An efficient nano-FGT catalyzed green synthesis of α-aminophosphonates and evaluation of their antioxidant, anti-inflammatory activity and molecular docking studies

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.

Graphical Abstract

Keywords:

• α-Aminophosphonates
• anti-inflammatory activity
• antioxidant activity
• green synthesis
• molecular docking studies

Acknowledgements

The authors also thank Prof. C. Devendranath Reddy (Retd.), Sri Venkateswara University, Tirupati, India, for helpful discussions. One of the author Dr. G Mohan acknowledges DST-PURSE 2nd Phase Programme facilitated at Sri Venkateswara University, Tirupati, India supported by Department of Science and Technology, New Delhi, India [17118-UGC-III(3)/DST-PURSE 2^nd Phase/2017, Dt: 23-08-2018] for instrumental analysis.

Additional information

Funding

One of the authors SHAIK HAROON YASMIN expresses her thanks to the Department of Science and Technology, New Delhi, India for the financial support under DST-INSPIRE Fellowship program No. DST/INSPIRE Fellowship/IF170317, dated: 24/05/2017. One of the author Dr. G Mohan acknowledges DST-PURSE 2nd Phase Programme facilitated at Sri Venkateswara University, Tirupati, India supported by Department of Science and Technology, New Delhi, India [17118-UGC-III(3)/DST-PURSE 2nd Phase/2017, Dt: 23-08-2018] for funding. One of the authors Dr. S. Santhisudha expresses her sincere thanks to DST, New Delhi, India, for providing financial support through Woman Scientist Scheme-A (WOS-A) (F. no.: SR/WOS-A/CS-104/2018, Dated: 14-09-2020).