Benzothiazole Derivatives as Dual Modulators of PGE2 and GABAergic Signaling in Skeletal Muscle
Year: 2026
Type: preprint
Abstract: Benzothiazoles are attractive scaffolds for small-molecule modulators of neuronal signaling. However, their impact on skeletal muscle and GABAergic pathways remains poorly understood. We synthesized a focused library of benzothiazole derivatives via oxidative electrophilic substitution and profiled their activity in C2C12 skeletal muscle cells, assessing cytotoxicity, proliferation, myogenic differentiation, and GABA-related signaling using cell-based assays, real-time PCR, and transcriptomics. Omics-guided analyses revealed that selected benzothiazole derivatives differentially modulate myogenic differentiation and prostaglandin E2, and simultaneously bidirectionally regulate GABAergic and glutamatergic signaling genes, including synaptic subunits and transporters. Notably, a lead derivative downregulated Gabrg2, a GABA-A receptor subunit implicated in epilepsy and other disorders of inhibitory synapses, highlighting a potential link between skeletal muscle signaling and neuropsychiatric disease. These findings position benzothiazole derivatives as candidate modulators of GABAergic signaling with translational potential for conditions involving dysfunctional inhibitory synapses.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: An Inverted Nikon A1R Laser Scanning Confocal Microscope, Regulation of Store-Operated Calcium Entry During Muscle Aging, OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING, MG29 function in regulation of Store-Operated Calcium Entry during Muscle Aging, UT Southwestern Center for Translational Medicine, Semiconductor Biomaterials to Speed Bone Healing: A Bioengineering-Driven Approach, G968121717
OpenAlex ID: W7163417467