Two L-nucleosides, L-30-amino-30-deoxy-N6-dimethyladenosine (L-30-ADMdA) 1, previously synthesized in our laboratory, and the novel L-30-amino-30-deoxy-N6-methyladenosine-50-N-methyluronamide (L-30-AM-MECA) 2 were evaluated in an ischemia/reperfusion model on Langendorff perfused mouse heart. L-30-ADMdA 1 was found to enhance functional recovery from ischemia (32.2 ± 3.7 cm H2O/s % rate pressure product, compared to 21.3 ± 1.4 for the control and 30.7 ± 3.4 for adenosine) and increase the time to onset of ischemic contracture (14.5 ± 0.9 min, compared to 10.5 ± 1.0 min for the control and 13.6 ± 0.6 min for adenosine) comparable to adenosine. Consistent with the functional recovery data, decreased infarction area was seen in the case of 1 (19.1 ± 8.4, compared to 40.5 ± 7.2% for the control and 11.5 ± 2.1% for adenosine). In contrast, L-30-AM-MECA 2 did not show significant functional recovery, increased onset of contracture, nor decreased infarction area compared to control. Unlike adenosine, neither 1 nor 2 induced cardiac standstill in mouse heart.
|Titolo:||Novel L-adenosine analogs as cardioprotective agents|
|Autori interni:||CHIACCHIO, MARIA ASSUNTA ROSSELLA|
|Data di pubblicazione:||2009|
|Rivista:||BIOORGANIC & MEDICINAL CHEMISTRY|
|Appare nelle tipologie:||1.1 Articolo in rivista|