Green synthesis of diethyl((2-iodo-4-(trifluoromethyl)phenyl)amino)(aryl)methyl)phosphonates as potent α-glucosidase inhibitors

Abstract

Novel diethyl((2-iodo-4-(trifluoromethyl)phenyl)amino)(aryl)methyl)phosphonates (4a-j) were synthesized via a simple and efficient one pot by three-component condensation reaction (Kabachnik-Fields reaction) of 2-iodo-4-trifluoromethyl aniline, aromatic aldehydes and diethyl phosphite in presence of anatase TiO₂ nanoparticles as catalyst under solvent free conditions. The molecular docking studies of synthesized compounds with α-glucosidase enzyme revealed that these compounds have strong α-glucosidase inhibitory activity. The synthesized compounds (4a-j) are also screened for in vitro α-glucosidase inhibitory activity and the results showed compound 4i as the strongest inhibitor and compounds 4a, 4b, 4f and 4g as stronger inhibitors even better than the reference standard acarbose.

Graphical Abstract

Keywords:

• Acarbose
• anatase TiO₂ nanoparticles
• α-glucosidase inhibitory activity
• Kabachnik-fields reaction
• molecular docking

Acknowledgements

The authors express thanks to Prof. C. Devendranath Reddy, Department of Chemistry, Sri Venkateswara University, Tirupati, for his helpful discussions and University Grants Commission (UGC), New Delhi for funding and providing fellowship (BSR-RFSMS) to Mr. Shaik Mahammad Sadik. One of the authors Mr. Mohan Gundluru acknowledges DST-PURSE 2nd hase Program in S.V. University, Tirupati funded by DST New Delhi, India for providing instrumentation facility and funding through SRF (File No: 17118-UGC-III(3)/DST-PURSE 2nd Phase/2017, Dt: 23-08-2018).