Background: Several clinically used COX-1 and COX-2 inhibitor drugs were reported to possess severe side effects like GI ulcers and cardiovascular disturbances, respectively. Natural products being structurally diverse always attracted the attention of chemists/ medicinal chemists as a potential source of lead molecules in the drug discovery process. COX-2 inhibitory natural products also possess potential cancer chemopreventive property against various cancers including that of colon, breast and prostate.

Methods: Various in vitro, in vivo and in silico standardized methods were used to evaluate COX inhibition property of different secondary metabolites isolated from plant, microbial and marine origin.

Results: We had earlier reported a detailed account of natural product inhibitors of COX reported during 1995-2005, in 2006. In the proposed review, we report 158 natural product inhibitors of COX during 2006 to 2019 belonging to various secondary metabolite classes such as alkaloids, terpenoids, polyphenols as flavonoids, chromones, coumarins, lignans, anthraquinones, naphthalenes, curcuminoids, diarylheptanoids and miscellaneous compounds of plant and marine origin. Further Structure Activity Relationship (SAR) studies of possible leads are also included in the article.

Conclusion: COX inhibitors served as a potential source of lead molecules for the discovery and development of anti-inflammatory drugs. Compilation of natural product and semisynthetic inhibitors of COX may serve as valuable information to the researchers who are looking for possible lead molecules from a natural source to conduct further preclinical and clinical studies.

背景：据报道，几种临床使用的 COX-1 和 COX-2 抑制剂药物分别具有严重的副作用，如胃肠道溃疡和心血管疾病。结构多样的天然产物总是引起化学家/药物化学家的注意，作为药物发现过程中先导分子的潜在来源。COX-2 抑制性天然产物还具有针对各种癌症（包括结肠癌、乳腺癌和前列腺癌）的潜在癌症化学预防特性。

方法：使用各种体外、体内和计算机标准化方法来评估从植物、微生物和海洋来源中分离的不同次级代谢物的 COX 抑制特性。

结果：我们之前曾详细报告了 1995-2005 年和 2006 年报告的 COX 天然产物抑制剂。在拟议的审查中，我们报告了 2006 年至 2019 年期间的 158 种 COX 天然产物抑制剂，属于各种次级代谢物类别，例如生物碱、萜类、多酚类黄酮、色酮、香豆素、木脂素、蒽醌、萘、姜黄素、二芳基庚烷以及植物和海洋来源的杂项化合物。本文还包括对可能线索的进一步结构活性关系 (SAR) 研究。

结论：COX 抑制剂是发现和开发抗炎药物的潜在先导分子来源。COX 的天然产物和半合成抑制剂的汇编可能为正在从天然来源寻找可能的先导分子以进行进一步临床前和临床研究的研究人员提供有价值的信息。