Abstract 2130: Antitumor activity of marin natural product derived Psammaplin A analogs in human lung cancer cells

Abstract

Abstract Natural products are important sources for bioactive molecules, which have been developed to treat various human health-related symptoms. In our continuos efforts to search for anticancer agents from natural sources, Psammaplin A (PsA), isolated from marine natural products, was found to be a potential candidate in the growth inhibition of cancer cells. PsA, a unique symmetrical bromotyrosine contained in a number of marine sponges of the order Verongida, has exhibited a variety of bioactivities including antimicrobial activity, cytotoxicity against the leukemia cell line, and inhibitory activity of DNA gyrase and DNA topoisomerase. PsA is also known to be a potent inhibitor of DNA methyltransferase and histone deacetylase with growth-inhibitory activity of cancer cells. However, its underlying mechanism of action and the structure-activity relationship (SAR) with PsA analogs have not been elucidated yet. In the present study, twenty-eight synthetic analogs of PsA were newly synthesized and examined the potential of cytotoxicities against cancer cells. A SAR study revealed that the presence of free oxime and disulfide functional groups was responsible for high cytotoxicity. Furthermore, the bromotyrosine component in PsA was relatively tolerable and hydrophobic aromatic groups preserved the cytotoxicity. The aromatic groups were dependent on their size and spatial geometry. Among them, a β-naphthyl derivative of PsA showed a potential cytotoxicity and was comparable to that of PsA. The compound also exhibited a potential antitumor activity in a nude mouse xenograft model. These findings indicated that free oxime and disulfide linker in the chemical structure play an important role for cytotoxicity and PsA analogs might be provided as potential antitumor agents. This work was supported by the National Reseach Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (NRF-2016M3A9B6903499) and also supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MEST) (No.2009-0083533). Citation Format: Woong sub Byun, Yoonho Shin, Sang Kook Lee, Hyeung-geun Park, Suckchang Hong. Antitumor activity of marin natural product derived Psammaplin A analogs in human lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2130. doi:10.1158/1538-7445.AM2017-2130