Inhibition of the replication of HIV-1 by norcantharidin in vitro

For obtaining new structural compounds with unique resistance profiles or novel mechanisms of action on HIV-1 from natural products, anti-HIV-1 drug screening models were used in vitro.  Norcantharidin (NCTD), a derivative from cantharidin, was found to have inhibitory activities on HIV-1_ⅢB p24 antigen in   lymphocyte lines MT-4, CEM and H9.  It inhibited HIV-1 strain 018a (sensitive to zidovudine) from replicating with EC₅₀ (50% effective concentration) of 14.9 μmol·L⁻¹ and also inhibited HIV-1 strain 018c (resistant to    zidovudine) from replicating with EC₅₀ of 20.2 μmol·L^{−1 in primary lymphocytes peripheral blood mononuclear cells (PBMC)}.  Norcantharidin showed synergistic activity with zidovudine on HIV-1_ⅢB in MT-4 cells, the  combination index was less than 0.3.  But, it was not active on HIV-1 integrase, reverse transcriptase or protease in vitro.  As the structure of norcantharidin is unique and different from that of all clinic drugs approved, it would be possible to obtain new and effective compounds against HIV-1 with low toxicities after modification of norcantharidin.