Six serinal derivatives were synthesized and tested for their anti-human immunodeficiency virus type-1 (HIV-1) activity against HIV-1-infected cells. Of the 6 serinal derivatives tested, only N,O-didecanoyl serinal dimethylacetal (DDSD) was found to strongly suppress progeny virus production from acute HIV-1-infected CEM cells, while not suppressing the HIV-1 p24 production from latent HIV-1-infected ACH-2 cells after stimulation with phorbol 12-myristate 13-acetate. DDSD also inhibited the synthesis of HIV-1 proviral DNA at 20-50 microM, not only 1 h but also 24 h after HIV-1 infection. Taken together, DDSD is a potent inhibitor of HIV-1 production, and may become a unique leading compound for chemotherapy of acquired immunodeficiency syndrome.