Abdou Moaz M, Ötvös Ferenc, Dong Dewen, Matziari Magdalini
Egyptian Petroleum Research Institute, P.O. 11727, Nasr City, Cairo, Egypt.
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, 6726, Szeged, Hungary.
BMC Chem. 2023 Nov 25;17(1):167. doi: 10.1186/s13065-023-01075-1.
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.
与大多数次膦酸一样，不同基质金属蛋白酶（MMPs）的强效选择性RXP03抑制剂表现出中等吸收和低生物利用度，这限制了其应用。在一次前所未有的尝试中，我们提出了一种有趣的合成方法，用于合成一类新型次膦酸酯前药，即RXP03的糖基酯，与之前的先导化合物RXP03相比，有望改善血脑屏障（BBB）性能。为了验证这一推测，对RXP03糖基酯的通透性增强剂进行的预测性研究显示了令人鼓舞的结果，有助于改善药物跨生物屏障的递送。
