Bone-targeting glycol and NSAIDS ester prodrugs of rhein: Synthesis, hydroxyapatite affinity, stability, anti-inflammatory, ulcerogenicity index and pharmacokinetics studies

Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors

“…Compounds 7a-7j were treated with oxalyl chloride and condensed with tert-butyl (2-aminophenyl)carbamate in dry THF with N-methylmorpholine as a base to generate 8a-8j [25]. 2-Aminobenzamide compounds 10a-10j were finally obtained by de-protection of 8a-8j with trifluoroacetic acid (TFA) in dichloromethane at room temperature in high yields.…”

Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs

“…Paw edema was induced, 5 min later, by subplantar injection of 0.1 mL of sterile saline containing 1% λ-carrageenan into the hind paw. At predetermined intervals (2,4,6,8,24,48,72, and 96 h following injection), paw edema and mechanical hyperalgesia were evaluated (n = 6). Paw volumes were measured by a plethysmometer (Ugo Basile, Milan, Italy), and the increase in paw volume was assessed as the difference between the volume measured at each time point and the basal volume measured before carrageenan injection.…”

“…Drug delivery was pursued using Hill Top Chambers with webril pad (19 mm, Hill Top research, St. Petersburg, USA) loaded with 0.5 g of hydroalcoholic gel applied on the back of the shaved animal for 2 h (n = 5). At predetermined intervals (2,4,6,24,48,72, and 96 h following patches applications), mice were euthanized by CO 2 , and skin underlying permeation area was excised. Tissue samples were weighted and homogenized in a solution of methanol and a serine protease inhibitor, phenylmethylsulfonyl fluoride (PMSF, 1 mM).…”

Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors

“…Targeting properties of the synthesized BPs at the bone site were investigated directly on hydroxyapatite powder (HAP), in order to predict their possible in vivo interaction. Among the different analytic techniques already described in the literature, such as HPLC [22,26] or NMR [23] determinations, we decided to quantify relative binding affinity of this new set of bisphosphonates to hydroxyapatite through UV spectrophotometry technique. [27] This sensitive method, in fact, easily allows to detect and compare BPs affinity with that of tiludronate as shown in Table 2.…”