PROJECT CODE PN3-P3
Grant number 8BM/28/06/2016
Project title: New synergic biomaterials for anticancer therapy (SYNERG)
FUNDING AUTHORITY – THE NATIONAL AUTHORITY FOR SCIENTIFIC RESEARCH OF ROMANIA – UEFISCDI
Budget:39200 RON
BILATERAL COOPERATION ROMANIA – SOUTH AFRICA REASERCH PROJECTS
(http://uefiscdi.gov.ro/articole/3685/Cooperare-bilaterala-Romania–Africa-de-Sud–Competitia-2014.html)
 

 Project Summary

The project continues and develops support contract research addressing a dual strategy of combining original synthesized pyrazole derivatives with extracts standardized in flavonoids in order to obtain mixtures with synergistic mechanism of action, useful in anticancer therapy. The original extracts will be prepared in accordance with current regulations from poorly exploited species belonging to indigenous flora. We  will obtain new combinations from  plant extracts and pyrazole compounds designed to operate on a wider range of cellular targets. These mixtures are converted into biomaterials based on intermolecular hydrogen bonds. Getting these materials is intended to improve stability and increase the bioavailability of flavonoids phytocomplexes.

The project contributes to the development of innovative materials and processes and their use in medicine.

Romanian partner will prepare plant extracts, biomaterials and pharmaceutical form and the partner from South Africa will conduct investigations on cancer cell lines regarding the effects of the extracts and biomaterials on cytotoxicity, apoptosis induction, dose-effect relations, and demonstrate the mechanisms of action at the cellular level.

 STAGE I (2016)

Budget: 10000 lei

Objectives

Capitalization the potential of indigenous flora for new therapeutic approaches in the treatment of cancer. Evaluation of anticancer effect of plant extracts. Extending the applicability of original compounds obtained under the support contract. Toxicity evaluation of plant extracts.

The activities planned for this phase of the contract were:

1. Obtaining and chemical characterization of plant extracts (P1) – Part I
2. Evaluation of anticancer activity of plant extracts and chemical compounds (P2) – Part I
3. Evaluation of acute and chronic toxicity of plant extracts and chemical compounds (P1) – Part I

Results 

All activities under the work plan have been completed, obtaining the following results:

1. Obtaining of total plant extracts (43) – experimental model for obtaining total dry extracts.
2. Chemical characterization of the extracts with the identification of representative compounds or main classes of compounds.
3. Evaluation of biological activity (cytotoxicity) on 3 cancer cell lines (HeLa, MCF7 and Caco-2) of some of these extracts.
4. Assessment of toxicity on invertebrate organisms – Artemia salina and Daphnia magna of some of these extracts.

A. The results of this research stage were capitalized by the following articles published/ submitted for publicationin ISI journals:

1. Oana Cristina Seremet, Florica Barbuceanu, Floriana Elvira, Ionica, Denisa Marilena Margina, Claudia Maria Gutu, Octavian Tudorel Olaru, Mihaela Ilie, Veaceslav Gonciar, Simona Negres, Cornel Chirita. Oral toxicrty study of certain plant extracts containing pyrrolizidine alkaloid. Romanian Journal of Morphologyand Embryology. Accepted for publication.
2. Seremet OC, Gutu CM, Nitulescu GM, Ilie M, Margina D, Zbarcea CE, Negres S, Olaru OT. Toxicity of extracts from medicinal plants containing pyrrolizidine alkaloids in Daphnia magna and Artemia salina. Chemosphere. Submittedfor publication; under evaluation.

B. The results of this research stage were capitalized by the following presentations at international congresses:

Indexed in Web of Science (ISI)

1. Olaru, O.; Nitulescu, G. M.; Margina, D.; Spies, L.; Koekemoer, T.; van de Venter, M.; Tzatzarakis, M.; Tsatsakis, A. Antitumor and toxicological research on some ranunculosides containing plants. 52st Congress of the European-Societies-of-Toxicology (EUROTOX), September 4th-7th 2016, Seville, Spain, Toxicology Letters, 258(2), S74. ISSN: 0378-4274 poster.
2. Olaru, O.; Nitulescu, G.; Spinu, C.; Potolea, I.; Pirvu, O.; Ilie, M.; Nitulescu, G. M. The assessment of Ficaria verna acute toxicity by two alternative methods: Daphnia magna and Physella acuta bioassays. 52st Congress of the European-Societies-of-Toxicology (EUROTOX), September 4th-7th 2016, Seville, Spain,, Toxicology Letters, 258(2), S66. ISSN: 0378-4274.poster.
3. Olaru, O. T.; Pirvu, O. M.; Spinu, C. E.; Potolea, I. M.; Nagoda, E.; Dinu-Pirvu, C.; Comanescu, P. C.; Babeanu, N.; Ilie, M.; Nitulescu, G. M. HPTLC determination of β-aescin in extracts from five species of Aesculus (Sapindaceae). International Symposium: Priorities of Chemistry for a Suitable Development – PRIOCHEM, 27-28 oct. 2016, Bucuresti, Volum de rezumate, p. 52, ISSN: 2285-8334.poster.
4. Olaru, O. T.; Arama, C.; Van de Venter, M.; Spies, L.; Koekemoer, T.; Dinu, M.; Ancuceanu, R.; Istudor, V.; Nitulescu, G. M. Simultaneous determination of phenolic acids and flavonoids in extracts from three Fallopia species by HPLC. International Symposium: Priorities of Chemistry for a Suitable Development – PRIOCHEM, 27-28 oct. 2016, Bucharest, Volum de rezumate, p. 53, ISSN: 2285-8334.poster.)

C. The results of this research stage were capitalized by the following presentations at international of national congresses:

1. Olaru OT, Venables L, Nitulescu G, Koekemoer T, Nitulescu GM, van de Venter M. Antiproliferative assay of Euphorbia species extracts on human cancer cell lines. Maedica – Journal of Clinical Medicine, Volume 11, Supplement, 2016. p. 13. ISSN: 2501-6903. (Congresul UMF Carol Davila 2016, 2-4 iunie 2016, București – oral presentation –work awarded with diploma of excellenceat Young Investigator Award)
2. Olaru OT (1), Spies L (2), Nitulescu G, Koekemoer T, Swanepoel B, Nutilescu GM, van de Venter M. Anticancer evaluation of Hemerocallis fulva L. (Xanthorrhoeaceae). Abstracts of the 16^th National Congress of Pharmacy from Romania – Pharmacy Interdisciplinary Center for Life Sciences, 28^th September – 1^st October 2016, Bucharest, p. 192, ISSN 2537–2823.
3. Olaru OT, Spînu CE, Potolea IM, Pîrvu OM, Făgăraş DL, Voinicu IB, Nitulescu GM. The obtaining of some extracts from plants containing aristolochic acid and their acute toxicity evaluation. Abstracts of the 16^th National Congress of Pharmacy from Romania – Pharmacy Interdisciplinary Center for Life Sciences, 28^th September – 1^st October 2016, Bucharest, p. 197, ISSN 2537–2823.poster.

•  CV_Alexandru_Cotoban;
• CV_Andrei_Dumitru_Margulescu;
• CV_Lucia_Stefania_Magda;
•  CV_Roxana_Cristina_Rimbas;
•  CV_Ruxandra_Dragoi_Antunes_Galrinho;
• Memoriu_stiintific_Andrei_Dumitru_Margulescu