Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 22 (24), 6908-17

Structural Analogues of the Natural Products Magnolol and Honokiol as Potent Allosteric Potentiators of GABA(A) Receptors

Affiliations

Structural Analogues of the Natural Products Magnolol and Honokiol as Potent Allosteric Potentiators of GABA(A) Receptors

Alexander Fuchs et al. Bioorg Med Chem.

Abstract

Biphenylic compounds related to the natural products magnolol and 4'-O-methylhonokiol were synthesized, evaluated and optimized as positive allosteric modulators (PAMs) of GABA(A) receptors. The most efficacious compounds were the magnolol analog 5-ethyl-5'-hexylbiphenyl-2,2'-diol (45) and the honokiol analogs 4'-methoxy-5-propylbiphenyl-2-ol (61), 5-butyl-4'-methoxybiphenyl-2-ol (62) and 5-hexyl-4'-methoxybiphenyl-2-ol (64), which showed a most powerful potentiation of GABA-induced currents (up to 20-fold at a GABA concentration of 3μM). They were found not to interfere with the allosteric sites occupied by known allosteric modulators, such as benzodiazepines and N-arachidonoylglycerol. These new PAMs will be useful as pharmacological tools and may have therapeutic potential for mono-therapy, or in combination, for example, with GABA(A) receptor agonists.

Keywords: Allosteric modulation; GABA(A) receptor; Honokiol; Ion channel; Magnolol; Medicinal plant; Natural product; Positive allosteric modulator (PAM); Synthesis.

Similar articles

See all similar articles

Cited by 4 PubMed Central articles

Publication types

MeSH terms

LinkOut - more resources

Feedback