Design and synthesis of furoxan-based nitric oxide-releasing glucocorticoid derivatives with potent anti-inflammatory activity and improved safety.
A series of furoxan-based nitric oxide-releasing glucocorticoid derivatives was synthesized. The pharmacological assays indicated that three compounds, including I(4), I(5), and I(6), had anti-inflammatory activity. Furthermore compared with the leading compound hydrocortisone the safety of I(6) was greatly improved. Due to releasing NO in vivo the side effects of glucocorticoids, including hypertension and osteoporosis, were effectively avoided.
Fang
Lei
L
Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Zhang
Yihua
Y
Lehmann
Jochen
J
Wang
You
Y
Ji
Hui
H
Ding
Dayong
D
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002351:Carrageenan; D049109:Cell Proliferation / Q000187:drug effects; D032561:Cotton Fiber; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005938:Glucocorticoids / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010069:Oxadiazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014992:Xylenes
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D010069:Oxadiazoles; D014992:Xylenes; C010166:furoxans; D009569:Nitric Oxide; D002351:Carrageenan; D000469:Alkaline Phosphatase