Subhan Zakia, Ali Niaz, Ullah Abid, Ali Wajid, Nabi Muhammad, Shah Syed Wadood Ali
Department of Pharmacology, Institute of Pharmaceutical Sciences, Khyber Medical University, Hayatabad, Peshawar 25100, Khyber Pakhtunkhwa, Pakistan.
Department of Pharmacology, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia.
Biomolecules. 2025 Apr 23;15(5):611. doi: 10.3390/biom15050611.
Schiff bases synthesized in our laboratory have demonstrated pain-relieving effects through both peripheral and central nervous system pathways. Considering that centrally acting analgesics often affect the muscle tone of the gastrointestinal tract (GIT) and related deep internal organs, this study was conducted to examine potential relaxant effects on blood vessels and GIT smooth muscles. The possible relaxant effects of Schiff bases (SB1 and SB2) on isolated rabbit aortic strips were evaluated. The experiments involved assessing their impact on contractions induced by 80 mM potassium chloride (KCL) and 1 µM norepinephrine (NE). Norepinephrine concentration response curves (N. ECRCs) were constructed in the absence and presence of three different concentrations of SB1 and SB2, using N. ECRCs as a negative control. Terazosin served as a standard α1 receptor blocker. Docking studies were employed to validate the mechanism of action for SB1 and SB2. The study outcomes suggest that SB1 is more potent than SB2, demonstrating lower EC values for NE-induced contractions in intact (5.50 × 10 ± 2.23 M) and denuded (5.81 × 10 ± 3.80 M) aortae. For NE-induced contractions, SB1 showed percent relaxation values of 48% and 41% in intact and denuded aortae, respectively. In comparison, SB2 exhibited values of 82.5% and 74%, showing that SB1 is more efficacious than SB2. The rightward shift of N. ECRCs for both SB1 and SB2 confirms their inhibition of α1 receptors. Additive effects of SB1 and SB2 were seen in the presence of verapamil ( < 0.0001). Docking analysis revealed that the compounds can properly bind to the target receptor Gq 1D (P25100). Findings show that both Schiff base SB1 and SB2 produce significant ( < 0.05) vasorelaxation via the α1 receptor blocking mechanism.
我们实验室合成的席夫碱已通过外周和中枢神经系统途径显示出止痛效果。鉴于中枢性镇痛药常常会影响胃肠道（GIT）及相关深部内脏器官的肌张力，因此开展本研究以检测其对血管和GIT平滑肌的潜在舒张作用。评估了席夫碱（SB1和SB2）对离体兔主动脉条的可能舒张作用。实验包括评估它们对由80 mM氯化钾（KCL）和1 µM去甲肾上腺素（NE）诱导的收缩的影响。在不存在和存在三种不同浓度的SB1和SB2的情况下构建去甲肾上腺素浓度反应曲线（N. ECRCs），将N. ECRCs用作阴性对照。特拉唑嗪用作标准α1受体阻滞剂。采用对接研究来验证SB1和SB2的作用机制。研究结果表明，SB1比SB2更有效，在完整主动脉（5.50×10±2.23 M）和去内皮主动脉（5.81×10±3.80 M）中，SB1对NE诱导的收缩的EC值更低。对于NE诱导的收缩，SB1在完整主动脉和去内皮主动脉中的舒张百分比值分别为48%和41%。相比之下，SB2的值为82.5%和74%，表明SB1比SB2更有效。SB1和SB2的N. ECRCs右移证实了它们对α1受体的抑制作用。在维拉帕米存在的情况下观察到SB1和SB2的相加作用（<0.0001）。对接分析表明，这些化合物能够与靶受体Gq 1D（P25100）正确结合。研究结果表明，席夫碱SB1和SB2均通过α1受体阻断机制产生显著的（<0.05）血管舒张作用。
