TY - JOUR
T1 - Inhibition of acetylcholinesterase by two arylderivatives
T2 - 3a-Acetoxy-5H-pyrrolo(1,2-a) (3,1)benzoxazin-1,5-(3aH)-dione and cis-N-p-Acetoxy-phenylisomaleimide
AU - Correa-Basurto, José
AU - Espinosa-Raya, Judith
AU - González-May, Mario
AU - Espinoza-Fonseca, L. Michel
AU - Vázquez-Alcántara, Iván
AU - Trujillo-Ferrara, José
N1 - Funding Information:
We are grateful to CONACyT and COFAA and SIP-IPN for scholarships and financial support to the Authors. L.M.E.F’s research is supported by grants from the Department of Biochemistry, Structural Biology and Biophysics, and the Minnesota Supercomputing Institute, University of Minnesota, USA.
PY - 2006/4
Y1 - 2006/4
N2 - 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 μM for 3 and 3.6 ± 1.8 μM for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made π-π interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed ΔG 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.
AB - 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 μM for 3 and 3.6 ± 1.8 μM for 4) in in vitro studies. Moreover, they behaved as irreversible inhibitors and made π-π interaction with W84 and hydrogen bonded with S200 and Y337 according to experimental data and docking calculations. The docking calculations showed ΔG 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.
KW - AChE
KW - Acetylcholinesterase
KW - Alzheimer
KW - Anilines
KW - Arylderivatives
KW - Docking
KW - Inhibitors
UR - http://www.scopus.com/inward/record.url?scp=33746146784&partnerID=8YFLogxK
U2 - 10.1080/14756360500480251
DO - 10.1080/14756360500480251
M3 - Artículo
SN - 1475-6366
VL - 21
SP - 133
EP - 138
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 2
ER -