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Inhibition of Adenosine Deaminase by Analogues of Adenosine and Inosine, Incorporating a Common Heterocyclic Base, 4(7)-Amino-6(5)H-imidazo[4,5-d]pyridazin-7(4)one

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posted on 2008-02-14, 00:00 authored by Ravi K. Ujjinamatada, Pornima Phatak, Angelika M. Burger, Ramachandra S. Hosmane
Four nucleoside analogues (14) containing a common heterocyclic base, 4(7)-amino-6(5)H-imidazo[4,5-d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with Ki values of 10–12 µM are more than four times as potent inhibitors of ADA compared with 2 and 4, with Ki values of 51–52 µM. Also, 3 is not a substrate of ADA. Nucleosides 3 and 4 also exhibit moderate in vitro activity against breast cancer cell lines, while all four are only minimally or nontoxic to the normal cells.

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