Novel pharmaceutical composition of bradykinin potentiating penta peptide with beta-cyclodextrin: physical-chemical characterization and anti-hypertensive evaluation.
This work describes chemical properties and anti-hypertensive activity of an oral pharmaceutical formulation obtained from the complexation of beta-cyclodextrin (beta-CD) with bradykinin potentiating penta peptide (BPP-5a) founded in the Bothrops jararaca poison. Physical chemistry characterizations were recorded in order to investigate the intermolecular interactions between species in complex. Circular dichroism data indicated conformational changes of BPP-5a upon complexation with beta-CD. ROESY and theoretical calculations showed a selective approximation of triptophan moiety into cavity of beta-CD. Isothermal titration calorimetry data indicated an exothermic formation of the complex, which is accomplished by reduction of entropy. The anti-hypertensive activity of the BPP-5a/beta-CD complex has been evaluated in spontaneous hypertensive rats, showing better results than pure BPP-5a.
Denadai
Angelo M L
AM
Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
Ianzer
Danielle
D
Alcântara
Antônio Flávio de C
AF
Santoro
Marcelo M
MM
Santos
Cynthia F F
CF
Lula
Ivana Silva
IS
de Camargo
Antônio C M
AC
Faljoni-Alario
Adelaide
A
dos Santos
Robson A S
RA
Sinisterra
Rubén D
RD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D017837:Bothrops; D002151:Calorimetry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002942:Circular Dichroism; D006339:Heart Rate / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013816:Thermodynamics; D014757:Viper Venoms / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009842:Oligopeptides; D014757:Viper Venoms; D047392:beta-Cyclodextrins; C006791:bradykinin potentiating factors; C031215:betadex