1. One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities.
- Author
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Sun Y, Liu J, Jiang X, Sun T, Liu L, Zhang X, Ding S, Li J, Zhuang Y, Wang Y, and Wang R
- Subjects
- Analgesics therapeutic use, Analgesics toxicity, Animals, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Anti-Inflammatory Agents, Non-Steroidal toxicity, Carrageenan toxicity, Cell Survival drug effects, Cells, Cultured, Cyclooxygenase 1 chemistry, Cyclooxygenase 1 metabolism, Cyclooxygenase 2 chemistry, Cyclooxygenase 2 metabolism, Indoles therapeutic use, Indoles toxicity, Inflammation chemically induced, Inflammation drug therapy, Macrophages cytology, Macrophages metabolism, Mice, Mice, Inbred C57BL, Oxindoles, Pain chemically induced, Pain drug therapy, Rats, Rats, Wistar, Stereoisomerism, Structure-Activity Relationship, Analgesics chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Indoles chemistry
- Abstract
Here we report a facile approach to synthesize highly optically active oxindole-type analogues with both high yield and enantioselectivity. This single-step synthesis strategy represents a substantial improvement upon existing methods that are often involved with multi-step routes and have suboptimal atomic economy. One such compound, namely Q4c, showed remarkable in vivo anti-inflammatory activity with efficiency approaching to that of a steroidal compound dexamethasone. Moreover, Q4c alleviated pain in mouse models with comparable activity to morphine. Further investigation suggested that nitric oxide signaling pathway is involved in the anti-inflammatory and analgesic activities of Q4c. Notably, this is the first time that chiral oxindole-type analogues have been identified to be both anti-inflammatory and analgesic, and our study also paved the way for future development of oxindoles as drug candidates in this field.
- Published
- 2015
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