Kamonrat Phopin

Parkinson’s disease (PD) is the second most common age-related motor neurodegenerative disease (ND) that has critically posed a global health burden since the 18th century. There is also no full therapy for the clinical syndrome, nor halts the progression of the disease. This study aimed to investigate multidisciplinary potentials of the acetamidosulfonamides (1–16) in PD via systematic biology-based in vitro, in silico, and network pharmacology assessments. The biological effects of the synthetic compounds, especially 8, 13, 14, and 16, provided potent neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced Parkinsonian SH-SY5Y model through the modulation of antioxidant defenses, antiapoptotic signaling, mitochondrial balance, and the regulation of both acetylcholinesterase (AChE) and sirtuin 1 (SIRT1). Molecular docking confirmed that these synthetic compounds interact favorably with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE, as well as the active binding pocket of SIRT1. The network pharmacology and target enrichment analysis also revealed a close correlation with APP, MAOA, MAOB, SLC6A3, and DRD1, governing the regulation of neurotransmitters. In summary, this research highlights four acetamidosulfonamides as promising candidates to be further developed as multitarget anti-PD agents for PD prevention and management.

Insulin-like growth factor-binding protein 7 (IGFBP-7) is a potential biomarker for early diagnosis of acute kidney injury (AKI). Herein, we have developed a novel label-free electrochemical immunosensor based on the self-assembly of 6-(ferrocenyl)hexanethiol (Fc) and antibody-coupled L-cysteine on the gold nanoparticle-modified electrode (Ab/Fc-Au/SPCE) for sensitive detection of IGFBP-7 in urine. Fc was directly embedded on the electrode surface to serve as an intrinsic redox signal for the IGFBP-7 immunosensor. The binding of IGFBP-7 target to the immobilized antibody resulted in a decrease in the peak current of the differential pulse voltammetry (DPV) measurement. The Ab/Fc-Au/SPCE exhibited a good linear DPV response to IGFBP-7 concentrations ranging from 0.0001 to 100.0 pg mL^-1, with a limit of detection (LOD) of 0.07 pg mL^-1. Validation using spiked artificial urines showed recovery rates in a range of 79.8 to 109.3%. The proposed immunosensor demonstrated good specificity and long-term stability, which are crucial properties for biosensor implementation. Importantly, the electrochemical IGFBP-7 immunosensor can function without the need for external redox agents, requiring only simple steps of sample incubation and subsequent PBS buffer rinsing. Our findings demonstrate a promising potential of Ab/Fc-Au/SPCE immunosensor as a Point-of-Care Testing (POCT) device for rapid detection of IGFBP-7 in early AKI diagnosis.

Sulfonamide‐based compounds have been a clinically attractive scaffold for drug development and proven as antioxidant and antimicrobial agents, but their pharmacological derivatives containing anthranilates (SA 1–4 ) and therapeutic targets are not clearly clarified. To unravel the neuroprotective roles and underlying mechanisms of SA 1–4 against oxidative injury and healthy longevity crosstalk, a combination of in vitro experiments, in silico modeling, and network pharmacology was employed. Pretreatment with SA 1–4 in human neuronal SH‐SY5Y cells significantly regulated sirtuins (SIRTs)/forkhead box class O 3a (FOXO3a)‐mediated longevity signaling pathway via targeting endogenous antioxidant enzymes (i.e., superoxide dismutase 2 [SOD2] and catalase [CAT]), apoptotic cascades (i.e., Bcl‐2‐associated X‐protein [BAX] and B‐cell lymphoma‐2 [BCL‐2]), mitochondrial balance, and ultimately led to the neuronal rescue. Molecular docking simulations support the possibility of the SA 1–4 modulatory effect within the active binding site of SIRT1. Importantly, in silico predictions of pharmacokinetic profiles suggested that the synthetic compounds possessed preferable drug‐like properties, good oral bioavailability, and safety profiles. Network pharmacology also revealed the involvement of SA 1–4 and key targets‐regulated SIRTs in neurodegeneration, including non‐amyloidogenic cascade, tau phosphorylation, calcium homeostasis, insulin‐mediated glucose uptake, and neuroinflammation. Therefore, SA 1–4 exert promising multi‐target therapeutic strategies against oxidative damage, potentially offering alternative anti‐Alzheimer candidates for further clinical neurodegenerative and anti‐aging therapeutics. image

Due to the irreversible destructive nature of Parkinson’s disease (PD), the development of neuroprotective agents is crucially needed as its current medications are only symptomatic treatments. 1,2,3-Triazole is an attractive scaffold for the discovery of novel therapeutic agents due to its versatile biological activities. This study aimed to investigate the neuroprotective effect of 1,2,3-triazole-based sulfonamides against 6-hydroxydopamine (6-OHDA)-induced neuronal SH-SY5Y cells. The effects of triazole derivatives on cell viability, intracellular reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) leakage, and sirtuin 1 (SIRT1) activity were evaluated in the 6-OHDA-induced cells. The results indicated that six compounds (2a – 5a and 3b – 4b) exhibited promising neuroprotective potentials due to their abilities to decrease intracellular ROS production and LDH leakage, along with increasing SIRT1 activity. Molecular docking was also conducted to reveal possible binding modes and interactions against the SIRT1 target through the key interacting residues of ILE223, LEU215, and PRO212. In silico pharmacokinetic prediction indicated that these compounds are drug-like molecules, possibly further developed as oral neuroprotective drugs. A set of possible PD-related targets of these six compounds is also highlighted for further investigations. Cytotoxicity assays in normal lung MRC-5 fibroblasts showed relatively high IC50 values, indicating low toxicity and favorable safety profiles. In summary, these six 1,2,3-triazole-based sulfonamides might potentially be neuroprotective agents for further PD therapeutic development.

The development of aptasensor to detect hazardous herbicide, glyphosate (GLY), is proposed in this study. An amino-labeled aptamer was immobilized onto the carboxylic group of 4-aminophenylacetic acid (CMA)- modified screen-printed carbon electrode (SPCE) as a sensing strategy. The alterations of electrode surface were characterized by scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR) spectroscopy, Raman spectroscopy, contact angle analysis, and electrochemical studies using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Furthermore, the analytical performances were mainly investigated by EIS study. The proposed aptasensor demonstrated a good linear response ranging from 10.0 nM to 10.0 μM with a correlation coefficient square (R²) of 0.9986. A calculated limit of detection (LOD) of 0.0515 μM and sensitivity of 0.564 Ω μM^-1cm^-2 were obtained. A good selectivity against various interferences including glycine, captan, diquat, and paraquat was also achieved. Moreover, the recovery rates in spiked tap water, orange juice, and strawberries showed satisfactory outcomes in the range of 87.8 to 120.3 %. Hence, the proposed aptasensor could serve as a promising technique for glyphosate detection in order to prevent its excessive accumulation in environments and commodities, thus ensuring safety for human livelihood and healthiness.

A set of 1,4-naphthoquinone (1,4-NQ) derivatives possesses various pharmaceutical activities. Among them, a synthetic 2-(4-methoxyanilino)naphthalene-1,4-dione (MN) is found to be non-cytotoxic to the normal MRC-5 cells and prevent neuronal SH-SY5Y cell damage. To explore the underlying interaction mechanism of MN in the circulatory system, in silico and multi-spectroscopic techniques were employed to investigate the complex of human serum albumin (HSA) and MN. The interaction between HSA and MN exhibited static fluorescence with a potential dynamic mechanism, as K_sv×10⁵ (M⁻¹) decreased with increasing temperatures. Thermodynamic parameters and molecular dynamics (MD) simulations indicated a stable and spontaneous binding process driven by hydrophobic interactions and endothermic characteristics. Both circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy analyses revealed that MN induced conformational changes in HSA, affecting α-helix, β-turn, β-sheet, and random coil components, thereby altering the secondary structure of HSA. Competitive binding and molecular docking showed that MN preferentially binds to subdomain IIA in site I of HSA with the lowest binding affinity (‒7.15 kcal/mol), though it also has some affinities for subdomains IB and IIIA in site III and II, respectively. Additionally, the esterase activity of HSA showed no significant changes in the presence of MN. Understanding the binding interaction between MN and HSA provides valuable insights for further investigating the pharmacodynamic mechanism of MN and its potential applications in the area of medicinal chemistry.

Herbicides are a group of substances used to control undesired vegetation in both agricultural and non-agricultural settings. They are recorded as the most consumed class among other pesticides, reaching nearly two million tons worldwide. Despite their effectiveness in weed control, the extensive utilization of herbicides has raised concerns regarding adverse effects on human health. However, comprehensive reviews addressing herbicide-related human health risks remain limited. This work aims to compile scientific evidence and possible underlying mechanisms to emphasize the hazards that need to be acknowledged, as well as to explore novel strategies for minimizing the impact on human health. Scientific data on herbicide-related human health risks, including human-related data and non-human experimental research, were retrieved from databases such as PubMed, Scopus, and Google Scholar. Pre-determined eligibility criteria were applied to select the final studies. A narrative summary of evidence-based human incidence and laboratory experiments is presented to organize and highlight key findings. This indicates the life-threatening nature of herbicide exposure in humans, ranging from acute toxicity to the development of chronic diseases at any stage of life. Herbicidal chemicals can harm individuals through various pathways, especially by inducing oxidative stress or directly disrupting molecular and cellular processes. Despite some conflicting findings, effective mitigation strategies are urgently needed to promote a safer society and protect human well-being.

Novel thiazole sulfonamides revealed capabilities against 6-OHDA-induced neuronal damage via SIRT1 activity. Thus, these neuroprotective thiazole sulfonamides could be promising candidates for the further development of effective PD therapy.