title: D-amino acids boost the selectivity and confer supramolecular hydrogels of a nonsteroidal anti-inflammatory drug (NSAID).
abstract: As systemically used therapeutics for treating acute or chronic pains or inflammations, nonsteroidal anti-inflammatory drugs (NSAIDs) also associate with the adverse gastrointestinal and renal effects and cardiovascular risks. Thus, it is beneficial to develop topical gels that selectively inhibit cyclooxygenase-2 (COX-2) for the management of local inflammation. In this work, we demonstrate that the covalent conjugation of d-amino acids to naproxen (i.e., a NSAID) not only affords supramolecular hydrogelators for the topical gels but also unexpectedly and significantly elevates the selectivity toward COX-2 about 20× at little expense of the activity of naproxen. This work illustrates a previously unexplored approach that employs d-amino acids for the development of functional molecules that have dual or multiple roles and exceptional biostability, which offers a new class of molecular hydrogels of therapeutic agents.
authors.affiliation: Department of Chemistry, Brandeis University, 415 South St., Waltham, Massachusetts 02454, USA.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xuewen
authors.initials: X
authors.lastname: Du
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009288:Naproxen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D020100:Hydrogels; D009288:Naproxen; D051546:Cyclooxygenase 2