TY - JOUR
T1 - Synthesis of a new inotropic steroid derivative and its relationship with log P, π, Rm, Vm, Pc and St
AU - Lauro, Figueroa Valverde
AU - Francisco, Díaz Cedillo
AU - María, Lopez Ramos
AU - Elodia, García Cervera
AU - Quijano-Ascencio, K. A.
AU - Cordoba-Vazquez, J. C.
PY - 2011
Y1 - 2011
N2 - In this work, a new inotropic steroid derivative was synthesized. The route involved preparation of furosemide-pregnenolone derivative by the reaction of furosemide with pregnenolone-succinate-ethylenediamine conjugate using a carbodiimide as catalyst. The biological activity of furosemide-pregnenolone and pregnenolone-succinate-ethylenediamine was evaluated in isolated rat hearts using Langendonff model. To delineate the structural chemical requirements of furosemide-pregnenolone as inotropic agent, other parameters such as the physicochemical descriptors log P, π, Rm, Vm, P c and St were calculated. The results showed that the furosemide-pregnenolone derivative significantly increase the perfusion pressure (p = 0.006), coronary resistance (p = 0.005) and intracellular calcium (1.35 × 10-3 to 2.70 × 10-3 mM) in isolated heart. Additionally, other data indicate that values of log P, π, Rm, Vm, Pc and St are high in the furosemidepregnenolone in comparison with pregnenolone-succinate- ethylenediamine. These data suggest that functional groups involved in the structure of furosemide-pregnenolone are specific for their positive inotropic activity.
AB - In this work, a new inotropic steroid derivative was synthesized. The route involved preparation of furosemide-pregnenolone derivative by the reaction of furosemide with pregnenolone-succinate-ethylenediamine conjugate using a carbodiimide as catalyst. The biological activity of furosemide-pregnenolone and pregnenolone-succinate-ethylenediamine was evaluated in isolated rat hearts using Langendonff model. To delineate the structural chemical requirements of furosemide-pregnenolone as inotropic agent, other parameters such as the physicochemical descriptors log P, π, Rm, Vm, P c and St were calculated. The results showed that the furosemide-pregnenolone derivative significantly increase the perfusion pressure (p = 0.006), coronary resistance (p = 0.005) and intracellular calcium (1.35 × 10-3 to 2.70 × 10-3 mM) in isolated heart. Additionally, other data indicate that values of log P, π, Rm, Vm, Pc and St are high in the furosemidepregnenolone in comparison with pregnenolone-succinate- ethylenediamine. These data suggest that functional groups involved in the structure of furosemide-pregnenolone are specific for their positive inotropic activity.
KW - Descriptors
KW - Langendonff model
KW - Physicochemical
KW - Pregnenolone
UR - http://www.scopus.com/inward/record.url?scp=79952169377&partnerID=8YFLogxK
M3 - Artículo
SN - 0970-7077
VL - 23
SP - 1599
EP - 1604
JO - Asian Journal of Chemistry
JF - Asian Journal of Chemistry
IS - 4
ER -