A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg(-1) day(-1) for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N(2),N(4)-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216219 | PMC |
| http://dx.doi.org/10.1021/jm5000408 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular modelling and optimization of a high-affinity nanobody targeting the nipah virus fusion protein through in silico site-directed mutagenesis.
Comput Biol Chem
January 2025
Virology and Vaccine Research and Development Program, Department of Science and Technology-Industrial Technology Development Institute, Taguig City, Metro Manila 1631, Philippines; S&T Fellows Program, Department of Science and Technology, Taguig City, Metro Manila 1631, Philippines; Department of Biology, College of Arts and Sciences, University of the Philippines - Manila, Metro Manila 1000, Philippines. Electronic address:
Nipah virus (NiV) is a re-emerging zoonotic pathogen with a high mortality rate and no effective treatments, prompting the search for new antiviral strategies. While conventional antiviral drugs are often limited by issues such as poor specificity, off-target effects, and resistance development, nanobodies offer distinct advantages. These small, single-domain antibodies exhibit high specificity and stability, making them ideal candidates for antiviral therapy.
View Article and Find Full Text PDFValorization of Cocoa and Peach-Palm Wastes for the Production of Amylases by Pleurotus pulmonarius CCB19 and Its Application as an Additive in Commercial Detergents.
Appl Biochem Biotechnol
January 2025
Department of Biological Sciences, UESC - Universidade Estadual de Santa Cruz, Rodovia Jorge Amado, Km 16, Ilhéus, BA, 45662-900, Brazil.
In the context of agribusiness, the agricultural and livestock sectors generate a considerable quantity of waste on a daily basis. Solid-state fermentation (SSF) represents a potential alternative for mitigating the adverse effects of residue accumulation and for producing high-value products such as enzymes. Pleurotus pulmonarius is capable of producing a number of commercial enzymes, including amylases.
View Article and Find Full Text PDFA Cost-Effective Nonaqueous Reversed-Phase High-Performance Liquid Chromatography Method to Measure Vitamin D3 in Hen's Egg Yolk.
J Sep Sci
January 2025
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
The objective of this study is to develop an HPLC-UV method for the cost-effective and quantitative determination of vitamin D3 in food, even in the presence of vitamin D2, with a specific focus on egg yolk. During method development, the performance of three stationary phases in resolving the peak of vitamin D2 from that of vitamin D3 was investigated. The physicochemical properties of these phases differed particularly in the extent of hydrophobicity and silanophilic activity, including a GraceSmart RP C18 column without silanol endcapping, a Robusta RP C18 column with silanol endcapping, and a Waters Xbridge RP C18 column with ethylene-bridged hybrid (BEH) particle technology.
View Article and Find Full Text PDFIsolation, characterization and therapeutic efficacy of lytic bacteriophage ZK22 against Salmonella Typhimurium in mice.
BMC Microbiol
January 2025
Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, Guangdong, China.
Background: Salmonella enterica serovar Typhimurium is one of the most common serovars of Salmonella associated with clinical cases. It not only leads to diarrhea and mortality raised in livestock and poultry farming, but also poses a risk to food safety.
Results: In this study, a lytic bacteriophage named ZK22 was isolated and identified from sewage.
Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis.
Sci Rep
January 2025
Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, 59064-741, RN, Brazil.
The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro.
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!