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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease

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Author(s):
Fernandes, Thais B. [1] ; Cunha, Micael R. [1] ; Sakata, Renata P. [2] ; Candido, Thalita M. [1] ; Baby, Andre R. [1] ; Tavares, Mauricio T. [1] ; Barbosa, Euzebio G. [3] ; Almeida, Wanda P. [2] ; Parise-Filho, Roberto [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, Av Prof Lineu Prestes Ave 580, Cidade Univ, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Estadual Campinas, Dept Pharm, Fac Pharmaceut Sci, Campinas, SP - Brazil
[3] Univ Fed Rio Grande do Norte, Dept Pharm, Hlth Sci Ctr, Natal, RN - Brazil
Total Affiliations: 3
Document type: Journal article
Source: ARCHIV DER PHARMAZIE; v. 350, n. 11 NOV 2017.
Web of Science Citations: 4
Abstract

Alzheimer's disease (AD) is the most common type of dementia and related to the degeneration of hippocampal cholinergic neurons, which dramatically affects cognitive ability. Acetylcholinesterase (AChE) inhibitors are employed as drugs for AD therapy. Three series of sulfonylhydrazone compounds were designed, and their ability to inhibit AChE was evaluated. Fifteen compounds were synthesized and twelve of them had IC50 values of 0.64-51.09M. The preliminary structure-activity relationships indicated that the methylcatechol moiety and arylsulfonyl substituents generated better compounds than both the benzodioxole and alkylsulfonyl chains. Molecular dynamics studies of compound 6d showed that the interaction with the peripheral binding site of AChE was similar to donepezil, which may explain its low IC50 (0.64M). Furthermore, the drug-likeness of 6d suggests that the compound may have appropriate oral absorption and brain penetration. Compound 6d also presented antiradical activity and was not cytotoxic to LL24 cells, suggesting that this compound might be considered safe. Our findings indicate that arylsulfonylhydrazones may be a promising scaffold for the design of new drug candidates for the treatment of AD. (AU)

FAPESP's process: 13/19311-6 - Design, synthesis and antitumor activity of aryl-sulfonylhydrazone compounds
Grantee:Thais Batista Fernandes
Support Opportunities: Scholarships in Brazil - Master