Synthesis, molecular docking, and in vitro activity of a novel angiotensin-converting enzyme 2 inhibitor, LMS1007: a potential molecule in Covid-19 and cancer treatments

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a validated commonly studied in the pathology of several diseases, including novel coronavirus and breast cancer. Herein, we report the synthesis, molecular docking, and validation of a novel ACE2 inhibitor that was previously discovered by our team based on diverse scaffolds of other ACE2 inhibitors and carnosine. The synthesized 4-subsitituted imidazole compound, namely, LMS1007, was characterized through ¹H-NMR, LC-MS, and SFC. LMS1007 was then tested in vitro with ACE2 and viral spike protein–ACE2 inhibitor kits and was found to be approximately 100 times more potent as an ACE2 inhibitor than carnosine. However, it was less potent than the standard ACE2 inhibitor. In the same concentration range of the standard drug for ACE2 inhibition, LMS1007 demonstrated similar inhibitory effects on the interaction of the viral spike protein with ACE2. LMS1007 had an inhibitory concentration of 50% (IC₅₀) at a concentration of 2.3 mM in all kits. LMS1007, similar to carnosine in breast cancer cell lines, exhibited potential inhibitory effects on the ACE2-mediated host uptake of Covid-19. Thus, a thorough review and discussion are provided on the role of ACE2 as an attractive target for the development of new drugs for Covid-19 treatment.