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: Şef 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: Şef lucr. Dr. Adriana Hangan

Disciplina de Chimie Generala si Anorganica ,

Facultatea de Farmacie,

Universitatea de Medicină şi Farmacie "Iuliu Haţieganu" Cluj–Napoca,

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, PHYSICAL-

CHEMICAL 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 N-

substitute 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 ion’s 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 molecule’s

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 Haţieganu" Cluj–Napoca,

12 Ion Creanga

RO-400010 Cluj-Napoca

Romania

Phone: 0264-593768

Mobile: 0722-413801

Email: acomsa6@yahoo.com