Preparation, anticholinesterase activity and molecular docking of new lupane derivatives.
A set of twenty one lupane derivatives (2-22) was prepared from the natural triterpenoid calenduladiol (1) by transformations on the hydroxyl groups at C-3 and C-16, and also on the isopropenyl moiety. The derivatives were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and some structure-activity relationships were outlined with the aid of enzyme kinetic studies and docking modelization. The most active compound resulted to be 3,16,30-trioxolup-20(29)-ene (22), with an IC50 value of 21.5μM for butyrylcholinesterase, which revealed a selective inhibitor profile towards this enzyme.
INQUISUR-CONICET, Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, B8000CPB Bahía Blanca, Argentina.
María Julia
MJ
Castro
UMYMFOR (CONICET-UBA), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina.
Victoria
V
Richmond
Instituto Universitario de Bio-Orgánica (CIBICAN), Av. Astrofísico Francisco Sánchez 2, 38206, Departamento de Química Orgánica, Universidad de La Laguna, Tenerife, Spain.
Carmen
C
Romero
UMYMFOR (CONICET-UBA), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina.
Marta S
MS
Maier
Instituto Universitario de Bio-Orgánica (CIBICAN), Av. Astrofísico Francisco Sánchez 2, 38206, Departamento de Química Orgánica, Universidad de La Laguna, Tenerife, Spain.
Ana
A
Estévez-Braun
Instituto Universitario de Bio-Orgánica (CIBICAN), Av. Astrofísico Francisco Sánchez 2, 38206, Departamento de Química Orgánica, Universidad de La Laguna, Tenerife, Spain.
Angel G
AG
Ravelo
INQUISUR-CONICET, Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, B8000CPB Bahía Blanca, Argentina.
María Belén
MB
Faraoni
INQUISUR-CONICET, Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, B8000CPB Bahía Blanca, Argentina. Electronic address: apmurray@uns.edu.ar.
Ana Paula
AP
Murray
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004524:Eels; D006736:Horses; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes
D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes
Alzheimer’s disease; Cholinesterase inhibitors; Lupane derivatives; Molecular modeling; Triterpenoids