RESUMO
Two arylderivatives, 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione 3 and cis-N-p-Acetoxy-phenylisomaleimide 4, were synthesized from anthranilic acid and para-aminophenol, respectively. The inhibitory effects of these compounds on acetylcholinesterase (AChE) activity were evaluated in vitro as well as by docking simulations. Both compounds showed inhibition of AChE activity (Ki = 4.72 +/- 2.3 microM for 3 and 3.6 +/- 1.8 microM for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made pi-pi interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed deltaG bind (kcal/mol) of - 9.22 for 3 and - 8.58 for 4. These two compounds that can be use as leads for a new family of anti-Alzheimer disease drugs.
Assuntos
Acetilcolinesterase/metabolismo , Benzoxazinas/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Maleimidas/química , Maleimidas/farmacologia , Pirróis/farmacologia , Acetilcolinesterase/química , Benzoxazinas/síntese química , Benzoxazinas/química , Sítios de Ligação , Inibidores da Colinesterase/síntese química , Cinética , Maleimidas/síntese química , Modelos Moleculares , Pirróis/síntese química , Pirróis/química , TermodinâmicaRESUMO
p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase inhibitors (AChEIs). Finding a correlation between AChE activity with the partition coefficient (log P) and the highest occupied molecular orbital (HOMO) energy of the compounds.
