Abstract
A seriesof twenty four acyclic unsaturated 2,6-substututed purines 5a-20b were synthesized. These compounds were evaluated for cytotoxic activity against NCI-60 DTP human tumor cell line screen at 10µM concentration. N9-[(Z)-4'-chloro-2'-butenyl-1'-yl]-2,6-dichloropurine(5a), N9-[4'-chloro-2'-butynyl-1'-yl]-2,6-dichloropurine(10a), N9-[(E)-2',3'-dibromo-4'-chloro-2'-butenyl-1'-yl]-6-methoxypurine(14) and N9-[4'-chloro-2'-butynyl-1'-yl]-6-(4-methoxyphenyl)-purine(19) exhibited highly potent cytotoxic activity with GI50 values in the 1–5 µM range for most human tumor cell lines. Other compounds exhibited moderate activity.
Highlights
According to WHO report on cancer about 7.6 million people died in the year 2005 and the number is expected to raise to 9 million by the year 2015 and 11.5 million by 2030 [1]
The N9-alkylated compounds 5a-20b were prepared by the direct alkylation approach on the appropriately substituted purine bases in presence of K2CO3 in dimethyl formamide (DMF) medium (Schemes 1 and 2)
This suggests that 2,6dichloropurine base has significant potential for further work on the synthesis of anti-cancer compounds
Summary
According to WHO report on cancer about 7.6 million people died in the year 2005 and the number is expected to raise to 9 million by the year 2015 and 11.5 million by 2030 [1]. Development of new potent and selective anticancer agents has become one of most intensely pursued goals in drug development around the world. Neplanocin A, (1, Figure 1) is considered a carbocyclic analogue of a natural nucleoside and has shown potent antitumor and antiviral properties [2,3,4]. As a part of our research program on the synthesis of anti-cancer agents, we have synthesized some aromatic neplanocin-A analogues like 3a-3b, 4a-c [5,6,7]. 4a-4c (Figure 1), were found to be potent in vitro growth inhibitors of several human tumor cell lines. These results prompted us to consider purines with an unsaturated N9-linker that has been terminated with a chloromethyl group
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