Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Campeche, Camp., México.
Facultad de Nutrición, Universidad Veracruzana, Médicos y Odontologos, Unidad del Bosque Xalapa Veracruz, México.
Drug Res (Stuttg). 2023 Jun;73(5):263-270. doi: 10.1055/a-1995-6351. Epub 2023 Mar 1.
Some studies show that some Dibenzo derivatives can produce changes in the cardiovascular system; however, its molecular mechanism is not very clear.
The objective of this investigation was to evaluate the inotropic activity of ten Dibenzo derivatives (compounds 1 to 10) on either perfusion pressure or left ventricular pressure.
Biological activity produced by the Dibenzo derivatives on either perfusion pressure or coronary resistance was evaluated using an isolated rat heart. In addition, the molecular mechanism of biological activity produced by compound 4 (Dibenzo[b,e]thiophene-11(6H)-one) on left ventricular pressure was determined using both Bay-k8644 and nifedipine as pharmacological tools in an isolated rat heart model.
The results showed that Dibenzo[b,e]thiophene-11(6H)-one increases perfusion pressure and coronary resistance at a dose of 0.001 nM. Besides, other data display that Dibenzo[b,e]thiophene-11(6H)-one increases left ventricular pressure in a dose-dependent manner (0.001 to 100 nM) and this effect was similar to biological activity produced by Bay-k8644 drug on left ventricular pressure. However, the effect exerted by Dibenzo[b,e]thiophene-11(6H)-one was inhibited in the presence of nifedipine at a dose of 1 nM.
All these data suggest that Dibenzo[b,e]thiophene-11(6H)-one increase left ventricular pressure through calcium channel activation. In this way, Dibenzo[b,e]thiophene-11(6H)-one could be a good candidate as positive inotropic agent to heart failure.
一些研究表明，一些二苯并衍生物会引起心血管系统的变化；然而，其分子机制尚不清楚。
本研究旨在评估十种二苯并衍生物（化合物 1 至 10）对灌流压或左心室压的变力活性。
采用离体大鼠心脏评估二苯并衍生物对灌流压或冠状动脉阻力的生物活性。此外，还使用 Bay-k8644 和硝苯地平作为药理学工具，在离体大鼠心脏模型中确定化合物 4（二苯并[b，e]噻吩-11（6H）-酮）对左心室压产生的生物学活性的分子机制。
结果表明，二苯并[b，e]噻吩-11（6H）-酮在 0.001 nM 剂量下增加灌流压和冠状动脉阻力。此外，其他数据显示，二苯并[b，e]噻吩-11（6H）-酮以剂量依赖性方式增加左心室压（0.001 至 100 nM），这种作用类似于 Bay-k8644 药物对左心室压的生物活性。然而，在 1 nM 剂量的硝苯地平存在下，二苯并[b，e]噻吩-11（6H）-酮的作用被抑制。
所有这些数据表明，二苯并[b，e]噻吩-11（6H）-酮通过激活钙通道增加左心室压。通过这种方式，二苯并[b，e]噻吩-11（6H）-酮可以作为心力衰竭的正性肌力药物的候选药物。
