Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
J Nat Prod. 2024 Jun 28;87(6):1601-1610. doi: 10.1021/acs.jnatprod.4c00242. Epub 2024 Jun 4.
Kavaratamide A (), a new linear lipodepsipeptide possessing an unusual isopropyl--methylpyrrolinone moiety, was discovered from the tropical marine filamentous cyanobacterium collected from Kavaratti, India. A comparative chemogeographic analysis of . collected from six different geographical regions led to the prioritized isolation of this metabolite from India as distinctive among our data sets. AI-based structure annotation tools, including SMART 2.1 and DeepSAT, accelerated the structure elucidation by providing useful structural clues, and the full planar structure was elucidated based on comprehensive HRMS, MS/MS fragmentation, and NMR data interpretation. Subsequently, the absolute configuration of was determined using advanced Marfey's analysis, modified Mosher's ester derivatization, and chiral-phase HPLC. The structures of kavaratamides B () and C () are proposed based on a detailed analysis of their MS/MS fragmentations. The biological activity of kavaratamide A was also investigated and found to show moderate cytotoxicity to the D283-medullablastoma cell line.
卡瓦拉肽 A（）是一种新的线性脂肽，具有不寻常的异丙基-甲基吡咯烷酮部分，是从印度卡瓦拉蒂采集的热带海洋丝状蓝细菌中发现的。对从六个不同地理区域采集的进行比较化学生态地理分析，导致优先从印度分离出这种代谢物，这在我们的数据集之间是独特的。基于人工智能的结构注释工具，包括 SMART 2.1 和 DeepSAT，通过提供有用的结构线索加速了结构阐明，并且基于全面的高分辨质谱、MS/MS 碎片和 NMR 数据解释，阐明了完整的平面结构。随后，使用先进的 Marfey 分析、改进的 Mosher 酯衍生化和手性相 HPLC 确定了的绝对构型。根据对其 MS/MS 碎片的详细分析，提出了卡瓦拉肽 B（）和 C（）的结构。还研究了卡瓦拉肽 A 的生物活性，发现它对 D283 髓母细胞瘤细胞系表现出中等的细胞毒性。
