AUTHOR=Mahmoud Abdelhalim Babiker , Danton Ombeline , Kaiser Marcel , Khalid Sami , Hamburger Matthias , Mäser Pascal 

TITLE=HPLC-Based Activity Profiling for Antiprotozoal Compounds in Croton gratissimus and Cuscuta hyalina

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.01246

DOI=10.3389/fphar.2020.01246

ISSN=1663-9812

ABSTRACT=<p>In a screening of Sudanese medicinal plants for antiprotozoal activity, the chloroform fractions obtained by liquid-liquid partitioning from ethanolic extracts of fruits of <italic>Croton gratissimus</italic> var. <italic>gratissimus</italic> and stems of <italic>Cuscuta hyalina</italic> Roth ex Schult. exhibited <italic>in vitro</italic> activity against axenically grown <italic>Leishmania donovani</italic> amastigotes. This antileishmanial activity was localized by HPLC-based activity profiling. Targeted preparative isolation afforded flavonoids <bold>1</bold>–<bold>6</bold>, 3-methoxy-4-hydroxybenzoic acid (<bold>7</bold>), and benzyltetrahydroisoquinoline alkaloids laudanine (<bold>8</bold>) and laudanosine (<bold>9</bold>) from <italic>C. gratissimus</italic>, and pinoresinol (<bold>10</bold>), isorhamnetin (<bold>11</bold>), (-)-pseudosemiglabrin (<bold>12</bold>), and kaempferol (<bold>13</bold>) from <italic>C. hyalina.</italic> The antiprotozoal activity of <bold>1</bold>–<bold>13</bold> against <italic>L. donovani</italic> (axenic and intracellular amastigotes), <italic>Trypanosoma brucei rhodesiense</italic> (bloodstream forms), and <italic>Plasmodium falciparum</italic> (erythrocytic stages), and the cytotoxicity in L6 murine myoblast cells were determined <italic>in vitro</italic>. Quercetin-3,7-dimethylether (<bold>6</bold>) showed the highest activity against axenic <italic>L. donovani</italic> (IC<sub>50,</sub> 4.5 µM; selectivity index [SI], 12.3), <italic>P. falciparum</italic> (IC<sub>50,</sub> 7.3 µM; SI, 7.6), and <italic>T. b. rhodesiense</italic> (IC<sub>50</sub>, 2.4 µM; SI, 23.2). The congener ayanin (<bold>2</bold>) exhibited moderate antileishmanial (IC<sub>50</sub>, 8.2 µM; SI, 12.2), antiplasmodial (IC<sub>50</sub>, 7.8 µM; SI, 12.9), and antitrypanosomal activity (IC<sub>50</sub>, 11.2 µM; SI, 8.9). None of the compounds showed notable activity against the intramacrophage form of <italic>L. donovani</italic>.</p>