Abstract
Title 6-alkyl-, 6-aryl- and 6-hetaryl-7-deazapurine ribonucleosides previously known as nanomolar cytostatics were found to be potent inhibitors of either human or mycobacterial (MTB) adenosine kinase (ADK). Several new derivatives bearing bulky substituents at position 6 were non-cytotoxic but selectively inhibited MTB ADK. However, most of the nucleosides (ADK inhibitors) as well as their octadecylphosphate prodrugs were inactive in the whole cell assay of inhibition of Mycobacterium bovis growth. 6-Methyl-7-deazapurine ribonucleoside was found to be a potent antimycobacterial agent.
Highlights
Modi ed purine nucleoside derivatives and analogs display a wide range of biological activities
In order to get less cytotoxic derivatives, we have extended the series by synthesis of other six derivatives bearing bulkyaryl groups at position 6 (Scheme 1)
The other derivatives 1w–z were synthesized by direct aqueous Suzuki coupling of 6-chloro-7-deazapurine ribonucleoside with the corresponding hetarylboronic acid in the presence of Pd(OAc)[2], triphenylphosphine-3,30,300-trisulfonate (TPPTS) and Na2CO3
Summary
Modi ed purine nucleoside derivatives and analogs display a wide range of biological activities. Diverse aryl and hetaryl groups at position 6 and systematically studied their activity toward human and MTB ADKs. Results and discussion In order to get less cytotoxic derivatives, we have extended the series by synthesis of other six derivatives bearing bulky (het)aryl groups at position 6 (Scheme 1).
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