Pertusati, Fabrizio  ORCID: https://orcid.org/0000-0003-4532-9101, Hinsinger, Karen, Flynn, Áine Sinéad, Powell, Ned George, Tristram, Amanda Jane, Balzarini, Jan and McGuigan, Christopher ORCID: https://orcid.org/0000-0001-8409-710X
2014.
PMPA and PMEA prodrugs for the treatment of HIV infections and human papillomavirus (HPV) associated neoplasia and cancer.
European Journal of Medicinal Chemistry
78
, pp. 259-268.
10.1016/j.ejmech.2014.03.051
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Abstract
The synthesis and in vitro biological evaluation of novel phosphonamidate and phosphonodiamidate prodrugs of adefovir and tenofovir are reported. The selected synthetic approach from free phosphonic acid via bis-trimethylsilyl ester intermediates affords (l)-alanine ester derivatives in 10–70% yields. When assessed for their anti-HIV activity, all the prodrugs showed submicromolar activity. Noteworthy, the most potent derivative in the adefovir series contained a 5,6,7,8-tetrahydronaphtyl group, herein reported for the first time as an aryl moiety in a ProTide. A pronounced cytostatic activity of the above prodrugs is also reported. Selected compounds were tested for their antiproliferative activity against HPV-transformed cells and they were found significantly more active in comparison to their parent compounds. In this study a slightly improved activity of the adefovir derivatives over those of tenofovir was also noticed. However, no specificity for naturally HPV-transformed cell lines was observed.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Schools > Pharmacy Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Uncontrolled Keywords: | 5,6,7,8-Tetrahydro-1-naphthol; HIV; Antiproliferative activity; HPV; PMPA/PMEA |
| Publisher: | Elsevier |
| ISSN: | 0223-5234 |
| Date of First Compliant Deposit: | 30 March 2016 |
| Date of Acceptance: | 15 March 2014 |
| Last Modified: | 11 Nov 2024 18:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/59063 |
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