นโยบายงานวิจัย /จรรยาบรรณนักวิจัย /ระดับคุณภาพบทความวิจัยตีพิมพ์ /ระดับคุณภาพผลงานวิชาการ /แหล่งทุน /ดาวน์โหลด /ฐานข้อมูลวิจัย /วิเคราะห์-สังเคราะห์งานวิจัย /ลิขสิทธิ์ /ข่าว


Synthesis, biological evaluation and molecular modeling study of novel tacrineecarbazole hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease

Author

-

Supatra Thiratmatrakul a, Chavi Yenjai b, Pornthip Waiwut c, Opa Vajragupta d,

Prasert Reubroycharoen e, Michihisa Tohda f,g, Chantana Boonyarat a,*


Journal

- European Journal of Medicinal Chemistry

Volume

- 75

Year

- 2014

Publication type

- Research article (Inter)

Page list

- 21-30

Abstract

   

New tacrineecarbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for
their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high
inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.03 mM and
exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular
modeling studies revealed that these tacrineecarbazole hybrids interacted simultaneously with the
catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The derivatives containing
methoxy group showed potent ABTS radical scavenging activity. Considering their neuroprotection, our
results indicate that these derivatives can reduce neuronal death induced by oxidative stress and bamyloid
(Ab). Moreover, S1, the highest potency for both radical scavenging and AChE inhibitory activity,
exhibited an ability to improve both short-term and long-term memory deficit in mice induced by
scopolamine. Overall, tacrineecarbazole derivatives can be considered as a candidate with potential
impact for further pharmacological development in Alzheimer’s therapy.

Keywords

   

Alzheimers disease

Carbazole

Tacrine

Cholinesterase

Antioxidant

Molecular modeling