Synthesis and In Vitro Evaluation of Adenosine Deaminase Resistant N-6 Aminal and Thioaminal Prodrugs of Cordycepin

Hui-Min      Chang; Jesse      Oakes; Anders      Olsson; Luminita      Panaitescu; B.   Mark   Britt; Christopher   M.   Kearney; Robert   R.   Kane

Abstract

Cordycepin (3;-deoxyadenosine) is a potent anti-leukemic, anti-fungal, and anti-parasitic nucleoside antibiotic. Unfortunately, the biological activity of cordycepin is attenuated by its rapid conversion to 3;-deoxyinosine by adenosine deaminase (ADA). We have synthesized a series of ADA-resistant N-aminal and N-thioaminal cordycepin derivatives, which are protected from inactivation by deamination and yet retain biological activity. These compounds are hydrolyzed at various rates to efficiently release the parent drug cordycepin, and likely serve as simple hydrolytically activated prodrugs.

Keywords: cordycepin, adenosine deaminase, leukemia, prodrug

« Previous Next »

Rights & Permissions Print Cite

Letters in Drug Design & Discovery

Title: Synthesis and In Vitro Evaluation of Adenosine Deaminase Resistant N-6 Aminal and Thioaminal Prodrugs of Cordycepin

Volume: 2 Issue: 2

Author(s): Hui-Min Chang, Jesse Oakes, Anders Olsson, Luminita Panaitescu, B. Mark Britt, Christopher M. Kearney and Robert R. Kane

Affiliation:

Keywords: cordycepin, adenosine deaminase, leukemia, prodrug

Abstract: Cordycepin (3;-deoxyadenosine) is a potent anti-leukemic, anti-fungal, and anti-parasitic nucleoside antibiotic. Unfortunately, the biological activity of cordycepin is attenuated by its rapid conversion to 3;-deoxyinosine by adenosine deaminase (ADA). We have synthesized a series of ADA-resistant N-aminal and N-thioaminal cordycepin derivatives, which are protected from inactivation by deamination and yet retain biological activity. These compounds are hydrolyzed at various rates to efficiently release the parent drug cordycepin, and likely serve as simple hydrolytically activated prodrugs.

Export Options

Export File:

RIS (for EndNote, Reference Manager, ProCite)

BibTeX

Text

Content:

Citation Only

Citation and Abstract

About this article

Cite this article as:

Chang Hui-Min, Oakes Jesse, Olsson Anders, Panaitescu Luminita, Britt Mark B., Kearney M. Christopher and Kane R. Robert, Synthesis and In Vitro Evaluation of Adenosine Deaminase Resistant N-6 Aminal and Thioaminal Prodrugs of Cordycepin, Letters in Drug Design & Discovery 2005; 2 (2) . https://dx.doi.org/10.2174/1570180053175151