Guinan, M, Huang, N, Hawes, CS, Lima, MA, Smith, M and Miller, GJ (2021) Chemical synthesis of 4'-thio and 4'-sulfinyl pyrimidine nucleoside analogues. Organic & Biomolecular Chemistry. ISSN 1477-0520

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Analogues of the canonical nucleosides required for nucleic acid synthesis have a longstanding presence and proven capability within antiviral and anticancer research. 4'-Thionucleosides, that incorporate bioisosteric replacement of furanose oxygen with sulfur, represent an important chemotype within this field. Established herein is synthetic capability towards a common 4-thioribose building block that enables access to thio-ribo and thio-arabino pyrimidine nucleosides, alongside their 4'-sulfinyl derivatives. In addition, this building block methodology is templated to deliver 4'-thio and 4'-sulfinyl analogues of the established anticancer drug gemcitabine. Cytotoxic capability of these new analogues is evaluated against human pancreatic cancer and human primary glioblastoma cell lines, with observed activities ranging from low μM to >200 μM; explanation for this reduced activity, compared to established nucleoside analogues, is yet unclear. Access to these chemotypes, with thiohemiaminal linkages, will enable a wider exploration of purine and triphosphate analogues and the application of such materials for potential resistance towards relevant hydrolytic enzymes within nucleic acid biochemistries.

Item Type: Article
Additional Information: Open Access Article. Published on 11 November 2021. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QD Chemistry > QD415 Biochemistry
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 21 Dec 2021 16:32
Last Modified: 14 Feb 2022 09:32

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