Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Chemistry, National Forensic Sciences University Delhi Campus, New Delhi 110085, India.
Molecules. 2022 Oct 14;27(20):6905. doi: 10.3390/molecules27206905.
The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.
4-丙烯基愈创木酚是一种天然酚类分子，因其具有抗氧化能力，可对抗活性氧介导的细胞损伤，因此被广泛研究。因此，我们假设同时使用抗氧化剂和非甾体抗炎药可能会降低胃肠道毒性的风险，使治疗更安全。为了解决传统非甾体抗炎药的胃肠道毒性问题，我们通过计算开发、化学合成并测试了一种新的 S-萘普生-4-丙烯基愈创木酚杂合体（MAS-1696）的抗炎效果和胃肠道安全性。MAS-1696 对环氧化酶-2（COX2）、15-脂氧合酶-2（15-LOX2）和脂氧合酶-5（5-LOX）的体外抑制能力表明，其对 COX2 的抑制作用更强。此外，与母体化合物萘普生相比，MAS-1696 杂合体的 COX 选择性指数提高了 23%，这意味着其疗效更高，胃安全性也更高。体内数据表明，MAS-1696 引起胃肠道损伤的可能性小于萘普生，同时发挥抗炎和镇痛作用与萘普生相当或优于萘普生。总之，MAS-1696 具有口服活性、生物可变性和结晶性，使其成为一种可口服给药的药物。
