Synthesis and anticholinesterase activity of huperzine A analogues containing phenol and catechol replacements for the pyridone ring

G Campiani; A P Kozikowski; S Wang; L Ming; V Nacci; A Saxena; B P Doctor

doi:10.1016/s0960-894x(98)00229-7

Synthesis and anticholinesterase activity of huperzine A analogues containing phenol and catechol replacements for the pyridone ring

Bioorg Med Chem Lett. 1998 Jun 2;8(11):1413-8. doi: 10.1016/s0960-894x(98)00229-7.

Authors

G Campiani¹, A P Kozikowski, S Wang, L Ming, V Nacci, A Saxena, B P Doctor

Affiliation

¹ Dipartimento Farmaco Chimico Tecnologico, Siena University, Italy.

PMID: 9871776
DOI: 10.1016/s0960-894x(98)00229-7

Abstract

Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alkaloids
Animals
Catalysis
Catechols / chemical synthesis
Catechols / pharmacology
Cattle
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / pharmacology
Crystallography, X-Ray
Hydrogen Bonding
Models, Molecular
Palladium
Phenols / chemical synthesis
Phenols / pharmacology
Pyridones / chemistry
Sesquiterpenes / chemical synthesis*
Sesquiterpenes / pharmacology
Structure-Activity Relationship

Substances

Alkaloids
Catechols
Cholinesterase Inhibitors
Phenols
Pyridones
Sesquiterpenes
huperzine A
Palladium