Pavel Kraina

pavel.kraina@uochb.cas.cz

+420 220 183 262

Ph.D. student

Zlatko Janeba Group

Medicinal Chemistry of Nucleotide Analogues

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Selected papers

Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir

P. Kraina M. Česnek E. Tloušťová H. Mertlíková-Kaiserová C. J. Fulton E. K. Davidson B. P. Smith V. J. Watts Z. Janeba

Bioorganic & Medicinal Chemistry 95: 117508 (2023)

Adefovir based acyclic nucleoside phosphonates were previously shown to \nmodulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC₅₀ = 4.45 μM), non-toxic, and selective mAC2 inhibitor (vs. mAC1 and mAC5). Such a compound represents a valuable addition to a limited number of \nsmall-molecule probes to study the biological functions of individual endogenous mAC isoforms.

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