5213-08-1Relevant articles and documents
Discovery and structure-activity relationships of modified salicylanilides as cell permeable inhibitors of poly(ADP-ribose) glycohydrolase (PARG)
Steffen, Jamin D.,Coyle, Donna L.,Damodaran, Komath,Beroza, Paul,Jacobson, Myron K.
experimental part, p. 5403 - 5413 (2011/10/02)
The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure-activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.
Synthesis and anti-staphylococcal activity of new halogenated pyrroles related to pyrrolomycins F
Raimondi, Maria Valeria,Schillaci, Domenico,Petruso, Salvatore
, p. 1407 - 1411 (2008/09/19)
(Chemical Equation Presented) The chemical synthesis of new halogenated pyrroles related to pyrrolomycins F is described and the anti-staphylococcal activity compared. The replacement of 4′-bromo atom of parent compounds with two chloro atoms at 3′ and 5′
Acyl derivatives of 2-aminobenzimidazole and their fungicide activity
Pilyugin,Sapozhnikov,Sapozhnikova
, p. 738 - 743 (2007/10/03)
Procedures have been developed for the preparation of methyl 2-benzimidazolylcarbamate, 2-acetylaminobenzimidazole, 2- benzoylaminobenzimidazole, 2-(3,5-dibromo-2-hydroxybenzoylamino)benzimidazole, 1-(3,6-dichloro-2-methoxybenzoyl)-2-aminobenzimidazole, 2-(3,5-dichloro-2- hydroxybenzoylamino)benzimidazole, 2-(3,5-dichloro-2-methoxybenzoylamino) benzimidazole, and 1-(3,5,6-trichloro-2-methoxybenzoyl)-2-aminobenzimidazole. The synthesized compounds have been tested for fungicide activity.