Biocatalytic synthesis of β-carboline analogues with anti-myocardial fibrosis effect using the amide bond synthetase MarA

Abstract

The β-carboline scaffold and amide bond have great potential for drug discovery as consisting in many marketed pharmaceuticals and drug candidates. Compared to the chemical method, enzymatic synthesis of amide with nontoxicity and mild reaction conditions has received great attention. In this study, the amide bond synthetase MarA was characterized, and a series of novel amide-containing β-carboline analogues were synthesized by MarA-catalyst. Compound 5b having fluorine substitution, and compound 5n possessing an N-methyl substituent, showed excellent anti-myocardial fibrosis effects, which were found to be superior to the positive control drug, captopril. Our study provides MarA as a new green biocatalytic strategy for the synthesis of new β-carboline analogues with anti-fibrotic properties.