A series of highly active hybrids were discovered as novel antiparasitic agents. Two heterocyclic scaffolds (1,2,4-oxadiazole and 3-hydroxy-2-oxindole) were linked, and the resulting compounds showed in vitro activities against intracellular amastigotes of two protozoan parasites, Trypanosoma cruzi and Leishmania infantum. Their cytotoxicity was assessed using HFF-1 fibroblasts and HepG2 hepatocytes. Compounds 5b, 5d, 8h and 8o showed selectivity against L. infantum (IC values of 3.89, 2.38, 2.50 and 2.85 μM, respectively). Compounds 4c, 4q, 8a and 8k were the most potent against T. cruzi, exhibiting IC values of 6.20, 2.20, 2.30 and 2.20 μM, respectively. Additionally, the most potent anti-T. cruzi compounds showed in vitro efficacies comparable or superior to that of benznidazole. These easy-to-synthesize molecules represent novel chemotypes for the design of potent and selective lead compounds for Chagas disease and leishmaniasis drug discovery.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2020.112418 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluation of an indirect Na1.7 inhibitor as adjunctive analgesic in burn-related neuropathic pain in a cat.
Vet Anaesth Analg
January 2025
Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, FL, USA.
Burn-related neuropathic pain (BRNP) can arise following burn-induced nerve damage, affects approximately 6% of burned human patients and can result in chronic pain. Although widely studied in humans, data on BRNP or its treatment in animals is lacking. A 4-year-old domestic shorthair cat was presented with an infected, non-healing wound suspected to be a caustic burn.
View Article and Find Full Text PDFPharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.
Pharmaceutics
December 2024
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC = 30 nM).
View Article and Find Full Text PDFExtraction and Processing of Bioactive Phytoconstituents from Widely Used South African Medicinal Plants for the Preparation of Effective Traditional Herbal Medicine Products: A Narrative Review.
Plants (Basel)
January 2025
Traditional Medicine Laboratory, University of KwaZulu Natal, Durban 4041, South Africa.
Medicinal plants are sources of crude traditional herbal medicines that are utilized to reduce the risk of, treat, or manage diseases in most indigenous communities. This is due to their potent antioxidant and anti-inflammatory effects. It is estimated that about 80% of the population in developing countries rely on herbal traditional medicines for healthcare.
View Article and Find Full Text PDF()-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer.
Pharmaceuticals (Basel)
January 2025
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland.
The synthesis of ()-1-(1,3-diphenylallyl)-1-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. : A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition.
View Article and Find Full Text PDFAnti-Biofilm Agents to Overcome Antibiotic Resistance.
Pharmaceuticals (Basel)
January 2025
AGIR, UR 4294, Faculté de Pharmacie, Université de Picardie Jules Verne, 1 Rue des Louvels, 80000 Amiens, France.
is one of world's most threatening bacteria. In addition to the emerging prevalence of multi-drug resistant (MDR) strains, the bacterium also possesses a wide variety of virulence traits that worsen the course of the infections. Particularly, its ability to form biofilms that protect colonies from antimicrobial agents is a major cause of chronic and hard-to-treat infections in immune-compromised patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!