In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[w-(Benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000 fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.
L. Piazzi, F. Belluti, A. Bisi, S. Gobbi, S. Rizzo, M. Bartolini, et al. (2007). CHOLINESTERASE INHIBITORS: SAR AND ENZYME INHIBITORY ACTIVITY OF 3-[omega-(BENZYLMETHYLAMINO)ALKOXY]XANTHEN-9-ONES. BIOORGANIC & MEDICINAL CHEMISTRY, 15, 575-585 [10.1016/j.bmc.2006.09.026].
CHOLINESTERASE INHIBITORS: SAR AND ENZYME INHIBITORY ACTIVITY OF 3-[omega-(BENZYLMETHYLAMINO)ALKOXY]XANTHEN-9-ONES
PIAZZI, LORNA;BELLUTI, FEDERICA;BISI, ALESSANDRA;GOBBI, SILVIA;RIZZO, STEFANO;BARTOLINI, MANUELA;ANDRISANO, VINCENZA;RECANATINI, MAURIZIO;RAMPA, ANGELA
2007
Abstract
In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[w-(Benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000 fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
