Quinoline, a well-known heterocyclic compound, itself has few applications; however, many of its derivatives are useful in diverse therapeutic applications, such as antimalarials (Quinine and Quinidine), antiviral (Saquinavir) and anticancer (Camptothecin, Irinotecan and Topotecan). Over the past decades, the syntheses and the biological activities of quinoline-5,8-diones have been reported. In addition, various functionalized quinoline-5,8-dione moieties are present in many classes of biologically active compounds, such as antitumor agents lavendamycim, streptonigrin and styrylquinoline derivatives with perspective HIV integrase inhibitors. In the course of screening for bioactive metabolite from microbial sources, a strain Saccharopolyspora sp. YIM M13568 isolated from the mangrove rhizosphere was selected for (1) its excellent cytotoxic activity; (2) kinds of compounds with MWs in the range of 200 − 300 amu possessing the UV chromophores at ~ 350, 300, 260 and 220 nm. In this study, we reported fermentation, isolation and structural elucidation of four quinoline alkaloids (1–4) and a new naphthalene derivative (5) from Saccharopolyspora sp. YIM M13568, and their cytotoxic activities.