Publication: Unraveling Network Pharmacology-Based Therapeutics of Anthranilate Sulfonamides via Sirtuins/FOXO3a Cascade in Alzheimer's Disease
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Issued Date
2026-02-01
Resource Type
ISSN
00223042
eISSN
14714159
Scopus ID
2-s2.0-105030632661
Pubmed ID
41714304
Journal Title
Journal of Neurochemistry
Volume
170
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Neurochemistry Vol.170 No.2 (2026)
Suggested Citation
Ruankham W., Prachayasittikul V., Pingaew R., Jeungprasopsuk W., Tantimongcolwat T., Prachayasittikul V., Prachayasittikul S., Phopin K. Unraveling Network Pharmacology-Based Therapeutics of Anthranilate Sulfonamides via Sirtuins/FOXO3a Cascade in Alzheimer's Disease. Journal of Neurochemistry Vol.170 No.2 (2026). doi:10.1111/jnc.70377 Retrieved from: https://hdl.handle.net/20.500.14740/55328
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Abstract
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 (SA1–4) and therapeutic targets are not clearly clarified. To unravel the neuroprotective roles and underlying mechanisms of SA1–4 against oxidative injury and healthy longevity crosstalk, a combination of in vitro experiments, in silico modeling, and network pharmacology was employed. Pretreatment with SA1–4 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 SA1–4 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 SA1–4 and key targets-regulated SIRTs in neurodegeneration, including non-amyloidogenic cascade, tau phosphorylation, calcium homeostasis, insulin-mediated glucose uptake, and neuroinflammation. Therefore, SA1–4 exert promising multi-target therapeutic strategies against oxidative damage, potentially offering alternative anti-Alzheimer candidates for further clinical neurodegenerative and anti-aging therapeutics. (Figure presented.).