TY - JOUR
T1 - CADMA-Chem
T2 - A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants
AU - Guzman-Lopez, Eduardo Gabriel
AU - Reina, Miguel
AU - Perez-Gonzalez, Adriana
AU - Francisco-Marquez, Misaela
AU - Hernandez-Ayala, Luis Felipe
AU - Castañeda-Arriaga, Romina
AU - Galano, Annia
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson’s and Alzheimer’s diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor–ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.
AB - A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson’s and Alzheimer’s diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor–ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.
KW - ADME
KW - QSAR
KW - kinetics
KW - melatonin
KW - molecular design
KW - reactivity indexes
KW - selection score
KW - toxicity
UR - http://www.scopus.com/inward/record.url?scp=85141584730&partnerID=8YFLogxK
U2 - 10.3390/ijms232113246
DO - 10.3390/ijms232113246
M3 - Artículo
C2 - 36362034
AN - SCOPUS:85141584730
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 13246
ER -