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The antiprotozoal and antimicrobial properties of the extract and fractions of the whole plant of Pallenis hierochuntica were investigated against a panel of pathogenic organisms. Fractionation of the methanol extract of the whole plant of P. hierochuntica using reverse-phase chromatography gave 28 fractions and led to the isolation of 2 new bisabolone hydroperoxides, 6,10ß,11-trihydroxybisabol-2-ene-1-one (1a), 6,10a,11-trihydroxybisabol-2-ene-1-one (1b) and also 6,10ß-dihydroxybisabol-2,11-diene-1-one (2). They were characterised by extensive spectrometric analysis. Anti-infective investigations of the fractions revealed that fractions 22 to 26 possessed significant antimalarial activity against the D6 and W2 strains of Plasmodium falciparum with IC50 = 7.62-9.91 µg/mL and 5.49-6.08 µg/mL, respectively, and SI > 6.0 on average. Fractions 7, 16 to 24 exhibited good activity against Leishmania donovani promastigotes (IC50 = 6.71-18.77 µg/mL). Fractions 25 to 28 were active against Trypanosoma brucei trypomastigotes, fraction 25 being the most potent (IC50 = 4.13 µg/mL). Only fractions 11 to 13 were active against Aspergillus fumigatus (IC50 = 13.406 µg/mL). Compounds 1a and 2 were not promising against the organisms tested. 1a and 1b were characterised for the first time. [ABSTRACT FROM AUTHOR]

Two humulene derivatives (asteriscunolides A (1) and C (2)) were isolated from the methanolic extract of the whole plant of Asteriscus hierochunticus. Their structures were characterized by IR, 1D, and 2D NMR and HRESIMS data analysis, in addition to comparison with literature. Compounds 1 and 2 exhibited excellent in vitro antileishmanial activities against Leishmania donovani promastigotes with IC50 values of 8.38 and 3.26 µg/mL and against Leishmania donovani axenic amastigotes with IC50 values of 9.41 and 4.69 µg/mL, respectively while Pentamidine (the standard drug) exhibited IC50 values of 4.40 and 29.36, respectively. The isolated compounds possessed good activities against Plasmodium falciparum (D6) and (W2) strains with IC50 values ranging from 3.134 - 4.153 µg/mL. Furthermore, 1 and 2 showed no cytotoxic activity against the transformed human monocytic (THP1) cells. The chemical structures of 1 and 2 showed the essential pharmacophoric features of tubulin inhibitors that act through the colchicine binding site. Accordingly, molecular docking studies against the colchicine binding site of Leishmania tubulin have been preceded. Compounds 1 and 2 showed excellent binding mode with free energies of -5.62 and -5.54 kcal/mol, respectively. Further in silico studies were carried out and expected that 1 and 2 have the likeness to be drugs through exhibiting good ADMET results, no significant affinity against CYP3A4, and general low toxicity. [ABSTRACT FROM AUTHOR]