Publications by authors named "Hashim Javaid"
Article Synopsis
- PARP-2 is a poly(ADP-ribose) polymerase with activities somewhat like PARP-1 but serves distinct purposes; researchers designed and tested selective inhibitors targeting PARP-2 using isoquinolin-1-one compounds.
- A new method was developed to synthesize 5-aminoisoquinolin-1-one, which was then modified through acylation and other chemical processes to create variants for testing.
- Among the tested compounds, 5-benzamidoisoquinolin-1-one showed the highest selectivity for PARP-2, indicating its potential as a valuable inhibitor, with a comparative selectivity ratio significantly favoring PARP-2 over PARP-1.
Article Synopsis
- Researchers are focused on efficiently synthesizing 4,5-disubstituted isoquinolin-1-ones due to the drug potential of 5-aminoisoquinolin-1-one (5-AIQ).
- Protection strategies for brominated derivatives allowed for successful couplings using different techniques, despite challenges with sterics and electronics.
- A new compound, 5-amino-4-(4-trifluoromethylphenyl)isoquinolin-1-one, has been discovered as a potent inhibitor for the enzyme PARP-2.
Poly(ADP-ribose) polymerase activation is an immediate cellular response to metabolic-, chemical-, or ionizing radiation-induced DNA damage and represents a new target for cancer therapy. In this article, we disclose a novel series of substituted 4-benzyl-2 H-phthalazin-1-ones that possess high inhibitory enzyme and cellular potency for both PARP-1 and PARP-2. Optimized compounds from the series also demonstrate good pharmacokinetic profiles, oral bioavailability, and activity in vivo in an SW620 colorectal cancer xenograft model.
View Article and Find Full Text PDFWe have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors.
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