Synthesis and biological activity against Mycobacterium tuberculosis of 2,3-dihydroadenine derivatives

Abstract

Purines have attracted attention of the scientific community mainly due to their biological activity [1]. During the last decade, purine derivatives were identified as a promising new class of antitubercular agents. The research was focused on the synthesis of nucleoside analogues as siderophore biosynthesis inhibitors [2], and on non-nucleosides [3]. In the non-nucleoside series, purines having an aryl, a small alkyl or a proton as the 9-N substituent were essentially inactive, whereas 9-benzyl-6-(2-furyl)purines [3a,c,d], 9-sulfonyl-6-mercaptopurines or 6-alkylthiopurines [3b,e] were highly potent. In addition, we recently described the first example of 2,9-diarylpurines active against Mycobacterium tuberculosis (Mtb) [4]. In order to perform SAR studies in the new scaffold, we synthesized novel 2,3-dihydroadenine derivatives. These new molecules represent valuable targets as they possess all the sub units present in the 2-phenolic adenine derivatives that showed activity against Mtb however they allow new conformations. The synthesis of the new derivatives and the biological results obtained against Mtb will be presented.