The Search for Drugs Derived from Natural Products for Infection Treatment in the Last 20 Years - A Systematic Review.

Introduction: Toxoplasmosis is a worldwide distributed zoonosis caused by ), an obligate intracellular protozoan. The infection in immunocompetent hosts usually progresses with mild or no symptoms. However, in immunocompromised individuals, this disease can cause severe or fatal symptoms.

Potential of Ocotea indecora (Schott) Mez essential oil nanoemulsion in schistosomiasis control: Molluscicidal effects.

Schistosomiasis is a neglected disease transmitted through contaminated water in populations with low basic sanitation. The World Health Organization recommends controlling the intermediate host snails of the Biomphalaria genus with the molluscicide niclosamide. This work aims to evaluate the biocidal potential of the nanoemulsion prepared with the essential oil of Ocotea indecora leaves for the control of the mollusk Biomphalaria glabrata, intermediate host of the Schistosoma mansoni, the etiologic agent of schistosomiasis.

In vitro evaluation of 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against replicative and infective stages of Trypanosoma cruzi.

Current treatment of Chagas disease (CD) is based on two substances, nifurtimox (NT) and benzonidazole (BZ), both considered unsatisfactory mainly due to their low activities and high toxicity profile. One of the main challenges faced in CD management concerns the identification of new drugs active in the acute and chronic phases and with good pharmacokinetic profiles. In this work, we studied the bioactivity of twenty 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against Trypanosoma cruzi epimastigotes and trypomastigotes.

Molluscicidal and Cercaricidal Effects of Essential Oil Nanoemulsion.

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents.

Synthetic molecules as P2X7 receptor antagonists: A medicinal chemistry update focusing the therapy of inflammatory diseases.

Stimulation of the P2X7 receptor by extracellular adenosine 5'-triphosphate induces a series of responses in the organism, exceptionally protein cascades related to the proinflammatory process. This has made P2X7 a target for research on inflammatory diseases such as rheumatoid arthritis. Thus, the incessant search for new prototypes that aim to antagonize the action of P2X7 has been remarkable in recent decades, a factor that has already led to numerous clinical studies in humans.

Inclusion complex of O-allyl-lawsone with 2-hydroxypropyl-β-cyclodextrin: Preparation, physical characterization, antiparasitic and antifungal activity.

The subclass naphthoquinone represents a substance group containing several compounds with important activities against various pathogenic microorganisms. Accordingly, we evaluated O-allyl-lawsone (OAL) antiparasitic and antifungal activity free and encapsulated in 2-hydroxypropyl-β-cyclodextrin (OAL MKN) against Trypanosoma cruzi and Sporothrix spp. OAL and OAL MKN were synthesized and characterized by physicochemical methods.

In silico and pharmacological study of N,S-acetal juglone derivatives as inhibitors of the P2X7 receptor-promoted in vitro and in vivo inflammatory response.

Purinergic receptors are transmembrane proteins responsive to extracellular nucleotides and are expressed by several cell types throughout the human body. Among all identified subtypes, the P2×7 receptor has emerged as a relevant target for the treatment of inflammatory disease. Several clinical trials have been conducted to evaluate the effectiveness of P2×7R antagonists.

Molluskicidal nanoemulsion of (DC.) N. Silveira for schistosomiasis control.

Schistosomiasis is caused by the parasite , which uses mollusks of the genus as intermediate hosts. In 2020, approximately 241 million people worldwide underwent treatment for schistosomiasis. For this reason, the World Health Organization encourages research on alternative molluskicides based on plant species.

Synthesis, Biological Evaluation and Molecular Modeling Studies of Naphthoquinone Sulfonamides and Sulfonate Ester Derivatives as P2X7 Inhibitors.

ATP acts in the extracellular environment as an important signal, activating a family of receptors called purinergic receptors. In recent years, interest in the potential therapeutics of purinergic components, including agonists and antagonists of receptors, has increased. Currently, many observations have indicated that ATP acts as an important mediator of inflammatory responses and, when found in high concentrations in the extracellular space, is related to the activation of the P2X7 purinergic receptor.

Triazoles with inhibitory action on P2X7R impaired the acute inflammatory response in vivo and modulated the hemostatic balance in vitro and ex vivo.

Objective: The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo.

Material: The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12.

Treatment: We administered 500 ng/kg triazole analogs in vivo, (1-10 µM) in vitro, and 1000 mg/kg for toxicological assays.

Simulated hypoxia modulates P2X7 receptor function in mice peritoneal macrophages.

The inflammatory focus is similar to the tumor microenvironment, which contains a complex milieu with immune cells and macrophages. The accumulation of cells promotes local pH and O tension decline (hypoxia). Local O tension decline activates hypoxia-inducible factor α and β (HIF-1α and HIF-1β adenosine triphosphate (ATP) release.

Nanoemulsion of as an Alternative to Combat Schistosomiasis.

Schistosomiasis is caused by the intestinal parasite . Individuals are affected by schistosomiasis when they are exposed to aquatic environments contaminated with that emerged from the infected intermediate host mollusk of the genus . The WHO recommends using molluscicidal products to reduce the snail population and disease transmission.

Molluskicidal activity of 3-aryl-2-hydroxy-1,4-naphthoquinones against Biomphalaria glabrata.

Schistosomiasis is the second most prevalent parasitic infectious disease after malaria, which affects millions of people worldwide and causes health and socioeconomic problems. The snail Biomphalaria glabrata is an intermediate host for the helminth, which is the causative agent of schistosomiasis: Schistosoma mansoni. One crucial strategy for controlling the disease is the eradication of the snail host.

Semisynthetic triterpenes led to the generation of selective antitrypanosomal lead compounds.

Triterpenes α,β-amyrin are naturally occurring molecules that can serve as building blocks for synthesizing new chemical entities. This study synthesized acyl, carboxyesther, NSAID, and nitrogenous derivatives and evaluated their antimicrobial activity. A cyclodextrin complexation method was developed to improve the solubility of the derivatives.

Influence of purinergic signaling on glucose transporters: A possible mechanism against insulin resistance?

Metabolic disorders, such as insulin resistance, affect many people worldwide due to the prevalence of obesity and type 2 diabetes, which are pathologies that impair glycemic metabolism. Glucose is the primary energetic substrate of the body and is essential for cellular function. As the cell membrane is not permeable to glucose molecules, there are two distinct groups of glucose transporters: sodium-glucose-linked transporters (SGLTs) and the glucose transporter (GLUT) family.

P2X7 receptor inhibition by 2-amino-3-aryl-1,4-naphthoquinones.

Extracellular ATP activates purinergic receptors such as P2X7, cationic channels for Ca, K, and Na. There is robust evidence of the involvement of these receptors in the immune response, so P2X7 receptors (P2X7R) are considered a potential therapeutic target for the development of anti-inflammatory drugs. Although there are many studies of the anti-inflammatory properties of naphthoquinones, these molecules have not yet been explored as P2X7 antagonists.

Anti-Bronchospasmodic Effect of JME-173, a Novel Mexiletine Analog Endowed With Highly Attenuated Anesthetic Activity.

Local anesthetics (LAs), such as lidocaine and mexiletine, inhibit bronchoconstriction in asthmatics, but adverse effects limit their use for this specific clinical application. In this study, we describe the anti-spasmodic properties of the mexiletine analog 2-(2-aminopropoxy)-3,5-dimethyl, 4-Br-benzene (JME-173), which was synthesized and screened for inducing reduced activity on Na channels. The effectiveness of JME-173 was assessed using rat tracheal rings, a GH3 cell line and mouse cardiomyocytes to access changes in smooth muscle contraction, and Na, and Caionic currents, respectively.

Plant natural products as source of new P2 receptors ligands.

In recent years, interest in the research of P2 receptor (P2R)-mediated responses has grown significantly due to the recognition of the involvement of these receptors in various physiological and pathological processes. Despite all the progress made in the functional characterization of P2Rs, purinergic signaling research is still limited by the lack of selective or efficient ligands for different receptor subtypes. In this sense, several molecules have been tested towards these receptors as agonists or antagonists.

Capsaicin: TRPV1-independent mechanisms and novel therapeutic possibilities.

Capsaicin (CAP) is a spice-derived substance of the genus Capsicum, which has high pungency and therapeutic potential. For many years, it has been considered only as an agonist of the transient receptor potential vanilloid member 1 (TRPV1), a member from the family of transient potential receptors (TRPs). Capsaicin can lead to a variety of effects on cells, acting in specific organelles, and promoting different responses.

Pharmacological profiling of JME-173, a novel mexiletine derivative combining dual anti-inflammatory/anti-spasmodic functions and limited action in Na channels.

Existing evidence suggests that the local anaesthetic mexiletine can be beneficial for patients with asthma. However, caution is required since anaesthesia of the airways inhibits protective bronchodilator neuronal reflexes, limiting applications in conditions of hyperirritable airways. Here, we describe the synthesis of a new series of mexiletine analogues, which were screened for reduced activity in Na channels and improved smooth muscle relaxant effects, that were evaluated using the patch-clamp technique and an isolated tracheal organ bath, respectively.

Synthesis of new N,S-acetal analogs derived from juglone with cytotoxic activity against Trypanossoma cruzi.

A series of 11 new N,S-acetal juglone derivatives were synthesized and evaluated against T. cruzi epimastigote forms. These compounds were obtained in good to moderate yields using a microwave irradiation protocol.

Synthesis and biological evaluation of β-lapachone and nor-β-lapachone complexes with 2-hydroxypropyl-β-cyclodextrin as trypanocidal agents.

We study βLAP and its derivative nor-β-Lapachone (NβL) complexes with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and bioavailability. The formation of true inclusion complexes between βLAP or NβL in 2-HP-β-CD in solid solution was characterization by FT-IR, DSC, powder X-ray was and was confirmed by one- and two-dimensional H NMR experiments. Additionally, the biological activities of βLAP, NβL, ICβLAP, and ICNβL were investigated through trypanocidal assays with T.