In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, -ring, E-ring, F-ring, -atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound with a -isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound was preliminarily investigated. The result suggested that the cardiotonic effect of compound is related to calcium channels. Patch clamp technique confirmed that the compound had inhibitory effects on Ca1.2 and Ca3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 μM, respectively. Subsequently, the protective effect of on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound can alleviate CoCl-induced myocardial injury by alleviating calcium overload. These findings suggest that compound was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.

中文翻译：

---

具有强心和钙通道抑制活性的番茄碱衍生物的合成及生物学评价

我们在前期的研究中，对多种番茄碱型二萜生物碱进行了强心活性筛选，发现番茄碱具有中等强心作用。本研究通过对Lycoctonine骨架上的B环、β环、E环、F环、β原子进行修饰或成盐，合成了一系列结构多样的Lycoctonine。我们通过离体青蛙心脏评估了衍生物的强心活性，旨在鉴定一些具有显着增强心脏作用的化合物，其中具有α-异丁基的化合物成为最有前途的强心候选物。并对化合物的强心作用机制进行了初步探讨。结果提示该化合物的强心作用与钙通道有关。膜片钳技术证实该化合物对Ca1.2和Ca3.2有抑制作用，浓度为50 μM时抑制率分别为78.52%±2.26%和79.05%±1.59%。随后检测其对氯化钴诱导的H9c2细胞损伤的保护作用。此外，化合物还可以通过减轻钙超载来减轻CoCl诱导的心肌损伤。这些发现表明该化合物是一种衍生自番茄碱的新结构，可能作为治疗心力衰竭的新先导化合物。