دورية أكاديمية
Design of Multitarget Natural Products Analogs with Potential Anti-Alzheimer's Activity.
| العنوان: | Design of Multitarget Natural Products Analogs with Potential Anti-Alzheimer's Activity. |
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| المؤلفون: | de Souza FN; Laboratory of Medicinal and Pharmaceutical Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil., de Lima HB; Laboratory of Medicinal and Pharmaceutical Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil., de Souza LR; Laboratory of Medicinal and Pharmaceutical Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil., Oliveira GS; Laboratory of Medicinal and Pharmaceutical Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil., de Paula da Silva CHT; Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Pereira ACM; Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., da Silva Hage-Melim LI; Laboratory of Medicinal and Pharmaceutical Chemistry (PharMedChem), Federal University of Amapá, Macapá, Amapá, Brazil. |
| المصدر: | Current computer-aided drug design [Curr Comput Aided Drug Des] 2022; Vol. 18 (2), pp. 120-149. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101265750 Publication Model: Print Cited Medium: Internet ISSN: 1875-6697 (Electronic) Linking ISSN: 15734099 NLM ISO Abbreviation: Curr Comput Aided Drug Des Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, c2005- |
| مواضيع طبية MeSH: | Alzheimer Disease*/drug therapy , Biological Products*/chemistry , Biological Products*/pharmacology, Acetylcholinesterase ; Aged ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/pharmacology ; Humans ; Molecular Docking Simulation |
| مستخلص: | Background: Alzheimer's disease (AD) is a neurodegenerative condition and the most common type of dementia among the elderly. The enzymes acetylcholinesterase (AChE) and nitric oxide synthase (NOS) have a pivotal role in the pathophysiology of this disease. Objective: This study aimed to select medicinal plant-derived molecules with reported inhibition of AChE and design optimized molecules that could inhibit not only AChE, but also NOS, potentially increasing its efficacy against AD. Methods: 24 compounds were selected from the literature based on their known AChE inhibitory activity. Then, we performed molecular orbital calculations, maps of electrostatic potential, molecular docking study, identification of the pharmacophoric pattern, evaluation of pharmacokinetic and toxicological properties of these molecules. Next, ten analogs were generated for each molecule to optimize their effect where the best molecules of natural products had failed. Results: The most relevant correlation was between HOMO and GAP in the correlation matrix of the molecules' descriptors. The pharmacophoric group's derivation found the following pharmacophoric features: two hydrogen bond acceptors and one aromatic ring. The studied molecules interacted with the active site of AChE through hydrophobic and hydrogen bonds and with NOS through hydrogen interactions only but in a meaningful manner. In the pharmacokinetic and toxicological prediction, the compounds showed satisfactory results. Conclusion: The design of natural products analogs demonstrated good affinities with the pharmacological targets AChE and NOS, with satisfactory pharmacokinetics and toxicology profiles. Thus, the results could identify promising molecules for treating Alzheimer's disease. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| معلومات مُعتمدة: | 427831/2016-4, 465.249/2014-0 National Council for Scientific and Technological Development (CNPq); E-26/010.000090/2018 FAPERJ, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro |
| فهرسة مساهمة: | Keywords: Alzheimer's disease; NOS; acetylcholinesterase; correlation matrix; natural products; nitric oxide synthase |
| المشرفين على المادة: | 0 (Biological Products) 0 (Cholinesterase Inhibitors) EC 3.1.1.7 (Acetylcholinesterase) |
| تواريخ الأحداث: | Date Created: 20220329 Date Completed: 20220728 Latest Revision: 20220802 |
| رمز التحديث: | 20231215 |
| DOI: | 10.2174/1573409918666220328141605 |
| PMID: | 35346014 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-6697 |
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| DOI: | 10.2174/1573409918666220328141605 |