Shagufta Naz1,2, Lina Tariq Al Kury3, Humaira Nadeem1, Fawad Ali Shah1, Aman Ullah1, Rehan Zafar Paracha4, Muhammad Imran5, Shupeng Li2. 1. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan. 2. State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People's Republic of China. 3. College of Natural and Health Sciences, Zayed University, Abu Dhabi, 49153, United Arab Emirates. 4. Research Center for Modeling & Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan. 5. Department of Pharmacy, IQRA University, Islamabad, 44000, Pakistan.
Abstract
Introduction: Several studies revealed that alcohol utilization impairs memory in adults; however, the underlying mechanism is still unclear. The production of inflammatory markers and reactive oxygen species (ROS) plays a major role in neurodegeneration, which leads to memory impairment. Therefore, targeting neuroinflammation and oxidative distress could be a useful strategy for abrogating the hallmarks of ethanol-induced neurodegeneration. Moreover, several studies have demonstrated multiple biological activities of thiazolidine derivatives including neuroprotection. Methods: In the current study, we synthesized ten (10) new thiazolidine-4-carboxylic acid derivatives (P1-P10), characterized their synthetic properties using proton nuclear magnetic resonance (1H-NMR) and carbon-13 NMR, and further investigated the neuroprotective potential of these compounds in an ethanol-induced neuroinflammation model. Results: Our results suggested altered levels of antioxidant enzymes associated with an elevated level of tumor necrosis factor-alpha (TNF-α), nuclear factor-κB (p-NF-κB), pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in ethanol-treated animals. Ethanol treatment also led to memory impairment in rats, as assessed by behavioral tests. To further support our notion, we performed molecular docking studies, and all synthetic compounds exhibited a good binding affinity with a fair bond formation with selected targets (NF-κB, TLR4, NLRP3, and COX-2). Discussion: Overall, our results revealed that these derivatives may be beneficial in reducing neuroinflammation by acting on different stages of inflammation. Moreover, P8 and P9 treatment attenuated the neuroinflammation, oxidative stress, and memory impairment caused by ethanol.
Introduction: Several studies revealed that alcohol utilization impairs memory in adults; however, the underlying mechanism is still unclear. The production of inflammatory markers and reactive oxygen species (ROS) plays a major role in neurodegeneration, which leads to memory impairment. Therefore, targeting neuroinflammation and oxidative distress could be a useful strategy for abrogating the hallmarks of ethanol-induced neurodegeneration. Moreover, several studies have demonstrated multiple biological activities of thiazolidine derivatives including neuroprotection. Methods: In the current study, we synthesized ten (10) new thiazolidine-4-carboxylic acid derivatives (P1-P10), characterized their synthetic properties using proton nuclear magnetic resonance (1H-NMR) and carbon-13 NMR, and further investigated the neuroprotective potential of these compounds in an ethanol-induced neuroinflammation model. Results: Our results suggested altered levels of antioxidant enzymes associated with an elevated level of tumor necrosis factor-alpha (TNF-α), nuclear factor-κB (p-NF-κB), pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in ethanol-treated animals. Ethanol treatment also led to memory impairment in rats, as assessed by behavioral tests. To further support our notion, we performed molecular docking studies, and all synthetic compounds exhibited a good binding affinity with a fair bond formation with selected targets (NF-κB, TLR4, NLRP3, and COX-2). Discussion: Overall, our results revealed that these derivatives may be beneficial in reducing neuroinflammation by acting on different stages of inflammation. Moreover, P8 and P9 treatment attenuated the neuroinflammation, oxidative stress, and memory impairment caused by ethanol.
Authors: I Apostolidis; K Liaras; A Geronikaki; D Hadjipavlou-Litina; A Gavalas; M Soković; J Glamočlija; A Ćirić Journal: Bioorg Med Chem Date: 2012-11-17 Impact factor: 3.641
Authors: Adriana M das Neves; Gabriele A Berwaldt; Cinara T Avila; Taís B Goulart; Bruna C Moreira; Taís P Ferreira; Mayara S P Soares; Nathalia S Pedra; Luiza Spohr; Anita A A dE Souza; Roselia M Spanevello; Wilson Cunico Journal: J Enzyme Inhib Med Chem Date: 2020-12 Impact factor: 5.051