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#G-1496


Progenitors of Indole- and [b]-Annealed Benzofurocontaning Condensed Systems for The Struggle against Coronary Insufficiency, Tuberculosis, AIDS and Tumoral Diseases (Synthesis and Wide Screening)

Tech Area / Field

  • MED-DRG/Drug Discovery/Medicine
  • BIO-CHM/Biochemistry/Biotechnology

Status
3 Approved without Funding

Registration date
19.01.2007

Leading Institute
Georgian Technical University, Georgia, Tbilisi

Collaborators

  • Southern Research Institute, USA, AL, Birmingham

Project summary

The basic statistics of the present-day global "tuberculosis problem" is well known: one-third of the global population is considered infected; there appear 6 million new cases each year; tuberculosis accounts for 20% of adult deaths and 6% of infant deaths. The growing resistance of tuberculosis to drugs certainly highlights the need for new antitubercular preparations.

Equally urgent is the need for new antiviral agents.

The authors of the Project propose to combine the expertise of the scientists of Georgia and the USA to develop a new generation of biologically active compounds, especially those with tuberculostatic and antiviral activity, based on the original indole-containing condensed systems - isomeric dioxodihydro-1H-benzo[b]furoindoles and unsubstituted 1H-benzo[b]furoindoles.

The strategy based on literature precedents is substantiated by the fact that the combination of two pharmacologically active bicyclic systems in one molecule can produce an increase of the biological activity of the molecule as a whole, which will widen the range of its pharmacological action.

In the present study, the basic bicyclic system is indole.

Since the nature of the second bicyclic system has been found to play an important role in pharmacological investigations of tetracyclic systems, benzo[b]furane has been chosen as a bicyclic partner.

The team of researchers headed by Prof. T.Khoshtaria has more than 30 years of expertise and experience in the synthesis and study of the biological activity of new condensed tetracyclic systems and their derivatives whose molecule contains – along with an indole fragment – various bicyclic systems.

The results of their investigations are in good agreement with literature data. Substances with a high tuberculostatic and antiviral activity have been found among the heterocyclic compounds which they have synthesized.

A few years ago they started collaboration with the colleagues from the USA, who carried out a preliminary screening of over 50 compounds synthesized at the Heterocyclic Compounds Synthesis Laboratory of TGU. Experiments in vitro showed that many of them possess a high antitubercular activity against the Mycobacterium tuberculosis (H37Rv) strain, while several had a high antiviral activity against the IVA (H1N1), IVA (H3N2) and IVB strains.

Of 12 possible isomers of the initial tetracyclic system of dibenzofurane, the team succeeded in synthesizing all of them: 6 unsubstituted 1H-benzo[b]furoindoles and
6 dioxodihydro-1H-furoindoles which are progenitors of new heterocyclic systems.

The above-mentioned heterocyclic systems were received by the authors of the proposed project for the first time by the methods based on the classical reactions of E. Fischer and Sandmeier.

The present Project intends to improve the process of synthesis of the target products – unsubstituted isomeric 1H-benzo[b]furoindoles as well as of their derivatives.

For the fulfillment of the projects it is necessary to solve the following tasks:

  1. To synthesize isomeric dioxodihydro-1H-benzo[b]furoindoles and biologically active compounds based on them;
  2. To synthesize and modify the method of obtaining unsubstituted 1H-benzo[b]furoindoles and biologically active derivatives based on them.
  3. To carry out a pharmacological study (wide screening) of the synthesized compounds in respect to Mycobacterium tuberculosis strains (H37Rv), and the Flu A and Flu B viruses.


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