Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase

Article abstract of DOI:10.1016/j.bioorg.2019.102960

In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q)were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the Aβ aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 × 10⁴, 2.22 × 10⁴, 1.18 × 10⁴, 9.8 × 10³ and 3.2 × 10⁴ M^?1 and free energy change as ?5.83, ?5.91, ?5.51, ?5.41 and ?6.12 kcal M^?1 at 25 °C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i.

Full text of DOI:10.1016/j.bioorg.2019.102960

Accepted Manuscript
Synthesis and biological evaluation of flavone-8-acrylamide derivatives as po-
tential multi-target-directed anti Alzheimer agents and investigation of binding
mechanism with acetylcholinesterase
Jeelan Basha Shaik, Daniel Pushparaju Yeggoni, Yelamanda Rao Kandrakonda,
Mohan Penumala, Raveendra Babu Zinka, Kasi Viswanath Kotapati, Mark
Manidhar Darla, Dinakara Rao Ampasala, Rajagopal Subramanyam, Amooru
Gangaiah Damu
PII:
S0045-2068(19)30044-6
https://doi.org/10.1016/j.bioorg.2019.102960
102960
DOI:
Article Number:
Reference:
YBIOO 102960
Bioorganic Chemistry
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Revised Date:
Accepted Date:
10 January 2019
18 April 2019
28 April 2019
Please cite this article as: J. Basha Shaik, D. Pushparaju Yeggoni, Y. Rao Kandrakonda, M. Penumala, R. Babu
Zinka, K. Viswanath Kotapati, M. Manidhar Darla, D. Rao Ampasala, R. Subramanyam, A. Gangaiah Damu,
Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti
Alzheimer agents and investigation of binding mechanism with acetylcholinesterase, Bioorganic Chemistry (2019),
doi: https://doi.org/10.1016/j.bioorg.2019.102960
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