<jats:title>Abstract</jats:title><jats:p>Four new antimycin alkaloids (<jats:bold>1</jats:bold>–<jats:bold>4</jats:bold>) and six related known analogs (<jats:bold>5</jats:bold>–<jats:bold>10</jats:bold>) were isolated from the culture of a marine derived<jats:italic>Streptomyces</jats:italic>sp. THS-55, and their structures were elucidated by extensive spectroscopic analysis. All of the compounds exhibited potent cytotoxicity<jats:italic>in vitro</jats:italic>against HPV-transformed HeLa cell line. Among them, compounds<jats:bold>6</jats:bold>–<jats:bold>7</jats:bold>were derived as natural products for the first time, and compound<jats:bold>5</jats:bold>(NADA) showed the highest potency. NADA inhibited the proliferation, arrested cell cycle distribution, and triggered apoptosis in HeLa cancer cells. Our molecular mechanic studies revealed NADA degraded the levels of E6/E7 oncoproteins through ROS-mediated ubiquitin-dependent proteasome system activation. This is the first report that demonstrates antimycin alkaloids analogue induces the degradation of high-risk HPV E6/E7 oncoproteins and finally induces apoptosis in cervical cancer cells. The present work suggested that these analogues could serve as lead compounds for the development of HPV-infected cervical cancer therapeutic agents, as well as research tools for the study of E6/E7 functions.