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
Department of Chemistry, Valparaiso University, 1710 Chapel Dr, Valparaiso, IN 46383, USA.
Department of Biology, Valparaiso University, 1610 Campus Dr, Valparaiso, IN 46383, USA.
Beilstein J Org Chem. 2023 Sep 29;19:1511-1524. doi: 10.3762/bjoc.19.108. eCollection 2023.
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 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.
由于近年来缺乏新的抗菌药物研发，且多重耐药“超级细菌”的患病率不断上升，迫切需要探索对抗致病性细菌和真菌感染的替代方法。基于我们之前在药用植物化学领域的工作，本研究专注于设计、合成和测试从该植物中发现的两种原始生物活性分子新变体的生物活性变化。在此，我们报告了针对12种微生物（5种革兰氏阳性菌、4种革兰氏阴性菌和3种真菌）筛选的14种小檗碱变体和4种白屈菜红碱变体。此外，还描述了两种小檗碱变体的晶体结构。与未改变的植物衍生分子相比，几种小檗碱变体显示出增强的抗菌活性。我们还报告了一些小檗碱衍生物有前景的初步肿瘤细胞毒性作用。
