Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs.

Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs.
Eur J Med Chem. 2020 Apr 09;196:112271
Authors: Wang C, Xi D, Wang H, Niu Y, Liang L, Xu F, Peng Y, Xu P
Abstract
A series of hybrids of MEK inhibitor and nitric oxide donor have been designed and synthesized. Compound 18h [4-(3-((3-(2-fluoro-3-((N-methylsulfamoyl)amino)benzyl)-4-methyl-2-oxo-2H-chromen-7-yl)oxy) propoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide] was proven to be more potent than the clinical compound RO5126766 in MDA-MB-231 cells. Compound 18h can significantly reduce the levels of pMEK and pERK, induce cell apoptosis in MDA-MB-231 cells, and release NO in cells efficiently, suggesting that these hybrids, while displaying the properties of both MEK inhibitors and NO donors have a mechanism of action different from that of MEK inhibitors and NO donors. Thus, we are able to report a series of multitarget hybrids with better antitumor potency than a known MEK inhibitor and NO donor.
PMID: 32305784 [PubMed - as supplied by publisher]

Source: European Journal of Medicinal Chemistry - April 8, 2020 Category: Chemistry Authors: Wang C, Xi D, Wang H, Niu Y, Liang L, Xu F, Peng Y, Xu P Tags: Eur J Med Chem Source Type: research