Current Pharmaceutical Design - Volume 26, Issue 33, 2020

Research regarding polyphenols has gained prominence over the years because of their potential as pharmacological nutrients. Most polyphenols are flavanols, commonly known as catechins, which are present in high amounts in green tea. Catechins are promising candidates in the field of biomedicine. The health benefits of catechins, notably their antioxidant effects, are related to their chemical structure and the total number of hydroxyl groups. In addition, catechins possess strong activities against several pathogens, including bacteria, viruses, parasites, and fungi. One major limitation of these compounds is low bioavailability. Catechins are poorly absorbed by intestinal barriers. Some protective mechanisms may be required to maintain or even increase the stability and bioavailability of these molecules within living organisms. Moreover, novel delivery systems, such as scaffolds, fibers, sponges, and capsules, have been proposed. This review focuses on the unique structures and bioactive properties of catechins and their role in inflammatory responses as well as provides a perspective on their use in future human health applications.

Medicinal plants produce secondary metabolites with special biological activities, which may be used as new therapeutic alternatives. For instance, tea tree essential oil (TTO) was shown to exert antimicrobial, antifungal, anthelmintic, antiviral, anti-tumor and anti-inflammatory activities. Due to their thermal instability, active principles can be easily degraded by physicochemical processes; therefore, they must be protected to increase their time of action and improve their controlled release. The aim of this review is to discuss formulations incorporating encapsulated TTO as the active ingredient. Micro and nanoencapsulated systems proved to be more thermostable than TTO and to exert better antimicrobial, antifungal, antiparasitic and larvicidal effects. Nanoencapsulation also reduced oil toxicity. Emulsified and hybrid systems developed by various methods showed improved repellent, antibacterial, antifungal and anti-inflammatory activities, thereby proving promising for the pharmaceutical industry. Liposomal formulations produced by hydration of lipid films exhibited constant rate of terpinen-4-ol release. In addition, their incorporation into biomaterials, such as sponges, nanofibers and films, showed great potential for treating infections. Mainly due to the advantages of their incorporation into new drug delivery systems over conventional formulations, there is an interest in the development of systems containing TTO as a pharmaceutical ingredient of plant origin.

Species from the Annona (Anonaceae) genus are used in traditional medicine for the treatment of various diseases. Ethnobotanical studies provide information regarding the plant part and the preparation method being used, while scientific studies such as in vitro, in vivo, and clinical tests can provide evidence supporting ethnopharmacological reports, directing studies towards the isolation of compounds which may be active for specific pathologies. Annona muricata and Annona squamosa were the most commonly reported species from those studied, with Annona cherimola and Annona classiflora also standing out. Acetogenins were the most commonly isolated metabolite class due to their cytotoxic properties, with flavonoids, alkaloids, steroids, and peptides also being reported. Many species from the Annona genus have proven biological activities, such as antitumor, antioxidant, antimicrobial and antifungal. The present review had as its objective to facilitate access to ethnobotanical, chemical and biological information in order to direct future researches.

The Aedes aegypti is responsible for the transmission of arboviruses, which compromise public health. In the search for synthetic product alternatives, essential oils (OEs) have been highlighted by many researchers as natural insecticides. This systematic review (SR) was performed according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and its objective was to evaluate studies addressing OEs with larvicidal properties against Ae. aegypti, through electronic database searches (Pubmed, Science Direct and Scielo), covering an overview of the plant sources OEs, which plant parts were used, the extraction methods, analytical techniques, major and/or secondary constituents with greater percentages, as well as the LC50s responsible for larval mortality. Following study analysis, plants distributed across 32 families, 90 genera and 175 species were identified. The Lamiaceae, Myrtaceae, Piperaceae, Asteraceae, Rutaceae, Euphorbiaceae and Lauraceae families obtained the highest number of species with toxic properties against larvae from this vector. Practically all plant parts were found to be used for OE extraction. Hydrodistillation and steam distillation were the main extraction methods identified, with GC-MS/GC-FID representing the main analytical techniques used to reveal their chemical composition, especially of terpene compounds. In this context, OEs are promising alternatives for the investigation of natural, ecologically correct and biodegradable insecticides with the potential to be used in Ae. aegypti control programs.

Neglected parasitic diseases are a group of infections currently considered as a worldwide concern. This fact can be attributed to the migration of these diseases to developed and developing countries, associated with therapeutic insufficiency resulted from the low investment in the research and development of new drugs. In order to overcome this situation, bioprospecting supports medicinal chemistry in the identification of new scaffolds with therapeutically appropriate physicochemical and pharmacokinetic properties. Among them, we highlight the nitrogenous heterocyclic compounds, as they are secondary metabolites of many natural products with potential biological activity. The objective of this work was to review studies within a 10-year timeframe (2009- 2019), focusing on the pharmacological application of nitrogen bioprospectives (pyrrole, pyridine, indole, quinoline, acridine, and their respective derivatives) against neglected parasitic infections (malaria, leishmania, trypanosomiases, and schistosomiasis), and their application as a template for semi-synthesis or total synthesis of potential antiparasitic agents. In our studies, it was observed that among the selected articles, there was a higher focus on the attempt to identify and obtain novel antimalarial compounds, in a way that an extensive amount of studies involving all heterocyclic nitrogen nuclei were found. On the other hand, the parasites with the lowest number of publications up until the present date have been trypanosomiasis, especially those caused by Trypanosoma cruzi, and schistosomiasis, where some heterocyclics have not even been cited in recent years. Thus, we conclude that despite the great biodiversity on the planet, little attention has been given to certain neglected tropical diseases, especially those that reach countries with a high poverty rate.

Neurodegenerative disorders are estimated to become the second leading cause of death worldwide by 2040. Despite the widespread use of diverse allopathic drugs, these brain-associated disorders can only be partially addressed and long term treatment is often linked with dependency and other unwanted side effects. Nature, believed to be an arsenal of remedies for any illness, presents an interesting avenue for the development of novel neuroprotective agents. Interestingly, inhibition of cholinesterases, involved in the breakdown of acetylcholine in the synaptic cleft, has been proposed to be neuroprotective. This review therefore aims to provide additional insight via docking studies of previously studied compounds that have shown potent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. Indeed, the determination of potent plant-based ligands for this purpose through in silico methods enables the elimination of lengthy and costly traditional methods of drug discovery. Herein, a literature search was conducted to identify active phytochemicals which are cholinesterase inhibitors. Following which in silico docking methods were applied to obtain docking scores. Compound structures were extracted from online ZINC database and optimized using AM1 implemented in gaussian09 software. Noteworthy ligands against AChE highlighted in this study include: 19,20-dihydroervahanine A and 19, 20-dihydrotabernamine. Regarding BChE inhibition, the best ligands were found to be 8-Clavandurylkaempferol, Na-methylepipachysamine D; ebeiedinone; and dictyophlebine. Thus, ligand optimization between such phytochemicals and cholinesterases coupled with in vitro, in vivo studies and randomized clinical trials can lead to the development of novel drugs against neurodegenerative disorders.

The encapsulation of bioactive compounds is an emerging technique for finding new medicines since it provides protection against ambient degradation factors before reaching the target site. Nanotechnology provides new methods for encapsulating bioactive compounds and for drug carrier development. Nanocarriers satisfactorily impact the absorption, distribution, metabolism, and excretion rate when compared to conventional carriers. The nanocarrier material needs to be compatible and bind to the drug and be bio-resorbable. In this context, the physicochemical characterization of encapsulated bioactive compounds is fundamental to guarantee the quality, reproducibility, and safety of the final pharmaceutical product. In this review, we present the physicochemical techniques most used today by researchers to characterize bioactive compounds in nanocarriers and the main information provided by each technique, such as morphology, size, degree of crystallinity, long-term stability, the efficacy of drug encapsulation, and the amount released as a function of time.

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.

Background: The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells. Methods: An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets. Results: The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis. Conclusion: The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.

Background: Enhancing a compound’s biological activity is the central task for lead optimization in small molecules drug discovery. However, it is laborious to perform many iterative rounds of compound synthesis and bioactivity tests. To address the issue, it is highly demanding to develop high quality in silico bioactivity prediction approaches, to prioritize such more active compound derivatives and reduce the trial-and-error process. Methods: Two kinds of bioactivity prediction models based on a large-scale structure-activity relationship (SAR) database were constructed. The first one is based on the similarity of substituents and realized by matched molecular pair analysis, including SA, SA_BR, SR, and SR_BR. The second one is based on SAR transferability and realized by matched molecular series analysis, including Single MMS pair, Full MMS series, and Multi single MMS pairs. Moreover, we also defined the application domain of models by using the distance-based threshold. Results: Among seven individual models, Multi single MMS pairs bioactivity prediction model showed the best performance (R2 = 0.828, MAE = 0.406, RMSE = 0.591), and the baseline model (SA) produced the most lower prediction accuracy (R2 = 0.798, MAE = 0.446, RMSE = 0.637). The predictive accuracy could further be improved by consensus modeling (R2 = 0.842, MAE = 0.397 and RMSE = 0.563). Conclusion: An accurate prediction model for bioactivity was built with a consensus method, which was superior to all individual models. Our model should be a valuable tool for lead optimization.