientific bases for the synthesis of compounds displaying antiviral and radioprotective properties.
5. To select active compounds for a more detailed screening and preclinical investigations.

The project includes also a reorientation of the scientific staff within the framework of defensive programs for performing the bioorganic Schemas aimed at the preparation of medicinal drugs.

For the synthesis of the above-mentioned compounds, we propose to use the method of synthesis of the bioisosteric analogies of obviously active substances for the preparation of new physiologically active compounds. A bioisoster is a compound, obtaining by substituting an atom (a group of atoms) by another atom (group of atoms), retaining biological activity of the initial compound. This provides the possibility, in non-traditional systems, of creating more efficient and safe medical drugs. Such a substitution leads to the synthesis of new compounds having a high pharmacological activity, a lower toxicity, a high selectivity of action and others improved pharmacokinetic features. In order to be bioisosteric, two physiologically active substances must have similar hydrophobic, electronic and steric characteristics.

The following tasks will be solved as a result of the fulfillment of the project:


· Creation of potential medicinal drugs displaying an antiviral and/or radioprotective activity on the basis of natural, semi-synthetic and synthetic derivatives of O-, N- and S-containing organic compounds;
· Reorientation of a highly qualified scientists staff for the solution of peaceful problems;
· A subsequent integration of the scientists working in the sphere of armaments, in the international association of scientists.

For the accomplishment of the above mentioned aims of the project, efforts of highly qualified researchers of five leading laboratories of fine organic synthesis and of two laboratories specialized in the testing of antiviral and radioprotective activities of the synthesized compounds will be enclosed. The following take part in the fulfillment of the Project:


· The Chemical Faculty of the Yerevan State University (YSU);
· The Institute of Fine Organic Chemistry of NAS of Armenia (IFOC).


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