CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants.
Eduardo Gabriel Guzman-LopezMiguel ReinaAdriana Perez-GonzalezMisaela Francisco-MarquezLuis Felipe Hernández-AyalaRomina Castañeda-ArriagaAnnia GalanoPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- human health
- randomized controlled trial
- risk assessment
- oxidative stress
- healthcare
- drug delivery
- climate change
- emergency department
- small molecule
- cancer therapy
- signaling pathway
- type diabetes
- mental health
- high throughput
- brain injury
- adipose tissue
- metabolic syndrome
- circulating tumor
- insulin resistance
- single molecule
- health information
- binding protein
- electronic health record
- cerebral ischemia
- mild cognitive impairment