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

No Thumbnail Available

Date

2021-06-15

Authors

Lorente-Macías, Álvaro
Iañez, Inmaculada
Jiménez-López, M Carmen
Benítez-Quesada, Manuel
Torres-Rusillo, Sara
Díaz-Mochón, Juan J
Molina, Ignacio J
Pineda de Las Infantas, María J

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

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.

Description

MeSH Terms

Antineoplastic Agents
Apoptosis
Cell Line, Tumor
Humans
Jurkat Cells
Leukemia, T-Cell
Purines
Structure-Activity Relationship

DeCS Terms

CIE Terms

Keywords

anticancer drugs, apoptosis, leukemia, phenotypic screening, purine analogs

Citation