Design and synthesis of abietic acid derivatives containing sulfonamide structure, biological activity and mechanism of action studies

Abstract

Through active splicing techniques and chemical synthesis methods, we have successfully synthesized a series of novel abietic acid derivatives that combine abietic acid backbone with a sulfonamide group. In vitro tests, these derivatives exhibited remarkable antibacterial activities, especially compound C3. Using three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis, we found that the introduction of electron-absorbing groups at the R¹ position, as well as the introduction of larger groups at the R² position, may enhance the antibacterial activity of the target compounds. In addition, studies on the antibacterial mechanism of action of compound C3 showed that it could increase the permeability of bacterial membranes, disrupt the cell membrane of Xanthomonas oryzae pv. oryzicola (Xoc), and effectively inhibit bacterial growth. These findings not only elucidate the antibacterial mechanism of C3, but also provide an important scientific basis for the design and development of new antibacterial agents.