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A series of congeners structurally related to pritelivir, N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide, a helicase-primase inhibitor for the treatment of herpes simplex virus infections, was prepared. The synthesized primary and secondary sulfonamides were investigated as inhibitors of six physiologically and pharmacologically relevant human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, the cytosolic enzymes hCA I and II, the mitochondrial ones hCA VA and VB, and the transmembrane, tumor associated hCA IX and XII. Low nanomolar inhibition KI values were detected for all of them, with a very interesting and well-defined structure–activity relationship. As many CAs are involved in serious pathologies, among which are cancer, obesity, epilepsy, glaucoma, etc., sulfonamide inhibitors as those reported here may be of interest as drug candidates. Furthermore, pritelivir itself is an effective inhibitor of some CAs, also inhibiting whole blood enzymes from seve...

A fully automated microfluidic system was developed to screen for novel anti-HBV capsid assembly modulators. High-resolution dose–response curves were generated using convection-dominated Taylor–Aris dispersion of the screening compounds.

This chapter by choosing the field of neglected tropical diseases (NTDs) as the background therapeutic area describes efforts to develop multitarget drugs for solving the vexing medical problem. Among the various NTDs, the chapter focuses on three diseases most significant in terms of morbidity and mortality: human African trypanosomiasis (HAT), Chagas' disease, and leishmaniasis. A numerous class of hybrid anti‐trypanosomatid molecules is represented by the so‐called targeted drugs, which combine a framework with antiparasitic activity with a fragment recognized by a parasite transporter. A multitarget‐directed ligand (MTDL) is a single chemical entity that simultaneously recognizes different targets inside the parasite. The chapter then presents the report on the different approaches that are exploited to obtain innovative hybrid small molecules. Modern drug discovery for NTDs is carried out using both target‐based and phenotypic approaches. The target‐based approaches to NTDs are a widely used route for drug discovery programs aimed at identifying new lead compounds for diseases.