Rational Design, Synthesis, and In Vitro Activity of Heterocyclic Gamma-Butyrobetaines as Potential Carnitine Acetyltransferase Inhibitors.

ABSTRACT: This study investigates heterocyclic gamma-butyrobetaine (GBB) analogs as metabolic modulators through an integrated approach involving rational design, molecular docking, synthesis, and in vitro evaluation. The compounds synthesized demonstrated promising inhibitory potential toward carnitine acetyltransferase (CAT) and presumably other enzymes within the carnitine transferase family, with IC₅₀ values ranging from 2.24 to 43.6 mM. Notably, some compounds demonstrated superior activity to the reference drug Meldonium (IC₅₀ = 11.39 mM). A substantial outcome of the study that might serve as a foundation for future optimization and synthesis of more potent compounds was that a bulky, hydrophobic substituent at the gamma position enhances inhibitory activity, whereas est

SUBMITTER: Stoyanova S 

PROVIDER: S-EPMC11820905 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature