NANOQMEDProject funded by



PNCDI II: P4. "Partnerships in priority areas", D6. Biotechnology

Financing contract no.: 61-002/2007

Project no.: 1885/2007

Obtaining and characterization of new targeted-nanodrugs with naphthoquinonic active substance

 

Summary

NANOQMED is a multidisciplinary approach which includes the support brought by biotechnologies, coordinative chemistry, supramolecular chemistry and nanotechnologies for the development of new pharmaceutical products which can make up the basis of innovative therapies in human medicine (bio-active nanoproducts and nanomedicines, targeted-drugs with cellular specificity and reduced toxicity).

Quinones are substances whose molecule contains a benzoquinone, naphtoquinone, anthraquinone or phentanthrene nucleus. It is well known that organic substances with the main structure of 1,4 naphtoquinone which have in positions 2,3 functional groups containing sulfur or nitrogen as donor atoms, can act as ligands to obtain coordinative compounds (complex combinations) with plain-square structure of cis-platin complexes (compounds with high anti-tumor action). In NANOQMED, we proposed chemosynthesis of new complex combinations of transitional metals with new ligands (naphthoquinones), having mercapto, hydroxyl, amide and amino groups.

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Consortium

The Consortium consists of six participating entities: five from the academic area and one from industry (SME).

 

Grant holder (Coordinator - CO): The National Research and Development Institute for Cryogenics and Isotopic Technologies – ICSI Rm. Valcea

http://www.icsi.ro

  • Project manager: PhD. Radu Tamaian

  • Scientific officer: PhD. Violeta-Carolina Niculescu

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Partner 1 (P1): National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca

https://www.itim-cj.ro

  • P1 project responsible: PhD. Mircea Bogdan

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Partner 2 (P2): University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca

https://www.usamvcluj.ro

  • P2 project responsible: Prof. Ioan Marcus, DVM, PhD.

  • Scientific officer: Assoc. Prof. Bogdan Sevastre, DVM, PhD.

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Partner 3 (P3): Babeş-Bolyai University, Cluj-Napoca

https://www.ubbcluj.ro

  • P3 project responsible: Prof. Onuc Cozar, PhD.

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Partner 4 (P4): Technical University of Cluj-Napoca

https://www.utcluj.ro

  • P4 project responsible: Prof. Ioan Ardelean, PhD. Eng.

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Partner 5 (P5): SC Imofarm Impex SRL, Bucharest

  • P5 project responsible: Stefania Serban (Broscatean)

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Objectives

The aim of NANOQMED is the obtaining of new encapsulated bio-active products and/or immonoconjugates with a high degree of specificity and reduced toxicity. In a specific manner, through planned activities for deployment, it will be followed the achievement of a series of specific objectives:

  • identification of vegetal species, respectively of cellular lines capable of high biosynthesis of different natural naphtoquinones; extraction and purification;
  • synthesis of new coordinative compounds (complex combinations of naphtoquinones with transitional metallic ions),
  • characterisation and complete description of (bio)synthesised naphtoquinones and chemosynthesis of new coordinative compounds;
  • identification of natural naphtoquinones with the highest antitumoral potential and with the lowest general cytotoxicity by computer-aided drug design (CADD) techniques;
  • identification of the coordinative compounds with the highest antitumoural potential and with the lowest cytotoxicity and side- effects;
  • obtaining of immunoconjugates with naphtoquinonic payload;
  • obtaining of encapsulated coordinative compounds;
  • comparative testing of general cytotoxicity, cellular specificity and antitumoural effect of encapsulated coordinative compounds and immunoconjugates.

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Impact

Evolution of NANOQMED will be made according with the strict deontological rules of scientific research, the project manager will take into account all the measurements required to insure the respecting of these rules. In this meaning, all members of the research team, who signed the project proposal, will be engaged to respect these rules. The team members will be engaged to notify the project manager, in any occasion which will generate a contradiction with the research deontological rules, in this way the required measurements will be taken.

Environmental impact
We especially mention that the activities involved in this project do not suppose accomplishing of experiments on human subjects, and, also, there will be not accomplished activities which would generate an environmental pollution.

Social impact
At the end of the project, a better material base will be developed and there will be accumulated new technical knowledge in the metals and catalysts preparation domain, this fact leading to new work places creations dor young who wish to improve in special scientific media.

Economical impact
The main purpose of the proposed theme is finding a way for implementation the results in order to reduce the costs for obtaining metals from catalysts.
It is obvious that there will be made substantial efforts for elucidate the processes for obtaining target-drugs, as well as for nanostructures synthesis, but these efforts could be efficient only if they are based on a good knowledge of the mechanisms, which makes that these processes constitute a major theme for national and international scientific community.

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Budget (in RON)

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Project progress: dissemination, patents

 

Publications

 

B. Sevastre, I. Marcus, R. Tamaian, 2011, In silico identification of new antiproliferative compounds, inhibitors of matrix metalloproteinases. Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine, 68(1):334-343.

 

R. Tamaian, V. Niculescu, M. Anghel, 2010, In silico predictions for improving permeability properties of principal anticancer anthracyclines through structural modification. Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine, 67(1):329-336.

 

R. Tamaian, I. Marcus, V. Niculescu, B. Sevastre, M. Anghel, I. Prodan, 2010, Computational study of interspecies TOP2A similarities for further development of new double targeted therapeutic immunoconjugates. Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine, 67(1):373.

 

L.Szabó, V.Chiş, A.Pîrnău, N.Leopold, O.Cozar, Sz.Orosz, 2009, Spectroscopic and theoretical study of amlodipine besylate, Journal of Molecular Structure, 924–926:385-392, Show more, https://doi.org/10.1016/j.molstruc.2009.02.003.

 

V. Niculescu, R. Tamaian, N. Păun, A. Pîrnău, L. Szabó, 2009, Synthesis and spectral characterisation of a new metal complex with a bidentate ligand. Journal of Physics: Conference Series, 182(1):012030, doi:10.1088/1742-6596/182/1/012030.

 

R. Tamaian, B. Sevastre, V. Niculescu, I. Prodan, N. Păun, I. Marcus, 2009, Synthesis of New Kind of Naphthoquinonic Anti-Tumoural Compounds. Toxicity Tests. Romanian Journal of Biochemistry, 46(Suplementa):124-125.

 

R. Tamaian, N. Păun, V. Niculescu, A. Iordache, R. Vremeră, S. Broscătean, 2008, Antibiotic Effects of The Naphtoquinonic Derivative On Gram-Positive And Gram-Negative Germs. Chemické Listy, 102(15s):s479-481.

 

Manifestations:

 

The Second National Congress with International Participation of Integrative Medicines, 02 – 05 November 2011, Bucharest, Romania:

  •  R. Tamaian, V. Niculescu, M. Anghel – Antibody-Protein Comparative Automated Docking to Identify the Affinity of IMC-C225 for All its Known Targets. Abstracts, p. 91 (oral presentation)

 

The 16th ICIT International Conference “Progress in Cryogenics and Isotopes Separation”, 13 – 15 October 2010, Călimăneşti-Căciulata, România:

  •  I. Prodan, R. Manalachioae, B. Sevastre, V. Niculescu, N. Păun, R. Tamaian, I. Marcus – Antiproliferative Effect of 2-Cloro-3-Nicotinamido-1,4-Naphthoquinone, a Newly Synthesized Naphthoquinone. Proceedings, Ed. Conphys, ISSN 1582-2575, p. 140 (poster)

  •  R. Tamaian, V. Niculescu, M. Anghel – Computational Protonation Study of a New Synthetic Anticancer Naphthoquinone. Proceedings, Ed. Conphys, ISSN 1582-2575, p. 145 (oral presentation)

 

Processes in Isotopes and Molecules – PIM 2009, 24-26 September 2009, Cluj-Napoca, Romania:

  •  V. Niculescu, R. Tamaian, N. Păun, A. Pîrnău, L. Szabó – Synthesis and spectral characterisation of a new metal complex with a bidentate ligand, Book of Abstracts, p. 38 (poster T2-7)

 

3rd International Conference on Advanced Spectroscopies on Biomedical and Nanostructured Systems – NANOSPEC 2008, 7-10 September 2008, Cluj-Napoca, Romania:

  •  A. Pîrnău, L. Szabó, N. Leopold, O. Cozar, M. Bogdan, R. Tamaian, V. Chiș – DFT, Vibrational, NMR and ESR study of CU(II)-2-mercapto-3-nicotinamide-1,4-naphthoquinone molecular complex, NANOSPEC 2008 Abstracts, p. 78 (poster)

 

4th Central European Conference “Chemistry Towards Biology”, 08 – 11 September 2008 Dobogoko, Hungary:

  •  V. Niculescu, N. Păun, R. Tamaian – New high performance liquid chromatographic method for determination of 5-hydroxy-1,4-naphtoquinone (juglone) /Juglone`s natural biosynthesis highlight in fresh leaves from black walnut tree, Book of abstracts of 4th Central European Confrence Chemistry Towards Biology 2008, ISBN 978-963-9319-85-1, p. 113 (poster)

  •  N. Păun, V. Niculescu, R. Tamaian – An efficient method for determination of lawsone from Impatiens balsamina / Lawsone formation in Impatiens balsamina, Book of abstracts of 4th Central European Confrence Chemistry Towards Biology 2008, ISBN 978-963-9319-85-1, p. 117 (poster)

 

Patents:

 

Patent RO 127496 – Immunoconjugates with antiproliferative naphthalendione cytotoxic payload (authors: Radu Tamaian, Ioan Marcus, Violeta-Carolina Niculescu, Bogdan Sevastre, Iulia Luciana Popescu) published in BOPI (The Official Industrial Property Bulletin of Romania), No. 8/2019, Section Patents, 30-08-2019, p. 75 (RO)

 

Patent RO 127619 – Naphthalendione derivate used in tumoral growth control (authors: Violeta-Carolina Niculescu, Radu Tamaian, Ioan Marcus, Iulia Luciana Popescu, Bogdan Sevastre), published in BOPI (The Official Industrial Property Bulletin of Romania), No. 3/2018, Section Patents, 30-03-2018, p. 65 (RO)

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