Synthesis and biological evaluation of Argemone mexicana -inspired antimicrobials

• Published in: Beilstein journal of organic chemistry 2023-09, Vol.19 (1), p.1511-1524
• Main Authors: Villegas, Jessica, Ball, Bryce C, Shouse, Katelyn M, VanArragon, Caleb W, Wasserman, Ashley N, Bhakta, Hannah E, Oliver, Allen G, Orozco-Nunnelly, Danielle A, Pruet, Jeffrey M
• Format: Article
• Language: English
• Subjects: benzylisoquinoline; berberine; chelerythrine; Chemistry; drug discovery; Full Research Paper; plant-derived antimicrobials
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.19.108

Due to the lack of new antimicrobial drug discovery in recent years and an ever-growing prevalence of multidrug-resistant “superbugs”, there is a pressing need to explore alternative ways to combat pathogenic bacterial and fungal infections. Building upon our previous work in the field of medicinal phytochemistry, the present study is focused on designing, synthesizing, and testing the altered bioactivity of new variants of two original bioactive molecules found in the Argemone mexicana plant. Herein, we report upon 14 variants of berberine and four variants of chelerythrine that have been screened against a pool of 12 microorganisms (five Gram-positive and four Gram-negative bacteria, and three fungi). Additionally, the crystal structures of two berberine variants are described. Several berberine variants show enhanced antibacterial activity compared to the unaltered plant-derived molecule. We also report promising preliminary tumor cytotoxicity effects for a number of the berberine derivatives.