Apiraksattayakul Setthawut, Pingaew Ratchanok, Prachayasittikul Veda, Ruankham Waralee, Jongwachirachai Papitcha, Songtawee Napat, Suwanjang Wilasinee, Tantimongcolwat Tanawut, Prachayasittikul Supaluk, Prachayasittikul Virapong, Phopin Kamonrat
Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand.
Front Mol Neurosci. 2022 Jul 22;15:890838. doi: 10.3389/fnmol.2022.890838. eCollection 2022.
Parkinson's disease (PD) is considered one of the health problems in the aging society. Due to the limitations of currently available drugs in preventing disease progression, the discovery of novel neuroprotective agents has been challenged. Sulfonamide and its derivatives were reported for several biological activities. Herein, a series of 17 bis-sulfonamide derivatives were initially tested for their neuroprotective potential and cytotoxicity against the 6-hydroxydopamine (6-OHDA)-induced neuronal death in SH-SY5Y cells. Subsequently, six compounds (i.e., , and ) were selected for investigations on underlying mechanisms. The data demonstrated that the pretreatment of selected compounds (5 μM) can significantly restore the level of cell viability, protect against mitochondrial membrane dysfunction, decrease the activity of lactate dehydrogenase (LDH), decrease the intracellular oxidative stress, and enhance the activity of NAD-dependent deacetylase sirtuin-1 (SIRT1). Molecular docking was also performed to support that these compounds could act as SIRT1 activators. In addition, pharmacokinetic and toxicity profile prediction was also conducted for guiding the potential development. Thus, the six neuroprotective bis-sulfonamides were highlighted as potential agents to be further developed for PD management.
帕金森病（PD）被认为是老龄化社会中的健康问题之一。由于目前可用药物在预防疾病进展方面存在局限性，新型神经保护剂的发现面临挑战。据报道，磺胺及其衍生物具有多种生物活性。在此，最初对一系列17种双磺胺衍生物针对6-羟基多巴胺（6-OHDA）诱导的SH-SY5Y细胞神经元死亡的神经保护潜力和细胞毒性进行了测试。随后，选择了六种化合物（即 、 和 ）对其潜在机制进行研究。数据表明，所选化合物（5 μM）预处理可显著恢复细胞活力水平，防止线粒体膜功能障碍，降低乳酸脱氢酶（LDH）活性，降低细胞内氧化应激，并增强NAD依赖性脱乙酰酶sirtuin-1（SIRT1）的活性。还进行了分子对接以支持这些化合物可作为SIRT1激活剂。此外，还进行了药代动力学和毒性概况预测以指导潜在的开发。因此，这六种神经保护双磺胺被视为有潜力进一步开发用于帕金森病治疗的药物。
