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Stage 2020:

Metal-complexes (further studies)

Specific aims:
-> Study of the ability of potential drugs to inhibit enzymes that can be considered as possible targets in anticancer chemotherapy
-> Study of the encapsulation of the metal complexes into liposomes and their use for in vivo targeted delivery
-> Dissemination of the results

Deliverables: Stage 2020: Results of the enzyme inhibition tests; results of encapsulation of at least two complexes into liposomes; at least one full-paper submitted at an ISI journal; Scientific Report.

 

Scientific Report – Stage 3 (2020) – Metal-complexes (further studies)

Activities:
Activity 3.1. Study of the ability of potential drugs to inhibit enzymes that can be considered as possible targets in anticancer chemotherapy
Activity 3.2. Study of the encapsulation of the metal complexes into liposomes and their use for in vivo targeted delivery
Activity 3.3. Dissemination of the results

Expected results:

  • Results of the enzyme inhibition tests- achieved objective;
  • Results of encapsulation of at least two complexes into liposomes- achieved objective;
  • At least one full-paper submitted at an ISI journal -achieved objective;
  • Scientific Report - achieved objective.

Stage Results:

  • Results of the enzyme inhibition tests-  achieved objective

By using molecular docking studies, fluorescence and circular dichroism techniques, the ability of the obtained proligands and metal complexes in the protein binding (HSA-Human Serum Albumin) was highlighted. Molecular docking studies have shown the ability of ligands and metal complexes to inhibit Ribonucleotide Reductase (RNR), a key enzyme involved in the DNA metabolism.

Complex Docking
(Receptor@Ligand)

Contact No.

Contact Receptors (R2 RNR)

Eb
(kcal/mol)

Kd
(µM)

R2-RNR@L1

19

GLU233, GLY234, PHE237, SER238, PHE241, SER264, ARG265, GLU267, GLY268, CYS271, ASP272, CYS275, TYR324, PHE327, VAL328, ARG331, LEU332, GLU335, ASN346

-6.181

29.462

R2-RNR@C1

17

GLU233, GLY234, PHE237, SER238, PHE241, SER264, GLU267, GLY268, CYS271, ASP272, CYS275, TYR324,
PHE327, VAL328, ARG331, LEU332, GLU335

-8.393

0.704

  • Results of encapsulation of at least two complexes into liposomes- achieved objective

Two copper metal complexes were encapsulated in liposomes, which previously demonstrated the highest stability in buffer at different pH and proved to be biocompatible with normal cells and to show selectivity on cancer cells. Liposomal structures based on biopolymeric surfactants were obtained in the laboratory and previously tested for the encapsulation of some drugs.

The obtained liposomal formulations were characterized in terms of dimensionality and stability (by DLS) and also were tested in vivo on rats to determine the biodistribution at i.v. of liposomes by PET-MRI imaging and post-administration animal monitoring.

  • At least one full-paper submitted at an ISI journal - achieved objective

The results obtained in this stage of the project have been published in ISI journals as full paper  (1) and proceedings (2) and two book chapters were accepted:

  • Published articles:
  • Blends of sodium deoxycholate-based poly(ester ether)urethane ionomer and hydroxypropyl cellulose with mucosal adhesiveness, Doina Macocinschi, Daniela Filip, Bianca-Iulia Ciubotaru, Raluca Petronela Dumitriu, Mirela-Fernanda Zaltariov*, International Journal of Biological Macromolecules 162, 1262-1275 (2020).
  • Published Proceeding Articles:
  • Cytotoxicity evaluation of new ruthenium complexes, Mirela-Fernanda Zaltariov*, Maria Butnaru, Dragos Peptanariu, 2019 E-Health and Bioengineering Conference (EHB), ISBN – 978-1-7281-2603-6, INSPEC Accession Number:19300285, DOI: 10.1109/EHB47216.2019.8969978, pp.1-4, (2020).
  • Structural and cytotoxic evaluation of platinum(IV) complexes with biological active ligands, Mirela-Fernanda Zaltariov*, Mihaela Avadanei, Dragos Peptanariu, 2019 E-Health and Bioengineering Conference (EHB), ISBN – 978-1-7281-2603-6, INSPEC Accession Number: 19300423, DOI: 10.1109/EHB47216.2019.8970005, pp.1-4, (2020)
  • Mucoadhesive composites based on polyurethane/AgNPs for urinary catheter application, Bianca-Iulia Ciubotaru, Mirela-Fernanda Zaltariov*, Liliana Verestiuc, Daniela Filip, Doina Macocinschi, 2019 E-Health and Bioengineering Conference (EHB), ISBN – 978-1-7281-2603-6, INSPEC Accession Number: 19315184, DOI: 10.1109/EHB47216.2019.8970045, pp.1-4, (2020).
  • Book Chapters:
  • Bio-based polymers for liposomal drug formulations, Mirela-Fernanda Zaltariov*, Bianca-Iulia Ciubotaru, Marcela Savin, Daniela Filip, Doina Macocinschi, Chapter 4, in Applications of Biodegradable and Bio-Based Polymers for Human Health and a Cleaner Environment, Eds. I. Stoica, O. Mukbaniani, A. K. Haghi, Apple Academic Press, partnered with CRC Press, a member of the Taylor & Francis Group, ISBN: 9781771889766, (2020).
  • Metal complexes-based catalysts for oxidation reactions as new alternatives for catalytic processes in the production of bio-based polymers, Mirela-Fernanda Zaltariov*, Chapter 6, in Applications of Biodegradable and Bio-Based Polymers for Human Health and a Cleaner Environment, Eds. I. Stoica, O. Mukbaniani, A. K. Haghi, Apple Academic Press, partnered with CRC Press, a member of the Taylor & Francis Group, ISBN: 9781771889766, (2020).
  • Conferences:

The results of the research carried out in this stage of the project have been presented at international scientific events in the form of an Invited Conference:

  • Metal complexes in medicine: from drug design to therapeutic agents, Mirela-Fernanda Zaltariov, “International Congress of „Apollonia” University from Iași”-By promoting excellence, we prepare the future, Edition XXX, Iași, Romania, 27th of February – 1st of March (2020) – Invited Conference

 

  • Scientific Report- achieved objective.

All the objectives of this project stage, 2020, were met as planned achievement!

 

 

 

Stage 2018
Stage 2019
Stage 2020

ICMPP

UEFISCDI

MN

CNCS

 

 

 
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