Matches in SemOpenAlex for { <https://semopenalex.org/work/W2808583595> ?p ?o ?g. }
- W2808583595 endingPage "3110" @default.
- W2808583595 startingPage "3101" @default.
- W2808583595 abstract "Aceclofenac is a popular analgesic, antipyretic, and nonsteroidal anti-inflammatory drug (NSAID) used for prolonged treatment (at least three months) in musculoskeletal disorders. It is characterized by several limitations such as poor water solubility and low oral bioavailability. The main side-effect of aceclofenac, as well as all NSAIDs, is the gastrotoxicity; among other adverse effects, there is the risk of bleeding since aceclofenac reversibly inhibits platelet aggregation. With the aim to reduce these drawbacks, we have designed, synthesized, and characterized, both in vitro and in vivo, an orally administrable pro-drug of aceclofenac (ACEgal). ACEgal was obtained by conjugating carboxyl group with the 6-OH group of d-galactose; its structure was confirmed by X-ray powder diffractometry. The pro-drug was shown to be stable at 37 °C in simulated gastric fluid (SGF-without pepsin, pH = 1.2) and moderately stable in phosphate buffered saline (PBS, pH = 7.4). However, it hydrolyzed in human serum with a half-life (t1/2) of 36 min, producing aceclofenac. Furthermore, if compared to its parent drug, ACEgal was four-times more soluble in SGF. To predict human intestinal absorption, cell permeability in a Caco-2 model of aceclofenac and ACEgal was determined. Anti-inflammatory, analgesic, and ulcerogenic activities have been investigated in vivo. In addition, oxidative stress parameters (thiobarbituric acid reactive substances, TBARS, and glutathione, GSH) and platelet antiaggregatory activity both of parent drug and pro-drug were evaluated. Results clearly showed that the conjugation of aceclofenac to a galactose molecule improves physicochemical, toxicological (at gastric and blood level), and pharmacological profile of aceclofenac itself without changing intestinal permeability and antiplatelet activity (in spite the new sugar moiety)." @default.
- W2808583595 created "2018-06-21" @default.
- W2808583595 creator A5006463761 @default.
- W2808583595 creator A5009764916 @default.
- W2808583595 creator A5014999187 @default.
- W2808583595 creator A5018783066 @default.
- W2808583595 creator A5023802122 @default.
- W2808583595 creator A5033561040 @default.
- W2808583595 creator A5034913038 @default.
- W2808583595 creator A5037074434 @default.
- W2808583595 creator A5037128615 @default.
- W2808583595 creator A5037203019 @default.
- W2808583595 creator A5038305581 @default.
- W2808583595 creator A5046495200 @default.
- W2808583595 creator A5047107350 @default.
- W2808583595 creator A5060565595 @default.
- W2808583595 creator A5064457717 @default.
- W2808583595 creator A5088678144 @default.
- W2808583595 date "2018-06-18" @default.
- W2808583595 modified "2023-10-14" @default.
- W2808583595 title "Aceclofenac–Galactose Conjugate: Design, Synthesis, Characterization, and Pharmacological and Toxicological Evaluations" @default.
- W2808583595 cites W1573637659 @default.
- W2808583595 cites W1964673951 @default.
- W2808583595 cites W1965397793 @default.
- W2808583595 cites W1972832497 @default.
- W2808583595 cites W1975292875 @default.
- W2808583595 cites W1979196526 @default.
- W2808583595 cites W1984810484 @default.
- W2808583595 cites W1985703032 @default.
- W2808583595 cites W1986606898 @default.
- W2808583595 cites W1988661248 @default.
- W2808583595 cites W2002762671 @default.
- W2808583595 cites W2002924275 @default.
- W2808583595 cites W2004848791 @default.
- W2808583595 cites W2007567412 @default.
- W2808583595 cites W2013265415 @default.
- W2808583595 cites W2016415795 @default.
- W2808583595 cites W2023316127 @default.
- W2808583595 cites W2031757346 @default.
- W2808583595 cites W2037759437 @default.
- W2808583595 cites W2038917994 @default.
- W2808583595 cites W2041802266 @default.
- W2808583595 cites W2042401508 @default.
- W2808583595 cites W2043824503 @default.
- W2808583595 cites W2047734086 @default.
- W2808583595 cites W2049908664 @default.
- W2808583595 cites W2055565705 @default.
- W2808583595 cites W2056225153 @default.
- W2808583595 cites W2066646706 @default.
- W2808583595 cites W2068120128 @default.
- W2808583595 cites W2075011939 @default.
- W2808583595 cites W2075050741 @default.
- W2808583595 cites W2076023317 @default.
- W2808583595 cites W2082064600 @default.
- W2808583595 cites W2100179443 @default.
- W2808583595 cites W2100568225 @default.
- W2808583595 cites W2106755454 @default.
- W2808583595 cites W2107163131 @default.
- W2808583595 cites W2108879539 @default.
- W2808583595 cites W2118326273 @default.
- W2808583595 cites W2136948883 @default.
- W2808583595 cites W2138698403 @default.
- W2808583595 cites W2142158566 @default.
- W2808583595 cites W2154331382 @default.
- W2808583595 cites W2170745987 @default.
- W2808583595 cites W2227754270 @default.
- W2808583595 cites W2282362572 @default.
- W2808583595 cites W2299605484 @default.
- W2808583595 cites W2315533978 @default.
- W2808583595 cites W2408765840 @default.
- W2808583595 cites W2412057056 @default.
- W2808583595 cites W2586274104 @default.
- W2808583595 cites W2761166271 @default.
- W2808583595 cites W2767536906 @default.
- W2808583595 cites W2768155517 @default.
- W2808583595 cites W4229948187 @default.
- W2808583595 doi "https://doi.org/10.1021/acs.molpharmaceut.8b00195" @default.
- W2808583595 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29912563" @default.
- W2808583595 hasPublicationYear "2018" @default.
- W2808583595 type Work @default.
- W2808583595 sameAs 2808583595 @default.
- W2808583595 citedByCount "9" @default.
- W2808583595 countsByYear W28085835952019 @default.
- W2808583595 countsByYear W28085835952020 @default.
- W2808583595 countsByYear W28085835952021 @default.
- W2808583595 countsByYear W28085835952022 @default.
- W2808583595 countsByYear W28085835952023 @default.
- W2808583595 crossrefType "journal-article" @default.
- W2808583595 hasAuthorship W2808583595A5006463761 @default.
- W2808583595 hasAuthorship W2808583595A5009764916 @default.
- W2808583595 hasAuthorship W2808583595A5014999187 @default.
- W2808583595 hasAuthorship W2808583595A5018783066 @default.
- W2808583595 hasAuthorship W2808583595A5023802122 @default.
- W2808583595 hasAuthorship W2808583595A5033561040 @default.
- W2808583595 hasAuthorship W2808583595A5034913038 @default.
- W2808583595 hasAuthorship W2808583595A5037074434 @default.
- W2808583595 hasAuthorship W2808583595A5037128615 @default.
- W2808583595 hasAuthorship W2808583595A5037203019 @default.