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Antiviral and Antituberculosis Chemical Agents

#G-1619


Progenitors of Benzimidazole- and [B]-Annealed Benzothiophen- and/or Benzofuran-Containing Condensed Systems with Antiviral Activity and for the Struggle Against Tuberculosis (Synthesis and Wide Screening)

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
31.03.2008

Leading Institute
Georgian Technical University, Georgia, Tbilisi

Collaborators

  • Erweiterte Realschule Saarbrücken -Güdingen, Germany, Saarbrücken\nSouthern Research Institute, USA, AL, Birmingham

Project summary

Basic statistics on the modern global “tuberculosis problem” is well known: one third of the world’s population are considered to be infected; 6 millions of new cases are registered every year; TB accounts for 20% of adult and 6% of infantile early deaths. The ever-growing resistance of TB to medicines undoubtedly creates the demand for preparing new antitubercular remedies.

There also exists an equally urgent need in producing other new antiviral preparations.

For a successful accomplishment of the project, we believe that among a great number of compounds the bicyclic systems of benzothopene/benzofuran and benzimodazole are the promising ones in the struggle against tubeculosis.

This optimism is based on a wide range of physiological activity characterizing the derivatives of these simple cyclic systems. In particular, mention must be made of their ability to inhibit the virus spread, local anaesthesic and analgetic abilities. Alkyl-substituted benzimidazoles inhibit the spread of the flu virus (strain L4); they consist mainly of the vitamin B12, the structure of which contains 5,6-dimethylbenzimidazole as a fragment.

The research team headed by Prof. T. Khoshtaria, Dr. Sci. (chem.), has a great deal of experience in this area. For over 30 years they have been concerned with the problem of creating new medicinal preparations of a new generation. Prof. T. Khoshtaria together with his colleagues have synthesized the progenitors of new tetracyclic systems (pyrrocarbazoles, benzo[b]thiophenindoles, benzo[b]furoindoles, pyrroloacridines, pyrrolophenothiazines and their dioxides, pyrrolocumarines, pyrrolophenoxatines and many others). Among the derivatives of the above-listed tetracyclic systems, substances have been found, which, along with a high tubercularstatic activity, display a high activity against other viruses.

As the second bicyclic system we have chosen benthothiophene and benzofuran which in their turn are also characterized by a variety of physiological activity.

A few years ago the team began to cooperate with the American colleagues who suggested that pharmacological studies be carried out by them. About 150 compounds synthesized at the organic substance technology chair of Tbilisi Technical University have already been handed over to them. In in vitro experiments most of these compounds showed a high tuberculostatic activity and a relatively not so high antiviral activity. It is planned to hand over to the American collaborator more than 50 compounds for pharmacological tests.

For a successful fulfillment of the project it is necessary to accomplish the following three goals:

  1. to synthesize the progenitors of a new heterocyclic system of isomeric 1H-benzo[b]thiophen- and 1H-benzo[b]furobenzimidazoles.
  2. to sybthesize derivatives on their basis.
  3. to carry out pharmacological studies (broad screening) of the compounds synthesized by the

Georgian research team, including the progenitors.

The synthesis of tetracyclic systems with a benzimidazole fragment in the molecule will be carried out using the modication of the classical Phillips reaction, while isomeric 1,2-, 2,3- and 3,4- diamines of dibenzothiophen- and dibenzofuranes will be used as starting products. Remnants of semi- and thiocarbazides, hydrazides of nicotinic and isonicotinic acids, hydroxilamine, hydrazinhydrate, amino acides, alkylamines, sulfoacids and others will be chosen as substitutes, which, according to our data, favor an increase of the biological activity of the molecule on the whole.

All the synthesized compounds will be characterized by modern methods of investigation (IK, UV, PMR spectroscopy and mass-spectometry).

The persistent improvement of the methods of synthesis of starting products will make it possible to raise the yield of the target products to an optimal quantity.


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