Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease

Burcu Kılıç

Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease

Abstract

Alzheimer’s Disease (AD) is one of the most devastating chronic health problems of the last few decades. Unfortunately, current treatment and care options for AD are insufficient, making it a prominent topic for drug discovery studies. Currently, AD drug development studies have focused on the strategy of multitarget directed ligands (MTDLs). Following this strategy, we designed new ChE inhibitors with additional antioxidant and metal chelator effects. In this research, we designed and synthesized novel eight N’-(4-oxo-4H-chromen-3-yl)methylene propanehydrazide derivatives. We then evaluated the inhibition potency of all final compounds for cholinesterase enzymes. Among them, (6f) (IC50 AChE=16.91 µM) was found to be the most potent acetylcholinesterase inhibitor. Additionally, (6d) (IC50’s AChE=26.91 µM and BChE=47.94 µM) exhibited dual cholinesterase inhibitor activity. Moreover, we investigated all title compounds for their antioxidant (DPPH, ORAC) and metal chelator activities. According to the ORAC-FL results, all the compounds exhibited good antioxidant activity ranging from 4.082 to 16.715 Trolox equivalents. We also observed chelator effects of all compounds for Cu(II), Fe(II), and Zn(II) ions at varying rates. Furthermore, we assessed the in-silico physicochemical parameters of the compounds to evaluate their drug-likeness or druggability.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Clinical Research

Authors

Burcu Kılıç ^*
0000-0001-8737-829X
Türkiye

Publication Date

June 28, 2025

Submission Date

July 21, 2023

Acceptance Date

October 26, 2023

Published in Issue

Year 2024 Volume: 28 Number: 5

IZ

https://izlik.org/JA45PL33TK

Cite

RIS / Bibtex

APA

Kılıç, B. (2025). Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease. Journal of Research in Pharmacy, 28(5), 1344-1356. https://izlik.org/JA45PL33TK

AMA

1.Kılıç B. Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease. J. Res. Pharm. 2025;28(5):1344-1356. https://izlik.org/JA45PL33TK

Chicago

Kılıç, Burcu. 2025. “Design, Synthesis, and Biological Evaluation of Novel N’-(4-Oxo-4H-Chromen-3-Yl) Methylene Propanehydrazides for Alzheimer’s Disease”. Journal of Research in Pharmacy 28 (5): 1344-56. https://izlik.org/JA45PL33TK.

EndNote

Kılıç B (July 1, 2025) Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease. Journal of Research in Pharmacy 28 5 1344–1356.

IEEE

[1]B. Kılıç, “Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease”, J. Res. Pharm., vol. 28, no. 5, pp. 1344–1356, July 2025, [Online]. Available: https://izlik.org/JA45PL33TK

ISNAD

Kılıç, Burcu. “Design, Synthesis, and Biological Evaluation of Novel N’-(4-Oxo-4H-Chromen-3-Yl) Methylene Propanehydrazides for Alzheimer’s Disease”. Journal of Research in Pharmacy 28/5 (July 1, 2025): 1344-1356. https://izlik.org/JA45PL33TK.

JAMA

1.Kılıç B. Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease. J. Res. Pharm. 2025;28:1344–1356.

MLA

Kılıç, Burcu. “Design, Synthesis, and Biological Evaluation of Novel N’-(4-Oxo-4H-Chromen-3-Yl) Methylene Propanehydrazides for Alzheimer’s Disease”. Journal of Research in Pharmacy, vol. 28, no. 5, July 2025, pp. 1344-56, https://izlik.org/JA45PL33TK.

Vancouver

1.Burcu Kılıç. Design, synthesis, and biological evaluation of novel N’-(4-oxo-4H-chromen-3-yl) methylene propanehydrazides for Alzheimer’s disease. J. Res. Pharm. [Internet]. 2025 Jul. 1;28(5):1344-56. Available from: https://izlik.org/JA45PL33TK