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Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC50) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC50) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the most studied progressive eurodegenerative disorder, affecting 40-50 million of the global population. This progressive neurodegenerative disease is marked by gradual and irreversible declines in cognitive functions. The unavailability of therapeutic drug candidates restricting/reversing the progression of this dementia has severed the existing challenge. The development of acetylcholinesterase (AChE) inhibitors retains a great research focus for the discovery of an anti-Alzheimer drug. Materials and methods: This study focused on finding AChE inhibitors by applying the machine learning (ML) predictive modeling approach, which is an integral part of the current drug discovery process. In this study, we have extensively utilized ML and other in silico approaches to search for an effective lead molecule against AChE. Result and discussion: The output of this study helped us to identify some promising AChE inhibitors. The selected compounds performed well at different levels of analysis and may provide a possible pathway for the future design of potent AChE inhibitors. [ABSTRACT FROM AUTHOR]

Leishmaniasis, caused by Leishmania parasites, presents a major global health challenge due to limitations of existing treatments, including toxicity, side effects, drug resistance, and high costs. This study utilized the MuDRA (Multi-Descriptor Read Across) model for virtual screening to identify potential anti-Leishmania infantum compounds. A set of 15 terpenes and steroids was screened, leading to the identification of four promising candidates-lupeol, xylodiol, morolic acid, and trachyloban-18-oic acid. These compounds demonstrated significant activity in both virtual screening and in vitro assays. To elucidate their potential mechanisms of action, we conducted molecular docking and dynamics studies, which revealed stable interactions with key target enzymes, such as trypanothione reductase and 14-alpha demethylase (CYP51), crucial to the parasite's survival and pathogenesis. These findings provide valuable insights into novel mechanisms for targeting leishmaniasis, offering a promising basis for the development of new therapeutics. The integration of computational and experimental methods in this study not only advances our understanding of potential anti-leishmanial agents but also highlights the effectiveness of this approach in discovering new drugs for neglected diseases. Further in vivo studies and clinical trials will be essential to validate the therapeutic potential of these., (© 2024 Wiley‐VCH GmbH.)

Background: Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessel diseases. Several studies have been conducted to identify antithrombotic agents from medicinal plants, and phenolic compounds (PCs) have been shown to effectively inhibit plasma coagulation and platelet aggregation., Objectives: This study aimed to conduct a survey of the natural PCs with proven antithrombotic and antiplatelet activities, as well as to evaluate by computational modeling the physicochemical and toxicological properties of these compounds using drug-likeness approaches., Methods: The data were collected from the scientific database: ' Web of Science', 'Scifinder', 'Pubmed', 'ScienceDirect' and 'Google Scholar' , the different classes of PCs with antithrombotic or antiplatelet effects were used as keywords. These molecules were also evaluated for their Drug-Likeness properties and toxicity to verify their profile for being candidates for new antithrombotic drugs., Results: In this review, it was possible to register 85 lignans, 73 flavonoids, 28 coumarins, 21 quinones, 23 phenolic acids, 8 xanthones and 8 simple phenols. Activity records for tannins were not found in the researched databases. Of these 246 compounds, 213 did not violate any of Lipinski's rules of five, of which 125 (59%) showed non-toxicity, being promising candidates for new potential antithrombotic drugs., Conclusion: This review arouses interest in the isolation of phenolic compounds that may allow a new approach for the prevention of both arterial and venous thrombosis, with the potential to become alternatives in the prevention and treatment of cardiovascular diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Natural products are useful agents for the discovery of new lead- compounds and effective drugs to combat coronaviruses (CoV)., Objective: The present work provides an overview of natural substances, plant extracts, and essential oils as potential anti-SARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process., Methods: The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analysis were obtained in alvaDesc and the principal component analysis (PCA) was carried out in SIMCA version 13.0., Results: Based on in vitro assays and computational analyses, this review covers twentynine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes are the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity., Conclusion: This paper highlights the role of ethnopharmacology in drug discovery and suggests the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antiviral agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)