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Stage 2019:

Metal-complexes of modified indolo[2,3-c]quinolines and new indolo[3,2- d]benzazepines

Specific aims:
-> Synthesis of metal-based indolo[2,3-c]quinolines and new indolo[3,2-d]benzazepines
-> Purification and characterization of the obtained metal complexes
-> Studies on solution equilibria and hydrolytic stability of the proligands and metal complexes in biological environments
-> Study of antiproliferative activity of proligands and metal complexes in several cancer cell lines and normal cells
-> Dissemination of the results

Deliverables: Stage 2019: At least four well-defined metal complexes based on new indolo[2,3-c]quinolines and indolo[3,2-d]benazepines containing metal-binding sites; results of antiproliferative activity assays for four proligands and four metal complexes; at least one research article submitted at an ISI journal; Scientific Report.


Scientific Report – Stage 2 (2019) – Metal-complexes of modified indolo[2,3-c]quinolines and new indolo[3,2-d]benzazepines

Activities Stage 2:
Activity 2.1. Synthesis of metal-based indolo[2,3-c]quinolines and new indolo[3,2-d]benzazepines
Activity 2.2. Purification and characterization of the obtained metal complexes
Activity 2.3. Studies on solution equilibria and hydrolytic stability of the proligands and metal complexes in biological environments
Activity 2.4. Study of antiproliferative activity of proligands and metal complexes in several cancer cell lines and normal cells
Activity 2.5. Dissemination of the results

Expected results:

  • At least four metal complexes based on indoloquinoline and indolobenzazepine proligands full characterized- achieved objective;
  • results of antiproliferative activity assays for four proligands and four metal complexes- achieved objective;
  • at least one research article submitted at an ISI journal -achieved objective;
  • Scientific Report-achieved objective.

Stage Results:

  • At least four metal complexes based on indoloquinoline and indolobenzazepine proligands full characterized - achieved objective

Based on the proligands synthesized in stage 1, metallic complexes of copper(II), zinc(II), platinum(IV) and ruthenium(III) were obtained, which were structurally characterized by IR, UV-vis spectroscopy, ESI-MS and where possible, by single crystal X-ray diffraction. We also studied the complexation capacity of the obtained proligands by UV-Vis spectroscopy, using the Hildebran-Benesi and Job’s methods to determine the complexation constant and the stoichiometric ratio proligand: metal.
 

  • results of antiproliferative activity assays for four proligands and four metal complexes- achieved objective

For the obtained proligands and metal complexes, cytocompatibility tests were performed on normal cells (Normal Human Dermal Fibroblasts (NHDF)) and cytotoxicity tests on several tumor lines: Human osteosarcoma (HOS), breast cancer (MCF7), human melanoma (MEWO), hepatocarcinoma (HEPG2) and Human colonic adenocarcinoma (SW480) by MTT method and microscopic evaluation of cells in contact with test compounds.


  • at least one research article submitted at an ISI journal -achieved objective
  • Published articles:
  • Ruthenium(II) complexes with cytotoxic activity embedded in hydroxypropyl methylcellulose/sodium alginate mucoadhesive hydrogels, Mirela-Fernanda Zaltariov*, Bianca-Iulia Ciubotaru, Liliana Verestiuc, Dragos Peptanariu, Doina Macocinschi, Daniela Filip, Cellulose Chemistry and Technology,  53(9-10), 869-878 (2019);
  • Micellar and rheological properties of some sodium deoxycholate-based poly(ester ether)urethane ionomer biomaterials in N,N-dimethylformamide solutions, Daniela Filip, Doina Macocinschi, Stelian Vlad, Constanţa Ibănescu, Maricel Danu, Mirela Fernanda Zaltariov*, Journal of Molecular Liquids, 285, 451-458 (2019);
  • Conferences:

The results of the research carried out in this stage of the project have been presented at international and national scientific events in the form of an Invited Conference (1), oral presentations (5), posters (3).

  • Metal-based anticancer drugs, Mirela-Fernanda Zaltariov, International Congress of „Apollonia” University from Iași "By promoting excellence, we prepare the future" Edition XXIX, 28 February - 3 March 2019, Iași, Romania- Invited Conference
  • Cytotoxicity evaluation of new ruthenium complexes, Mirela-Fernanda Zaltariov, Maria Butnaru, Dragos Peptanariu, 7th IEEE International Conference on e-Health and Bioengineering - EHB 2019, 21-23 November 2019-oral communication;
  • Mucoadhesive composites based on polyurethane/AgNPs for urinary catheter application, Bianca-Iulia Ciubotaru, Mirela-Fernanda Zaltariov, Liliana Verestiuc, Daniela Filip, Doina Macocinschi, 7th IEEE International Conference on e-Health and Bioengineering - EHB 2019, 21-23 November 2019-oral communication;
  • Selective cytotoxic activity of some metal complexes, Mirela-Fernanda Zaltariov, Vladimir Arion, “Zilele Spitalului Clinic C.F. Iasi” - Performanta Stiintei – Stiinta Performantei 22-27 October (2019) – oral communication;
  • New insights into antitumor activity of new metal complexes based on thiosemicarbazone and indoloquinoline proligands, Mirela-Fernanda Zaltariov, 13th Romanian International Symposium of Cosmetic and Flavor Products (RISCFP) – “Cosmetology-The essence of beauty and wellness”, June 4-7 2019, Iasi, Romania – oral communication;
  • Metal complexes as antitumor agents: design, structure-activity relationship and perspective, Mirela-Fernanda Zaltariov, 11th International Conference on Materials Science and Engineering – BraMat 2019, March 13-16, Brasov, Romania – oral communication;
  • Structural and cytotoxic evaluation of platinum(IV) complexes with biological active ligands, Mirela-Fernanda Zaltariov, Mihaela Avadanei, Dragos Peptanariu, 7th IEEE International Conference on e-Health and Bioengineering - EHB 2019, 21-23 November 2019-poster;
  • Metal complexes with antitumor activity, Mirela-Fernanda Zaltariov, Vladimir Arion, Faculty of Chemistry Conference „IasiCHEM 2019, Ediţia a III-a” 31 October - 1 November (2019) – poster;
  • Antioxidant activity and biosynthetic process of spirulina platensis of a new ferrocenyl Schiff Base, Alexandru Stoica, Mirela-Fernanda Zaltariov, 9th International EuroAliment Symposium, Galati, Romania 5–6 September (2019) – poster;
  • The results of this stage were updated on the web page of the project: http://www.icmpp.ro/metdrug
  • Scientific Report- achieved objective.

 

All the objectives of this project stage, 2019, were met as planned achievement!

 

Stage 2018
Stage 2019
Stage 2020

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