Neuroprotective Properties of Bis-Sulfonamide Derivatives Against 6-OHDA-Induced Parkinson's Model via Sirtuin 1 Activity and in silico Pharmacokinetic Properties

Abstract

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., 2, 4, 11, 14, 15, and 17) 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, in silico 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.

Aminochalcones Attenuate Neuronal Cell Death under Oxidative Damage via Sirtuin 1 Activity

“…The structural difference between cocrystallized and redocked resveratrol molecules was determined by computing the root-mean-square deviation to validate the reliability of docking process. Following the docking process, the binding behavior and key binding interactions between the examined compounds and the target SIRT1 were revealed and illustrated using the Discovery Studio Visualizer 2016 (BIOVIA, Dassault Systèmes, CA, USA) …”

“…The assay relies on the conversion of lactate to pyruvate by the enzyme lactate dehydrogenase and further produces NADH as a product, giving rise to an increase in absorbance at 450 nm. The LDH activity was represented as a proportion to the control group …”

“…SIRT1 activity was measured with a microplate reader at excitation and emission wavelengths of 340 and 445 nm, respectively. The SIRT1 activity of cells was expressed as percentages relative to the control …”

“…The LDH activity was represented as a proportion to the control group. 81 Measurement of SIRT1 Activity. The SIRT1 assay kit (Cat.…”

Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease

“…One of the excellent inhibitors containing sulphonamide groups used for the treatment of Alzheimer’s disease, which is associated with butyrylcholinesterase (BuChE) inhibitory activity, was synthesized from previously marketed drugs containing sulphonamide derivatives and displayed excellent biological profiles at very low concentrations [ 15 , 16 ]. In the last few decades, sulphonamide derivatives have been extensively used as potent inhibitors against various diseases such as diabetes [ 17 , 18 ], psychosis [ 19 ], central nervous system (CNS) disorders [ 20 , 21 ], tumors [ 22 , 23 , 24 , 25 , 26 ] and different cancer treatments [ 27 , 28 ].Therefore, different heterocyclic moieties have been used by researchers in order to achieve fruitful results; in this regard, we synthesized and evaluated sulphonamide-containing aliphatic moieties and tested against α-Glucosidase, anti-urease, anti-bacterial and anti-fungal properties, which were found with excellent potential.…”