Abstract

A green and efficient one-pot has been developed for the synthesis of a series of new diethyl-(((2,3-dihydrobenzo[b][1, 4] dioxin-6yl)amino)(substituted phenyl)methyl) phosphonates (4a-k) by the Kabachinik-Fields reaction of 2,3-dihydrobenzo[b] [1, 4]dioxin-6-amine (1) with various substituted aldehydes (2a-k) and diethyl phosphite (3) using nano ferrite supported glutathione (nano FGT) as catalyst under microwave irradiation and solvent free conditions. The synthesized compounds were evaluated for their antioxidant (DPPH & FRAP) and anti-inflammatory activity studies. Compounds 4b (naphthyl) and 4k (9-anthracenyl) showed highest antioxidant activity than that of standard ascorbic acid in DPPH method. Whereas compounds 4f (3-nitrophenyl), 4h (3-phenoxyphenyl) and 4k (9-anthracenyl) exhibited low IC₅₀ values than that of standard ascorbic acid in and in Ferric Reducing Antioxidant Power (FRAP) studies. Compounds 4a, 4b, 4h, 4i, and 4k have shown strong anti-inflammatory activity against LPS induced cell death in RAW 264.7 cell lines. Molecular docking studies were also carried out against COX-2 showed high binding energies that are in support of their high anti-inflammatory activity. Being the most bioactive compound (4k) stands as promising next future anti-oxidant and anti-inflammatory agent.

摘要

开发了一种绿色高效的一锅法合成一系列新型二乙基-(((2,3-dihydrobenzo[b][1, 4] dioxin-6yl)amino)(取代的苯基)甲基)膦酸酯(图 4a-k ) 通过 2,3-二氢苯并[b] [1, 4]dioxin-6-amine ( 1 ) 与各种取代的醛 ( 2a-k ) 和亚磷酸二乙酯 ( 3 ) 使用纳米铁氧体进行 Kabachinik-Fields 反应在微波辐射和无溶剂条件下负载型谷胱甘肽（纳米 FGT）作为催化剂。对合成的化合物进行了抗氧化（DPPH 和 FRAP）和抗炎活性研究的评估。化合物4b（萘基）和4k(9-蒽)在DPPH法中显示出比标准抗坏血酸最高的抗氧化活性。而化合物4f (3-硝基苯基)、4h (3-苯氧基苯基) 和4k (9-蒽基)在铁还原抗氧化能力 (FRAP) 研究中表现出比标准抗坏血酸低的 IC _50值。化合物4a、4b、4h、4i和4k在 RAW 264.7 细胞系中显示出对 LPS 诱导的细胞死亡的强烈抗炎活性。还针对 COX-2 进行的分子对接研究显示了高结合能，这支持了它们的高抗炎活性。作为最具生物活性的化合物 ( 4k )，有望成为未来的抗氧化剂和抗炎剂。