Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
Nonlinear and Fiber Optics, Institute of Electronics, Bulgarian Academy of Science, 72 Tzarigradsko Chaussee, 1784 Sofia, Bulgaria.
Molecules. 2024 Aug 11;29(16):3804. doi: 10.3390/molecules29163804.
The synthesized compound 1-(2-chlorophenyl) 6-7-dimethoxy-3-methyl-3,4-dihydroisoquinoline (DIQ) was investigated as a biological agent. Its potential to affect muscle contractility was predicted through in silico PASS analysis. Based on the in silico analysis, its capabilities were experimentally investigated. The study aimed to investigate the effects of DIQ on the ex vivo spontaneous contractile activity (CA) of smooth muscle (SM) tissue. DIQ was observed to reduce the strength of Ca-dependent contractions in SM preparations (SMP), possibly by increasing cytosolic Ca levels through the activation of a voltage-gated L-type Ca channel. DIQ potently affected calcium currents by modulating the function of muscarinic acetylcholine receptors (mAChRs) and 5-hydroxytryptamine (5-HT) receptors at a concentration of 50 μM. Immunohistochemical tests showed a 47% reduction in 5-HT and 5-HT receptor activity in SM cells and neurons in the myenteric plexus (MP), further confirming the effects of DIQ. Furthermore, a significant inhibition of neuronal activity was observed when the compound was co-administered with 5-HT to SM tissues. The conducted experiments confirm the ability of the isoquinoline analog to act as a physiologically active molecule to control muscle contractility and related physiological processes.
合成化合物 1-(2-氯苯基)-6-7-二甲氧基-3-甲基-3,4-二氢异喹啉（DIQ）被研究为一种生物制剂。通过 PASS 分析的计算机模拟预测其影响肌肉收缩力的潜力。基于计算机模拟分析，对其进行了实验研究。该研究旨在研究 DIQ 对平滑肌（SM）组织离体自发性收缩活性（CA）的影响。观察到 DIQ 降低了 SM 制剂（SMP）中 Ca 依赖性收缩的强度，可能是通过激活电压门控 L 型 Ca 通道增加细胞浆 Ca 水平。DIQ 通过调节毒蕈碱乙酰胆碱受体（mAChRs）和 5-羟色胺（5-HT）受体的功能，在 50 μM 的浓度下强烈影响钙电流。免疫组织化学测试显示 5-HT 和 5-HT 受体在肌间神经丛（MP）中的 SM 细胞和神经元中的活性降低了 47%，进一步证实了 DIQ 的作用。此外，当该化合物与 5-HT 共同给予 SM 组织时，观察到神经元活性显著抑制。进行的实验证实了异喹啉类似物作为一种生理活性分子控制肌肉收缩力和相关生理过程的能力。
