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A new marine-derived macrolide designated as neopeltolide (1) has been isolated from a deep-water sponge of the family Neopeltidae. Its structure was elucidated on the basis of spectroscopic data interpretation. Neopeltolide (1) is a potent inhibitor of the in vitro proliferation of the A-549 human lung adenocarcinoma, the NCI-ADR-RES human ovarian sarcoma, and the P388 murine leukemia cell lines, with IC₅₀'s of 1.2, 5.1, and 0.56 nM, respectively. Neopeltolide (1) also inhibited the growth of the fungal pathogen Candida albicans with a minimum inhibitory concentration of 0.62 μg/mL.