7-Hydroxyneolamellarin A (7-OH-Neo A, 1), a natural marine product derived from sponge Dendrilla nigra, was first synthesized with 10% overall yield under the instruction of convergent synthetic strategy. We found that 7-OH-Neo A could attenuate the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein and inhibit vascular epidermal growth factor (VEGF) transcriptional activity, showing well inhibitory effect on HIF-1 signaling pathway. Meantime, 7-OH-Neo A had the well anti-tumor activities, such as inhibiting tumor angiogenesis, proliferation, migration and invasion. More importantly, 7-OH-Neo A exhibited profound anti-tumor effect in mice breast cancer model by suppressing the accumulation of HIF-1α in tumor tissue. Mechanism study demonstrated that 7-OH-Neo A might target the protein with the ability of stabilizing HIF-1α in hypoxia. Due to the excellent water solubility, superior anti-tumor activity and good biocompatibility, 7-OH-Neo A shows the promising potential for being exploited as an anti-tumor agent in near future.

7-Hydroxyneolamellarin A (7-OH-Neo A, 1 )，一种源自海绵Dendrillilla nigra的天然海产品，首先在收敛合成策略的指导下以 10% 的总产率合成。我们发现7-OH-Neo A可以减弱缺氧诱导因子-1α（HIF-1α）蛋白的积累，抑制血管表皮生长因子（VEGF）的转录活性，对HIF-1信号通路有很好的抑制作用。同时，7-OH-Neo A具有良好的抗肿瘤活性，如抑制肿瘤血管生成、增殖、迁移和侵袭。更重要的是，7-OH-Neo A 通过抑制 HIF-1α 在肿瘤组织中的积累，在小鼠乳腺癌模型中表现出显着的抗肿瘤作用。机理研究表明，7-OH-Neo A可能靶向具有在缺氧条件下稳定HIF-1α的能力的蛋白质。由于优异的水溶性、优越的抗肿瘤活性和良好的生物相容性，