Synthesis and screening of 6-alkoxy purine analogs as cell type-selective apoptotic inducers in Jurkat cells.

Autor: Lorente-Macías Á; Department of Medicinal & Organic Chemistry and Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Granada, Spain.; Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain., Iañez I; Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain., Jiménez-López MC; Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain., Benítez-Quesada M; Department of Medicinal & Organic Chemistry and Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Granada, Spain., Torres-Rusillo S; Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain., Díaz-Mochón JJ; Department of Medicinal & Organic Chemistry and Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Granada, Spain., Molina IJ; Institute of Biopathology and Regenerative Medicine, University of Granada, Granada, Spain., Pineda de Las Infantas MJ; Department of Medicinal & Organic Chemistry and Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Granada, Spain.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2021 Oct; Vol. 354 (10), pp. e2100095. Date of Electronic Publication: 2021 Jun 15.
DOI: 10.1002/ardp.202100095
Abstrakt: Purines are ubiquitous structures in cell biology involved in a multitude of cellular processes, because of which substituted purines and analogs are considered excellent scaffolds in drug design. In this study, we explored the key structural features of a purine-based proapoptotic hit, 8-tert-butyl-9-phenyl-6-benzyloxy-9H-purine (1), by setting up a library of 6-alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based on cell cycle analysis of a panel of six human cancer cell lines, including T cell leukemia Jurkat cells. From this study, two derivatives (12 and 13) were identified as Jurkat-selective proapoptotic compounds, displaying superior potency and cell selectivity than hit 1.
(© 2021 The Authors. Archiv der Pharmazie published by Wiley-VCH Verlag GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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