Chalcone Derivatives with a High Potential As Multifunctional Antioxidant Neuroprotectors

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Nov 7

PMID 36340167

Authors

Adriana Perez-Gonzalez

Romina Castaneda-Arriaga

Eduardo Gabriel Guzman-Lopez

Luis Felipe Hernandez-Ayala

Annia Galano

Affiliations

Soon will be listed here.

Abstract

A systematic, rational search for chalcone derivatives with multifunctional behavior has been carried out, with the support of a computer-assisted protocol (CADMA-Chem). A total of 568 derivatives were constructed by incorporating functional groups into the chalcone structure. Selection scores were calculated from ADME properties, toxicity, and manufacturability descriptors. They were used to select a subset of molecules (23) with the best drug-like behavior. Reactivity indices were calculated for this subset. They were chosen to account for electron and hydrogen atom donating capabilities, which are key processes for antioxidant activity. The indexes showed that four chalcone derivatives (dCHA-279, dCHA-568, dCHA-553, and dCHA-283) are better electron and H donors than the parent molecule and some reference antioxidants (Trolox, ascorbic acid, and α-tocopherol). In addition, based on molecular docking, they are predicted to act as catechol--methyltransferase (COMT), acetylcholinesterase (AChE), and monoamine oxidase B (MAO-B) inhibitors. Therefore, these four molecules are proposed as promising candidates to act as multifunctional antioxidants with neuroprotective effects.

Citing Articles

Synthesis and Evaluation of Antibacterial and Antifungal Activities and of Novel Morpholinoalkoxychalcones.

Phan H, Mai T, Don T, Do D, Thai K, Tran T Med Chem. 2025; 21(1):61-68.

PMID: 39916436 DOI: 10.2174/0115734064316022240801093905.

Computer-aided design of caffeic acid derivatives: free radical scavenging activity and reaction force.

Morales-Garcia B, Perez-Gonzalez A, Alvarez-Idaboy J, Galano A J Mol Model. 2024; 31(1):30.

PMID: 39729167 PMC: 11680653. DOI: 10.1007/s00894-024-06226-2.

Medicinally Privileged Natural Chalcones: Abundance, Mechanisms of Action, and Clinical Trials.

Villa S, Heckman J, Bandyopadhyay D Int J Mol Sci. 2024; 25(17).

PMID: 39273572 PMC: 11395320. DOI: 10.3390/ijms25179623.

Halogenated Analogs to Natural A-Type Proanthocyanidins: Evaluation of Their Antioxidant and Antimicrobial Properties and Possible Application in Food Industries.

Cobo A, Alejo-Armijo A, Cruz D, Altarejos J, Salido S, Ortega-Morente E Molecules. 2024; 29(15).

PMID: 39125027 PMC: 11314616. DOI: 10.3390/molecules29153622.

Synthesis, pharmacological evaluation, and study of new 3-furan-1-thiophene-based chalcones as antibacterial and anticancer agents.

Abdula A, Mohsen G, Jasim B, Jabir M, Rushdi A, Baqi Y Heliyon. 2024; 10(11):e32257.

PMID: 38947436 PMC: 11214363. DOI: 10.1016/j.heliyon.2024.e32257.

References

Stephens N, Parsons A, Schofield P, Kelly F, Cheeseman K, Mitchinson M . Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996; 347(9004):781-6. DOI: 10.1016/s0140-6736(96)90866-1. View

Street D, Comstock G, Salkeld R, Schuep W, Klag M . Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction?. Circulation. 1994; 90(3):1154-61. DOI: 10.1161/01.cir.90.3.1154. View

Jin C, Liang Y, He H, Fu L . Synthesis and antitumor activity of novel chalcone derivatives. Biomed Pharmacother. 2013; 67(3):215-7. DOI: 10.1016/j.biopha.2010.12.010. View

Szoko E, Tabi T, Riederer P, Vecsei L, Magyar K . Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson's disease. J Neural Transm (Vienna). 2018; 125(11):1735-1749. DOI: 10.1007/s00702-018-1853-9. View

Chidan Kumar C, Loh W, Ooi C, Quah C, Fun H . Structural correlation of some heterocyclic chalcone analogues and evaluation of their antioxidant potential. Molecules. 2013; 18(10):11996-2011. PMC: 6270477. DOI: 10.3390/molecules181011996. View

Pavan S, Prabhu A, Gorthi S, Das B, Mutreja A, Shetty V . Exploring the multifactorial aspects of Gut Microbiome in Parkinson's Disease. Folia Microbiol (Praha). 2022; 67(5):693-706. PMC: 9526693. DOI: 10.1007/s12223-022-00977-2. View

Li J, Li D, Xu Y, Guo Z, Liu X, Yang H . Design, synthesis, biological evaluation, and molecular docking of chalcone derivatives as anti-inflammatory agents. Bioorg Med Chem Lett. 2016; 27(3):602-606. DOI: 10.1016/j.bmcl.2016.12.008. View

Uddin M, Al Mamun A, Rahman M, Behl T, Perveen A, Hafeez A . Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease. Curr Top Med Chem. 2020; 20(26):2380-2390. DOI: 10.2174/1568026620666200601161703. View

Zhao Y, Schultz N, Truhlar D . Design of Density Functionals by Combining the Method of Constraint Satisfaction with Parametrization for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions. J Chem Theory Comput. 2015; 2(2):364-82. DOI: 10.1021/ct0502763. View

10.

El-Sayed Y, Gaber M . Studies on chalcone derivatives: complex formation, thermal behavior, stability constant and antioxidant activity. Spectrochim Acta A Mol Biomol Spectrosc. 2014; 137:423-31. DOI: 10.1016/j.saa.2014.08.061. View

11.

Alvarez-Diduk R, Ramirez-Silva M, Galano A, Merkoci A . Deprotonation mechanism and acidity constants in aqueous solution of flavonols: a combined experimental and theoretical study. J Phys Chem B. 2013; 117(41):12347-59. DOI: 10.1021/jp4049617. View

12.

Iturria-Medina Y, Hachinski V, Evans A . The vascular facet of late-onset Alzheimer's disease: an essential factor in a complex multifactorial disorder. Curr Opin Neurol. 2017; 30(6):623-629. DOI: 10.1097/WCO.0000000000000497. View

13.

Pouget C, Lauthier F, Simon A, Fagnere C, Basly J, Delage C . Flavonoids: structural requirements for antiproliferative activity on breast cancer cells. Bioorg Med Chem Lett. 2001; 11(24):3095-7. DOI: 10.1016/s0960-894x(01)00617-5. View

14.

Zhu H, Tropsha A, Fourches D, Varnek A, Papa E, Gramatica P . Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis. J Chem Inf Model. 2008; 48(4):766-84. DOI: 10.1021/ci700443v. View

15.

Salonen J, Nyyssonen K, Korpela H, Tuomilehto J, Seppanen R, Salonen R . High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation. 1992; 86(3):803-11. DOI: 10.1161/01.cir.86.3.803. View

16.

Leon-Carmona J, Martinez A, Galano A . New free radicals to measure antiradical capacity: a theoretical study. J Phys Chem B. 2014; 118(34):10092-100. DOI: 10.1021/jp505586k. View

17.

Stepanic V, Matijasic M, Horvat T, Verbanac D, Kucerova-Chlupacova M, Saso L . Antioxidant Activities of Alkyl Substituted Pyrazine Derivatives of Chalcones-In Vitro and In Silico Study. Antioxidants (Basel). 2019; 8(4). PMC: 6523444. DOI: 10.3390/antiox8040090. View

18.

Schneider G, Fechner U . Computer-based de novo design of drug-like molecules. Nat Rev Drug Discov. 2005; 4(8):649-63. DOI: 10.1038/nrd1799. View

19.

Butterfield D, Hensley K, Harris M, Mattson M, Carney J . beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease. Biochem Biophys Res Commun. 1994; 200(2):710-5. DOI: 10.1006/bbrc.1994.1508. View

20.

Fay D, Fluet A, Johnson C, Link C . In vivo aggregation of beta-amyloid peptide variants. J Neurochem. 1998; 71(4):1616-25. DOI: 10.1046/j.1471-4159.1998.71041616.x. View