Bioassay-guided fractionation of a cytotoxic EtOAc extract of the endophytic fungus Streptomyces albofaciens occurring in the leaf tissue of Agave parryi afforded two new natural products, cyclo (Tyr-Tryp) (1) and iso-streptimidone (2), and the known compounds, streptimidone (3), dealanylascamycin (4), and phenethylamide (5). The structures of 1 and 2 were elucidated by spectroscopic methods including 2D NMR. All compounds were evaluated for cytotoxicity in a panel of four human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast), SF-268 (CNS glioma), MIA Pa Ca-2 (pancreatic carcinoma)] and normal human fibroblast cells (WI-38), and only 2 - 4 were found to be active. Dealanylascamycin (4) was highly active (IC50 = 0.02-1.01 µM) and was selective against all four cancer cell lines; its activity was found to be 30 to 50 times greater in cancer cell lines compared to the normal human fibroblast cells.