Diet is an essential factor affecting the development of and risk for diabetes mellitus. In search of preventative and therapeutic strategies, it is to be considering the potential role of certain foods and their bioactive compounds to prevent the pathogenesis associated with metabolic diseases. Human consumption of anthocyanins is among the highest of all flavonoids. Epidemiological studies have suggested that the consumption of anthocyanins lowers the risk of diabetes and diabetic complications. Anthocyanins are important natural bioactive pigments responsible for red to blue colour of fruits, leaves, seeds, stems and flowers, which are present in a variety of plant species particularly in berries and cherries. A large number of bioactive anthocyanins, such as cyanidin, malvidin, delphinidin, pelargonidin, peonidin, petunidin and their metabolites have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion and sensitivity, on the enzymes involved in glucose metabolism, gene expressions, inflammatory mediators, glucose transporters in progression of diabetes and associated complications, such as diabetic retinopathy, nephropathy, neuropathy and diabetic vascular diseases. The versatility of the anthocyanins provides a promising approach for diabetes management than synthetic drugs. Here we summarize effect of several anthocyanins on many in vitro, in vivo and clinical studies and also reveals the mechanisms which could prevent or reverse the underlying mechanisms of diabetic pathologies including promotion of antioxidant, anti-hyperlipidemic, anti-inflammatory and anti-apoptotic activities.

Parasitic diseases remain as unresolved health issues worldwide. While for some parasites the treatments involve drug combinations with serious side effects, for others, chemical therapies are inefficient due to the emergence of drug resistance. This urges the search for novel antiparasitic agents able to act through multiple mechanisms of action. Here, we report the first multi-target model based on quantitative structure-activity relationships and a multilayer perceptron neural network (mt-QSAR-MLP) to virtually design and predict versatile inhibitors of proteins involved in the survival and/or infectivity of different pathogenic parasites. The mt-QSAR-MLP model exhibited high accuracy (>80%) in both training and test sets for the classification/prediction of protein inhibitors. Several fragments were directly extracted from the physicochemical and structural interpretations of the molecular descriptors in the mt-QSAR-MLP model. Such interpretations enabled the generation of four molecules that were predicted as multi-target inhibitors against at least three of the five parasitic proteins reported here with two of the molecules being predicted to inhibit all the proteins. Docking calculations converged with the mt-QSAR-MLP model regarding the multi-target profile of the designed molecules. The designed molecules exhibited drug-like properties, complying with Lipinski’s rule of five, as well as Ghose’s filter and Veber’s guidelines.

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Benzodiazepines (BZ or BZD) are a class of gabaminergic psychoactive chemicals used in hypnotics, sedation, in the treatment of anxiety, and in other CNS disorders. These drugs include alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), and others. There are two distinct types of pharmacological binding sites for benzodiazepines in the brain (BZ1 and BZ2), these sites are on GABA-A receptors, and are classified as short, intermediate, or long-acting. From the thienobenzodiazepine class (TBZ), Olanzapine (2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) (Zyprexa) was used as an example to demonstrate the antagonism of this class of compounds for multiples receptors including: dopamine D1-D5, α-adrenoreceptor, histamine H1, muscarinic M1-M5 and 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3 and 5-HT6 receptors. Olanzapine is an atypical antipsychotic agent, structurally related to clozapine, and extensively used for the treatment of schizophrenia, bipolar disorder-associated mania, and the behavioral symptoms of Alzheimer's disease. The functional blockade of these multiple receptors contributes to the wide range of its pharmacologic and therapeutic activities, having relatively few side effects when compared to other antipsychotics agents. Thienobenzodiazepines (such as Olanzapine) are characterized as multi- receptor- targeted- acting- agents. This mini-review discusses these 2 drug classes that act on the central nervous system, the main active compounds used, and the various receptors with which they interact. In addition, we propose 12 olanzapine analogues, and generated Random Forest models, from a data set obtained from the ChEMBL database, to classify the structures as active or inactive against 5 dopamine receptors (D1, D2, D3, D4, D5 and D6), and dopamine transporter.

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Tissue damage due to oxidative stress is directly linked to development of many, if not all, human morbidity factors and chronic diseases. In this context, the search for dietary natural occurring molecules with antioxidant activity, such as flavonoids, has become essential. In this study, we investigated a set of 41 flavonoids (23 flavones and 18 flavonols) analyzing their structures and biological antioxidant activity. The experimental data were submitted to a QSAR (quantitative structure-activity relationships) study. NMR 13 C data were used to perform a Kohonen self-organizing map study, analyzing the weight that each carbon has in the activity. Additionally, we performed MLR (multilinear regression) using GA (genetic algorithms) and molecular descriptors to analyze the role that specific carbons and substitutions play in the activity.Uniterms: Flavonoids/antioxidant activity. 13C NMR. Kohonen self-organizing map.Danos aos tecidos devido ao estresse oxidativo estão diretamente ligados ao desenvolvimento de muitos, senão todos, os fatores de sedentarismo e de doenças crônicas. Neste contexto, a busca de moléculas naturais, que participam da nossa dieta e que possuam atividade antioxidante, flavonóides, torna-se de grande interesse. Neste estudo, nós investigamos um conjunto de 41 flavonóides (23 flavonas e 18 flavonóis), relacionando suas estruturas e atividade antioxidante. Os dados experimentais foram submetidos à análise de QSAR (relações quantitativas estrutura-atividade). Dados de RMN 13 C foram utilizados para realizar um estudo do mapa auto-organizável de Kohonen, analisando o peso que cada carbono tem na atividade. Além disso, realizamos uma MLR (regressão múltipla) usando GA (algoritmos genéticos) e descritores moleculares para avaliar a influência de carbonos e substituições na atividade. Unitermos: RMN 13C. Flavonóides/atividade antioxidante. Mapa auto-organizável de Kohonen.

Background: Metabolic disorders are a major cause of illness and death worldwide. Metabolism is the process by which the body makes energy from proteins, carbohydrates, and fats; chemically breaking these down in the digestive system towards sugars and acids which constitute the human body's fuel for immediate use, or to store in body tissues, such as the liver, muscles, and body fat. Objective: The efficiency of treatments for multifactor diseases has not been proved. It is accepted that to manage multifactor diseases, simultaneous modulation of multiple targets is required leading to the development of new strategies for discovery and development of drugs against metabolic disorders. Methods: In silico studies are increasingly being applied by researchers due to reductions in time and costs for new prototype synthesis; obtaining substances that present better therapeutic profiles. Discussion: In the present work, in addition to discussing multi-target drug discovery and the contributions of in silico studies to rational bioactive planning against metabolic disorders such as diabetes and obesity, we review various in silico study contributions to the fight against human metabolic pathologies. Conclusion: In this review, we have presented various studies involved in the treatment of metabolic disorders; attempting to obtain hybrid molecules with pharmacological activity against various targets and expanding biological activity by using different mechanisms of action to treat a single pathology.

Chalcones are direct precursors in the biosynthesis of flavonoids. They have an α,β-unsaturated carbonyl system which gives them broad biological properties. Among the biological properties exerted by chalcones, their ability to suppress tumors stands out, in addition to their low toxicity. In this perspective, the present work explores the role of natural and synthetic chalcones and their anticancer activity in vitro reported in the last four years from 2019 to 2023. Moreover, we carried out a partial least square (PLS) analysis of the biologic data reported for colon adenocarcinoma lineage HCT-116. Information was obtained from the Web of Science database. Our in silico analysis identified that the presence of polar radicals such as hydroxyl and methoxyl contributed to the anticancer activity of chalcones derivatives. We hope that the data presented in this work will help researchers to develop effective drugs to inhibit colon adenocarcinoma in future works.