A search for HIV-1 integrase (IN) inhibitors from natural sources has led to the isolation of compounds from Dioscorea bulbifera bulbils. From the bioassay-guided isolation, the chloroform fraction was then fractionated to obtain one new clerodane diterpenoid (diosbulbin E acetate, 4), two known clerodane diterpenoids (1-2), four flavonoids (5-8) and one sterol glucoside (3). Quercetin (7) exhibited the strongest anti-HIV-1 IN activity with an IC50 value of 16.28 µM, followed by kaempferol (8, IC50 = 37.71 µM), whereas (+)-catechin (6) possessed moderate activity (IC50 = 62.36 µM). Moreover, the clerodane-type diterpenoids (1 and 4) also exhibited moderate inhibitory effects with IC50 values of 70.39 and 73.49 µM, respectively. The flavonoid compounds (5-8) were also investigated for their interactions with the IN active sites using a molecular docking method. They interacted with Thr66, His67, Gln148, Glu152 and Lys159, which are important amino acid residues for inhibition of HIV-1 IN activity.
