Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that is characterized by progressive loss of the upper and lower motor neurons at the spinal or bulbar level. Oxidative stress (OS) associated with mitochondrial dysfunction and the deterioration of the electron transport chain are factors that contribute to neurodegeneration and perform a potential role in the pathogenesis of ALS. Natural antioxidant molecules have been proposed as an alternative form of treatment for the prevention of age-related neurological diseases, in which ALS is included. Researches support that regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in this disease, and antioxidant drugs are aimed at a promising pathway to treatment. Among the strategies used for obtaining new drugs, we can highlight the isolation of secondary metabolite compounds from natural sources that, along with semisynthetic derivatives, correspond to approximately 40% of the drugs found on the market. Among these compounds, we emphasize oxygenated and nitrogenous compounds, such as flavonoids, coumarins, and alkaloids, in addition to the fatty acids, that already stand out in the literature for their antioxidant properties, consisting in a part of the diets of millions of people worldwide. Therefore, this review is aimed at presenting and summarizing the main articles published within the last years, which represent the therapeutic potential of antioxidant compounds of natural origin for the treatment of ALS.
The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.
Gastric cancer is the fifth most common and fourth type to cause the highest mortality rates worldwide. The leading cause is related to Helicobacter pylori (H. pylori) infection. Unfortunately, current treatments have low success rates, highlighting the need for alternative treatments against carcinogenic agents, specifically H. pylori. Noteworthy, natural origin products contain pharmacologically active metabolites such as flavonoids, with potential antimicrobial applications.Objective: This article overviews flavonoid-rich extracts’ biological and pharmacological activities. It focuses on using these substances against Helicobacter pylori infection to prevent gastric cancer. For this, PubMed and Science Direct databases were searched for studies that reported the activity of flavonoids against H. pylori, published within a 10-year time frame (2010 to August 2020). It resulted in 1,773 publications, of which 44 were selected according to the search criteria. The plant family primarily found in publications was Fabaceae (9.61%). Among the flavonoids identified after extraction, the most prevalent were quercetin (19.61%), catechin (13.72), epicatechin (11.76), and rutin (11.76). The potential mechanisms associated with anti-H. pylori activity to the extracts were: inhibition of urease, damage to genetic material, inhibition of protein synthesis, and adhesion of the microorganism to host cells.Conclusion: Plant extracts rich in flavonoids with anti-H. pylori potential proved to be a promising alternative therapy source, reinforcing the relevance of studies with natural products.
Topoisomerase inhibitors are extensively used in cancer chemotherapy. In the process of identifying novel anticancer compounds, biological evaluations are crucial and include, among others, the use of in silico and in vitro approaches. This work aimed to present recent research involving the obtainment and in silico and in vitro evaluation of topoisomerase I, II, and double inhibitors, of synthetic and natural origin, as potential compounds against tumor cells, in addition to proposing the construction of a desirable enzyme catalytic site. Therefore, it was observed that most Topoisomerase I inhibitors presented medium to large structures, with a rigid portion and a flexible region. In contrast, Topoisomerase IIα inhibitors showed medium and large structural characteristics, in addition to the planarity of the aromatic rings, which is mitigated due to flexible rings, but may also present elements that restrict conformation. The majority of compounds that exhibit dual inhibitory activity had relatively long chains, in addition to a flat and rigid portion suggestive of affinity for Topo I, and a flexible region characteristic of selective drugs for Topo II. Besides, it is noticed that most compounds that exhibit dual inhibitory showed similarities in the types of interactions and amino acids when compared to the selective compounds of Topo I and II. For instance, selective Topoisomerase I inhibitors interact with Arginine364 residues and selective Topoisomerase II inhibitors interact with Arginine487 residues, as both residues are targets for dual compounds.
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