Influence of 4'-Substitution on the Activity of Gemcitabine and Its ProTide Against VZV and SARS-CoV-2.
ACS Med Chem Lett
; 12(1): 88-92, 2021 Jan 14.
Article
in English
| MEDLINE | ID: covidwho-997790
ABSTRACT
In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4'-methoxy- and 4'-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4'-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC50 of 0.042 µM and produced significant cytotoxicity (CC50 = 0.11 µM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC50 = 0.73 µM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.
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MEDLINE
Language:
English
Journal:
ACS Med Chem Lett
Year:
2021
Document Type:
Article
Affiliation country:
Acsmedchemlett.0c00485
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