title: Synthesis and antimycobacterial activities of non-purine analogs of 6-aryl-9-benzylpurines: Imidazopyridines, pyrrolopyridines, benzimidazoles, and indoles.
abstract: 6,9-Disubstituted purines and 7-deazapurines are known to be powerful inhibitors of Mycobacterium tuberculosis (Mtb) in vitro. Analogs modified in the six-membered ring (imidazopyridines, pyrrolopyridines, benzimidazoles, and indoles) were synthesized and evaluated as Mtb inhibitors. The targets were prepared by functionalization on the bicyclic heterocycle or from simple pyridines. The results reported herein, indicate that the purine N-1, but not N-3, is important for binding to the unknown target. The 3-deazapurines appears to be slightly more active compared to the parent purines and slightly less active than their 7-deazapurine isomers. Removal of both the purine N-3 and N-7 did not result in further enhanced antimycobacterial activity but the toxicity towards mammalian cells was increased. Both 3-deaza and 3,7-dideazapurines exhibited a modest activity against of the Mtb isolate in the state of non-replicating persistence.
authors.affiliation: Department of Chemistry, University of Oslo, Blindern, N-0315 Oslo, Norway.
authors.forename: Abhijit Datta
authors.initials: AD
authors.lastname: Khoje
authors.forename: Colin
authors.initials: C
authors.lastname: Charnock
authors.forename: Baojie
authors.initials: B
authors.lastname: Wan
authors.forename: Scott
authors.initials: S
authors.lastname: Franzblau
authors.forename: Lise-Lotte
authors.initials: LL
authors.lastname: Gundersen
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002522:Chlorocebus aethiops; D007093:Imidazoles / Q000737:chemistry; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011687:Purines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D001562:Benzimidazoles; D007093:Imidazoles; D007211:Indoles; D011687:Purines; D011725:Pyridines; C029899:imidazole; C030985:purine