Proiect PN II IDEI Contract Nr 248/2007

SCRINING VIRTUAL PENTRU LIGANZII RECEPTORILOR ADRENERGICI


Coordonator: Institutul de Chimie Timisoara al Academiei Romane

Director de proiect: Dr. chim. Maria MRACEC



Rezumat

Receptorii adrenergici controleaza o serie de procese fiziologice esentiale, ca excitarea sau inhibarea muschilor netezi in diferite tesuturi si organe, excitarea miocardului, modularea proceselor sistemului nervos central, reglarea proceselor metabolice si endocrine. Azi sunt utilizate clinic o serie de medicamente (agonisti sau antagonisti ai receptorilor alfa- sau beta-adrenergici) pentru tratarea astmului, bronsitelor, spasmelor bronhice, hipertensiunii arteriale, hipertensiunii oculare, congestiei nazale, socului anafilactic, hiperplaziei benigne a prostatei, aritmiei cardiace, tahicardiei, infarctului miocardic acut, anghinei pectorale, migrenelor. Desi medicamentele actuale sunt considerate printre cele mai bune posibile la ora actuala, ele au o serie de efecte secundare datorate selectivitatii scazute fata de diferiti receptori. De aceea cercetarile actuale experimentale sau teoretice din domeniul proiectarii medicamentului sunt indreptate spre obtinerea unor liganzi cat mai puternici si mai selectivi pe un anumit receptor. Proiectul de fata propune un studiu de scrining virtual in clasa receptorilor adrenergici.

Principalele obiective ale proiectului:

Echipa de cercetare
Nume si prenume Anul nasterii Titlul didactic stiintific Doctorat Anul sustinerii tezei Burse Durata Finantare
Liliana Ostopovici - Halip 1978 Asistent cercetare Da 2007 Univ. New Mexico, Dept.of Biocomputing, SUA 15.09.07-15.09.08 (postdoc) UNM
Ramona Florentina Rad - Curpan 1978 Asistent cercetare Da 2007 Univ. New Mexico, Dept.of Biocomputing, SUA 15.09.07-15.09.08 (postdoc) UNM
Ana Borota 1979 Asistent cercetare Doctorand - Univ. New Mexico, Dept.of Biocomputing, SUA 9.07.08-5.09.08 (stagiu de perfectionare) Grant CNCSIS PN-II
Alexandra Gruia 1982 Asistent cercetare Doctorand - Univ. New Mexico, Dept.of Biocomputing, SUA 9.07.08-5.09.08 (stagiu de perfectionare) Grant CNCSIS PN-II

Publicatii

  1. 3D homology model of the alpha2a adrenergic receptor subtype, Liliana Halip, Ana Borota, Maria Mracec, Ramona Curpan, Alexandra Gruia, Mircea Mracec, Rev. Roum. Chim. 2009, 54 (2) 157-161
  2. Conformational Analysis of Dexmedetomidine, Maria Mracec, Alexandra Gruia, Ana Borota, Ramona Curpan, Liliana Halip, Mircea Mracec, Rev. Chim. (Buc.) 2009, 60, 488-490
  3. QSAR study of a series of quinoline derivatives active on the alpha2 adrenergic receptor subtypes, Maria Mracec, Alexandra Gruia, Ana Borota, Ramona Rad, Liliana Ostopovici, Mircea Mracec, Rev. Roum. Chim. 54, 651-657

Manifestari stiintifice

  1. Conformational analysis of dexmedetomidine, a high potent agonist of the alpha2a adrenergic receptor, Maria Mracec, Alexandra Gruia, Ana Borota, Ramona Curpan, Liliana Halip, M. Mracec, Internat. Conf. Phys. Chem., ROMPHYSCHEM-13, sept 3-5, 2008, Abstracts, p.39
  2. Electronic and molecular structure of dexmedetomidine, agonist of the alpha2 adrenergic receptor subtypes, Maria Mracec, Ana Borota, Alexandra Gruia, Liliana Halip, Ramona Curpan, M. Mracec, Internat. Conf. Phys. Chem., ROMPHYSCHEM-13, sept 3-5, 2008, Abstracts, p.39
  3. Electronic and molecular structure of brimonidine, agonist of the alpha2 adrenergic receptor subtypes, Maria Mracec, Ana Borota, Alexandra Gruia, Ramona Curpan, Liliana Halip, M. Mracec, Internat. Conf. Phys. Chem., ROMPHYSCHEM-13, sept 3-5, 2008, Abstracts, p.40
  4. QSAR study of a series of quinoline derivatives active on the alpha2 adrenergic receptor subtypes, Maria Mracec, Alexandra Gruia, Ana Borota, Ramona Curpan, Liliana Halip, M. Mracec, Internat. Conf. Phys. Chem., ROMPHYSCHEM-13, sept 3-5, 2008, Abstracts, p.40
  5. 3D-homology model of the alpha2a adrenergic receptor and preliminary results of some agonists docking, Liliana Halip, Ana Borota, Alexandra Gruia, Ramona Curpan, Maria Mracec, M. Mracec, Internat. Conf. Phys. Chem., ROMPHYSCHEM-13, sept 3-5, 2008, Abstracts, p.34

Rezumat al lucrarilor efectuate in 2008 in cadrul proiectului conform obiectivelor prevazute.


anul 2009

Rezumat al lucrarilor efectuate in 2009 in cadrul proiectului conform obiectivelor prevazute.


Echipa de cercetare (actualizare)
Nume si prenume Anul nasterii Titlul didactic stiintific Doctorat Anul sustinerii tezei Burse Durata Finantare
Liliana Ostopovici - Halip 1978 Cercetator Stiintific Da 2007 Univ. New Mexico, Dept.of Biocomputing, SUA 15.01.09-15.04.09 (postdoc) UNM
Ramona Florentina Rad - Curpan 1978 Cercetator Stiintific Da 2007 Univ. New Mexico, Dept.of Biocomputing, SUA 15.01.09-15.07.09 (postdoc) UNM
Ana Borota 1979 Asistent cercetare Doctorand - - - -
Alexandra Gruia 1982 Asistent cercetare Doctorand - - - -


Manifestari stiintifice
"11th Edition of Timisoara's Academic Days, Chemical physics and computational chemistry section" Timisoara, 28-29 mai 2009

  1. Ana Borota, Liliana Halip, Alexandra Gruia, Ramona Curpan, Maria Mracec and Mircea Mracec, Homology model of alpha2B adrenergic receptor: validation by agonist docking studies, Chemistry Symposium Abstracts, pag 96, ISBN: 978-973-52-0630-7 (prezentare orala)
  2. Liliana Ostopovici Halip, Ana Borota, Ramona Rad Curpan and Maria Mracec, Similarities and differences between the binding sites of the alpha2 adrenoceptor subtypes, Chemistry Symposium Abstracts, pag 91, ISBN: 978-973-52-0630-7 (poster)
  3. Ramona Rad Curpan, Liliana Ostopovici Halip, Alexandra Gruia, Ana Borota, Maria Mracec, Mircea Mracec, Comparative ab initio study of dexmedetomidine conformers in neutral and protonated states, Chemistry Symposium Abstracts, pag 89, ISBN: 978-973-52-0630-7, (poster)
  4. Ana Borota, Liliana Halip, Alexandra Gruia, Ramona Rad Curpan, Maria Mracec and Mircea Mracec, QSAR study of quinoline derivatives active on alpha2 adrenoceptors, Chemistry Symposium Abstracts, pag 90, ISBN: 978-973-52-0630-7, (poster)

Lucrari stiintifice
Sunt în curs de evaluare sau de publicare la diferite reviste lucrarile:
  1. Ana Borota, Liliana Ostopovici Halip, Alexandra Gruia, Maria Mracec, Ramona Rad Curpan, Mircea Mracec, A QSAR study using the MTD method and DRAGON descriptors for selective ligands of alpha2C adrenoceptor, Eur. J. Med. Chem., 2010 (in curs de revizuire)
  2. Liliana Ostopovici Halip, Ana Borota, Alexandra Gruia, Maria Mracec, Ramona Rad Curpan, Mircea Mracec, 3D homology model of the alpha2B adrenergic receptor subtype, Rev. Roum. Chim., 2010, 55, 343-348
  3. Liliana Ostopovici Halip, Ramona Curpan, Ana Borota, Maria Mracec, Cristian G. Bologa, Structural determinants of the alpha2 adrenoceptor subtype selectivity, J. Mol. Graph. Model (in curs de evaluare)