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Synthesis of a FTO inhibitor with anticonvulsant activity.

ABSTRACT: We describe the rationale for and the synthesis of a new class of compounds utilizing a modular approach that are designed to mimic ascorbic acid and to inhibit 2-oxoglutarate-dependent hydroxylases. Preliminary characterization of one of these compounds indicates in vivo anticonvulsant activity (6 Hz mouse model) at nontoxic doses, inhibition of the 2-oxoglutarate-dependent hydroxylase FTO, and expected increase in cellular N(6)-methyladenosine. This compound is also able to modulate various microRNA, an interesting result in light of the recent view that modulation of microRNAs may be useful for the treatment of CNS disease.

SUBMITTER: Zheng G

PROVIDER: S-EPMC4140589 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Synthesis of a FTO inhibitor with anticonvulsant activity.

Zheng Guanqun G Cox Thomas T Tribbey Leah L Wang Gloria Z GZ Iacoban Paulina P Booher Matthew E ME Gabriel Gregory J GJ Zhou Lu L Bae Nancy N Rowles Joie J He Chuan C Olsen Mark J MJ

ACS chemical neuroscience 20140605 8

We describe the rationale for and the synthesis of a new class of compounds utilizing a modular approach that are designed to mimic ascorbic acid and to inhibit 2-oxoglutarate-dependent hydroxylases. Preliminary characterization of one of these compounds indicates in vivo anticonvulsant activity (6 Hz mouse model) at nontoxic doses, inhibition of the 2-oxoglutarate-dependent hydroxylase FTO, and expected increase in cellular N(6)-methyladenosine. This compound is also able to modulate various mi ...[more]

PMID: 24834807

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