Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening

Moaz M Abdou; Ferenc Ötvös; Dewen Dong; Magdalini Matziari

doi:10.1186/s13065-023-01075-1

Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening

BMC Chem. 2023 Nov 25;17(1):167. doi: 10.1186/s13065-023-01075-1.

Authors

Moaz M Abdou¹, Ferenc Ötvös², Dewen Dong³, Magdalini Matziari⁴

Affiliations

¹ Egyptian Petroleum Research Institute, P.O. 11727, Nasr City, Cairo, Egypt. moaz.chem@gmail.com.
² Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, 6726, Szeged, Hungary.
³ Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
⁴ Department of Chemistry, Xi'an Jiaotong Liverpool University, Suzhou, 215123, Jiangsu, People's Republic of China.

Abstract

Like most phosphinic acids, the potent and selective RXP03 inhibitor of different MMPs exhibited moderate absorption and low bioavailability, which impaired its use. In an unprecedented attempt, we present an interesting synthetic approach to a new class of phosphinate prodrug, glycosyl ester of RXP03, to provide a potentially improved blood-brain barrier (BBB) behavior compared to the former lead compound RXP03. To validate this speculation, a predictive study for permeability enhancer of glycosyl ester of RXP03 showed encouraging insights to improve drug delivery across biological barriers.

Keywords: Matrix metalloproteases; Molecular docking; Permeability enhancer; Phosphinic ester; Prodrug; RXP03.