Objective
The developing scientific collaboration in the complementary topic research on natural compounds of plant origin between Uzbek and Georgian phytochemical Institutes (NIS teams) and four laboratories from INTAS (France and Belgium) has led these organizations to the proposed project.
The main objective of the project consists in helping to Uzbek and Georgian Institutes to select some potentially antitumoral natural compounds from the promising endemic plants of these countries and containing alkaloids and saponins. Among the compounds, the most active representatives will be discovered for their possible application in human medicine in the field of cancerology.
For the realization of these objectives, the following investigations will be carried out :
- Selection of plants, preparation of crude extracts, isolation of pure alkaloids and saponins.
This part of work will be carried out by Uzbek Institute on alkaloids and Georgian Institute on saponins by bibliographic searches, jointly with the Laboratory in Marseilles;
- Structural determination of pure alkaloids and saponins. Analytical analysis.
The identification of pure compounds and structure determination of new of them by chemical and spectral methods will be done in Tashkent and Tbilisi. Structures of complex new compounds will be elucidated in Marseilles and in the group of Dr G. Massiot (France).
Analytical analysis by HPLC will be made in Marseilles.
The Laboratory in Marseilles will organized a training of scientists from NIS teams on purification with using the modern instruments and methods
- Cytotoxicity : screening on crude extracts and pure alkaloids and saponins, mechanism of action.
These studies will be done in the Laboratories of Liège (Belgium) and Clermont-Ferrand (France). The in vitro cytotoxicity will be evaluated on two complementary type of tests, using human cancer cell lines. The most cytotoxic extracts (IC50 >> 100 µg/ml) and pure compounds will be selected. For the selected compounds the in vitro mechanism of action will be studied;
- Specific cytotoxicity
The Laboratories of Liège and Clermont Ferrand will realize different tests including : intercalation in DNA, inhibition of topoisomerases, apoptose, action on the proteins DNA, RNA synthesis, ultrastructural modifications, induction of genus (p. 53, p. 21 NFKB, Bax), evaluation of reduced glutathion pool, evaluation of metabolic inactivation or "sur-activation by human hepatocytes, modification of the mitochondrial potential;
- Associations alkaloids/saponins
Such associations will be studied to improve the activity of alkaloids.
All biological investigations will be checked by both INTAS teams of Pharmacologists.
Expected results on the projects :
- Intensification of the collaboration between 6 organizations, belonging to INTAS and NIS countries;
- Isolation of new natural compounds of plant origin;
- Development of some potentially antitumoral compounds for possible application of them in human medicine.
All participants will decide if the results will be :
- Protected by joint patent;
- Proposed to pharmaceutical industry;
- Submitted to publication in international scientific journals.
The management, supervision of the progress and co-ordination of the work will be held by the co-ordinator, using reports at the end of each step, an every year meeting and a training of NIS scientists in the laboratories of INTAS countries.
Topic(s)
Call for proposal
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13385 Marseille cedex 5
France