Denumire proiect: PD 474, Resurse Umane, CNCSIS

NOI COMPLECSI METALICI CU POSIBILA ACTIVITATE NUCLEZICA SI SOD MIMETICA. SINTEZA, ANALIZA STRUCTURALA, STUDII FIZICO-CHIMICE SI BIOLOGICE

Director: ef lucr. Dr. Adriana Hangan Perioada de derulare: iulie 2010 iulie 2012 Valoare contract: 300.000 RON Obiective
1. Sinteza, caracterizarea structurala si fizico-chimica a unor noi liganzi de tip sulfonamide heterociclice N-substituite. 2. Sinteza, caracterizarea structurala si fizico-chimica a unor complecsi ai liganzilor sulfonamidici cu ioni de Cu, Zn sau Ni cu posibila activitate nucleazica si/sau SOD mimetica. 3. Studiul activitatii nucleazice si a mecanismului de actiune pentru complecsii metalici nou sintetizati comparativ cu liganzii necoordinati. 4. Studiul activitatii SOD mimetice pentru complecii metalici obtinuti comparativ cu liganzii liberi. 5. Studii QSAR.Compararea pentru moleculele sintetizate (ligand-complex) a aranjamentului atomilor, distantelor dintre grupele reactive, conformatiilor posibile, continutului energetic, distributiei densitatii electronice, mobilitatii sarcinilor electrice in molecule permite evidentierea rolului gruparilor farmacofore din liganzi, ionilor metalici si structurii moleculei in ansamblu. 6. Selectionarea in vederea unor studii mai aprofundate a celor mai activi compusi in vederea introducerii in terapie ca potentiali agenti antivirali si antitumorali.

Etape. Activitati Anul 2010

1. Sinteza si caracterizarea liganzilor de tip sulfonamide N-substituite Sinteza sulfonamidelor heterociclice derivati de tiadiazol Elucidarea structurilor compusilor obtinuti si determinarea proprietatilor fizico-chimice 2. Stabilirea conditiilor de sinteza a combinatiilor complexe cu liganzii sulfonamidici obtinuti Studiul capacitatii de coordinare a ionilor metalici si proprietatilor chelato-formatoare ale sulfonamidelor nou sintetizate Studiul formarii si stabilitatii combinatiilor complexe in functie de natura liganzilor, ionilor metalici, raportul lor de combinare, solventi, temperatura, pH 3. Sinteza unor complecsi de Cu cu sulfonamide heterociclice derivati de tiadiazol

Anul 2011
1. Sinteza si caracterizarea complecsilor metalici cu liganzi de tip sulfonamide N-substituite Sinteza complecsilor de Cu, Zn, Ni cu sulfonamide heterociclice derivati de tiadiazol Analiza chimica elementala, caracterizarea structurala si fizico-chimica a complecsilor 2. Evaluarea activitatii nucleazice a complecsilor comparativ cu liganzii Stabilirea protocolului de studiu al activitatii nuclezice pentru liganzi si complecsii metalici Studiul propriu-zis al activitatii nucleazice al complecsilor metalici comparativ cu liganzii liberi Stabilirea modului in care complecsii metalici interactioneaza si degradeaza molecula de ADN (determinarea speciilor reactive de oxigen implicate in distrugerea moleculei de ADN)

Anul 2012
1. Evaluarea activitatii SOD mimetice a complecsilor comparativ cu liganzii Stabilirea protocolului de studiu al activitatii SOD mimetice al complecsilor metalici Evaluarea activitatii SOD mimetice a complecsilor comparativ cu liganzii 2. Studii QSAR -rolul unor grupari farmacofore pe o molecula suport potential bioactive; rolul ionilor metalici in actiunea biologica a sulfonamidelor; corelatia structurilor chimice cu activitatea biologica a compusilor

Rezultate estimate
1. Obtinerea, caracterizarea structurala si fizico-chimica de noi compusi cu activitate biologica specifica obtinerea de noi compusi heterociclici sulfonamidici, cu potential biolog, cu disponibilitate mare pentru coordinarea ionilor metalelor tranzitionale, cu proprietati chelato-formatoare elucidarea structurii lor si implicit a proprietatilor fizico-chimice sinteza si elucidarea structurii unor complecsi metalici cu liganzii sulfonamidici obtinuti, ce prezinta activitate nucleazica si/sau SOD-mimetica 2. Studiul activitatii biologice si elucidarea mecanismelor de actiune biologica a compusilor sintetizati evaluarea activitatii biologice comparativ liganzi-complecsi metalici, fiind vizate activitatea nucleazica si SOD-mimetica selectarea compusilor cei mai activi biologic in vederea continuarii studiilor in vivo pentru introducerea lor in terapie ca potentiali agenti antivirali sau antitumorali

Director proiect: ef lucr. Dr. Adriana Hangan Disciplina de Chimie Generala si Anorganica , Facultatea de Farmacie, Universitatea de Medicin i Farmacie "Iuliu Haieganu" ClujNapoca, 12 Ion Creanga RO-400010 Cluj-Napoca Romania Tel: 0264-593768 Mobil: 0722-413801 Email: acomsa6@yahoo.com

Projet title: PD 474, Resurse Umane, CNCSIS

NEW METALLIC COMPLEXES WITH POSSIBLE NUCLEASE AND SOD MIMETIC ACTIVITY. THE SYNTHESIS, THE STRUCTURAL ANALYSIS, PHYSICALCHEMICAL AND BIOLOGIC STUDIES

Projet manager: Lecturer PhD Adriana Hangan Perioada de derulare: july 2010 july 2012 Contract value: 300.000 RON Objectives
1. The synthesis, structural and physical-chemical characterization of a number of new Nsubstitute heterocyclic sulphonamide-type ligands. 2. The synthesis, structural and physical-chemical characterization of a number of complexes of sulphonamide ligands with Cu, Zn or Ni ions with possible nuclease and/or SOD-mimetic activity 3. The study of the nuclease activity and of the action mechanism for the newly synthesised metallic complexes in comparison with the non-coordinative ligands. 4. The study of the SOD-mimetic activity for the newly-created metallic complexes in comparison with the free ligands 5. The selection of the most active compounds for a more elaborate study of their therapeutic properties as potential antiviral and antitumour agents. 6. QSAR Studies .For the synthesised molecules (ligand complex) this relates to the comparison of the: atoms order, distances between reactive groups, possible conformations, energetic content, electronic density distribution and electric charges mobility which permits the identification of the pharmacophore classes role within ligands, metallic ions and the molecule structure as a whole.

Stages Year 2010

1. The synthesis and the characterization of the N-substituted sulphonamides used as ligands Synthesis of thiadiazolidic derivative sulfonamides. Structure assessment of the obtained compounds and determination of their physico-chemical properties. 2. The assessment of synthesis conditions of the metallic complexes with sulfonamidic ligands Study of coordination capacity of metal ions and the chelat-formation properties of the newly synthesized sulfonamides. Study of metallic complex formation and their stability in function of ligand and metallic ions nature, combination ratio, solvents, temperature, pH. 3. The synthesis of a new Cu(II) complexes with N-substituted sulfonamidic ligands

Year 2011
1. The synthesis and characterization of the metallic complexes with N-substituted sulfonamidic ligands Cu, Zn, Ni, complex synthesis with thiadiazolic sulfonamides. Elemental chemical analysis, structural and physico-chemical characterization of the obtained complexes. 2. The comparative assessment of the nuclease activity of compounds vs. Ligands Defining the study protocol of the nuclease activity for ligands and metallic complexes. The actual comparative study of the nuclease activity of the metallic compounds vs. free ligands Assessing the way metallic complexes interact and degrade the AND molecule (defining the reactive oxygen species responsible for the AND molecules degradation).

Year 2012
1. The comparative assessment of the SOD-mimetic activity of complexes vs. Ligands Defining the study protocol of the SOD-mimetic activity for the metallic complexes The actual comparative study of the SOD-mimetic activity of the complexes vs. ligands

2. QSAR studies - role assessment of certain pharmacophore groups on a support molecule with bioactive potential; role assessment of metallic ions in the biological activity of sulphonamides; Correlation of the chemical structure with the biological activity for these compounds

Estimated results
1. The synthesis, structural and physical-chemical characterization of new compounds with specific biologic activity the synthesis of new heterocyclic sulfonamide compounds, with biologic potential and the following characteristics: solubility in polar solvents, good coordination futures, capacity to generate chelats; the synthesis will be followed by structural and physical-chemical characterization synthesis and complete structural characterization of new metal complexes with the obtained sulfonamides as ligands; the structural features of the metal complexes make them good candidates as chemical nucleases and/or SOD-mimics

2. The biological activity study and the evaluation of the pharmacological mechanisms for the newly obtained compounds the evaluation of the metallic complexes biologic activity in comparison with the ligands; tests will be performed to evaluate the nuclease and SOD-mimetic activity screening of the active compounds for in vivo studies and potentially for subsequent clinical trials as antiviral and/or antitumor agents

Project manager: Lecturer PhD Adriana Hangan Inorganic Chemistry Departament, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haieganu" ClujNapoca, 12 Ion Creanga RO-400010 Cluj-Napoca Romania Phone: 0264-593768 Mobile: 0722-413801 Email: acomsa6@yahoo.com