Quinoline has been proposed as a privileged molecular framework in medicinal chemistry. Although by itself it has very few applications, its derivatives have diverse biological activities. In this work, 8536 quinoline derivatives, strategically designed using the CADMA-Chem protocol, are presented. This large chemical space was sampled, analyzed and reduced using selection and elimination scores that combine their properties of bioavailability, toxicity and manufacturability. After applying several filters, 25 derivatives were selected to investigate their acid–base, antioxidant and neuroprotective properties. The antioxidant activity was predicted based on the ionization potential and bond dissociation energies, parameters directly related to the transfer of hydrogen atoms and of a single electron, respectively. These two mechanisms are typically involved in the radical scavenging processes. The antioxidant efficiency was compared with reference compounds, and the most promising antioxidants were found to be more efficient than Trolox but less efficient than ascorbate. In addition, based on molecular docking simulations, some derivatives are expected to act as inhibitors of catechol-O methyltransferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase type B (MAO-B) enzymes. Some structural insights about the compounds were found to enhance or decrease the neuroprotection activity. Based on the results, four quinoline derivatives are proposed as candidates to act as multifunctional antioxidants against Alzheimer’s (AD) and Parkinson’s (PD) diseases.

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.

Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated. To that purpose, selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes directly related to the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and α-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directly related to the etiologies of Parkinson’s and Alzheimer’s diseases. These enzymes are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.

Although melatonin is an astonishing molecule, it is possible that chemistry will help in the discovery of new compounds derived from it that may exceed our expectations regarding antioxidant protection and perhaps even neuroprotection. This review briefly summarizes the significant amount of data gathered to date regarding the multiple health benefits of melatonin and related compounds. This review also highlights some of the most recent directions in the discovery of multifunctional pharmaceuticals intended to act as one-molecule multiple-target drugs with potential use in multifactorial diseases, including neurodegenerative disorders. Herein, we discuss the beneficial activities of melatonin derivatives reported to date, in addition to computational strategies to rationally design new derivatives by functionalization of the melatonin molecular framework. It is hoped that this review will promote more investigations on the subject from both experimental and theoretical perspectives.

In the Digital Era, the development of new educational instruments is crucial for supporting students in their academic journey. While there is a significant correlation between homework and learning, the effectiveness of assignments is often constrained by the large number of students and the extensive grading required by teachers. In this context, open educational resources (OER), particularly those built on the free and open-source Moodle platform, have shown increased learning among students, becoming valuable instruments for educators. Automated chemistry assignments are challenging, in contrast to physics or mathematics. This is due to the necessity of accounting for the vast yet finite universe of existing molecules, compounds, and reactions along with the inherent constraints imposed within the field. In this article we present PLATA (Programa en Línea de Apoyo a las Tareas Académicas), a Moodle based OER for automated chemistry homework implemented at Facultad de Química at UNAM. PLATA is an online platform with more than 132 million open answer exercises (not multiple choice) automatically graded with specific feedback for each exercise attempt. The design and characteristics of the program, some examples showing its versatility, and the outstanding students’ outcomes of the OER are presented. PLATA has been used by more than 15,500 students over the past 4 years. The results displayed correspond to the 2022 academic year, with more than 3,200 students, from which 500 undergraduates answered an exit survey, and we monitored the outcomes of 400 students. As a result, we can state that PLATA is a versatile, useful, and robust program for chemistry assignments with a positive impact on students’ learning.

Ferulic acid has numerous beneficial effects for human health, which are frequently attributed to its antioxidant behavior. In this report many of them are reviewed and 185 new ferulic acid derivatives are computationally designed, using the CADMA-Chem protocol. For the later, the chemical space was sampled and evaluated. To that purpose selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes, directed related with the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and alpha-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directed related with the etiologies of Parkinson’s and Alzheimer’s diseases. They are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.