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CRISPR/gene editing methods and covalent inhibitors/chemoproteomic probes are also topics to be included in this issue. With this call for papers, our readers can expect new assays and techniques using fluorescent molecules and proteins for imaging, new probes for clinical imaging, new small molecule PET ligands with high specificity, new techniques for live cell and whole animal imaging, and finally, new high content imaging methods in assay development. In 2022, I ASSAY and Drug Development Technologies i , in continuation with Dr. Milka Kostic as guest editor, is forging ahead with our issue series on Chemical Probes and Pharmacological Tools. [Extracted from the article]

• Developed a simple fluorometric and target-free method for primary drug screening • 2,4-diaminoquinazoline scaffold has activity against two Leishmania spp. • Scaffold exhibits varying selectivity against target cells in vitro and in vivo • Scaffold is appropriate for cutaneous leishmaniasis and topical development Leishmania parasites are the causative agents of a wide spectrum of human diseases. The clinical manifestations of leishmaniasis range from self-healing skin lesions to fatality. The World Health Organization has classed leishmaniasis as a category 1 neglected tropical disease. Leishmaniasis represents a major international health challenge, affecting 12 million people per year and with nearly 310 million people at risk. The first-line chemotherapies used to treat leishmaniasis are intravenous pentavalent antimonials; however, these drugs are highly toxic. As the use of oral treatment options such as paromomycin and miltefosine has increased, the incidence of disease relapse has increased and drug resistance to antimonials has developed, emphasizing the importance of identifying new chemotherapies. A novel, target-free fluorometric high-throughput screen with an average Z-score of 0.73 +/- 0.13 has been developed to identify small molecules with antileishmanial activity. Screening of 10,000 small molecules from the ChemBridge DIVER-set™ library cassette #5 yielded 210 compounds that killed 80% of parasites, resulting in a hit rate of 2.1%. One hundred and nine molecular scaffolds were represented within the hit compounds, and one scaffold that exhibited potent antileishmanial activity was 2,4-diaminoquinazoline. Host cell toxicity was determined prior to in-vitro infection of human THP-1 macrophages with Leishmania donovani mCherry expressing promastigotes; successful drug treatment was considered when the half maximal inhibitory concentration was <10 µM. BALB/c mice were infected with Leishmania major mCherry promastigotes and treated with small molecules that were successful during in-vitro infections. Several small molecules tested were as efficacious at resolving cutaneous leishmaniasis lesions in mice as known antimonial treatments. Image, graphical abstract [ABSTRACT FROM AUTHOR]