Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

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Taki, Aya C
Brkljaca, Robert
Wang, Tao
Koehler, Anson
Ma, Guangxu
Danne, Jill
Ellis, Sarah
Hofmann, Andreas
Chang, Bill CH
Jabbar, Abdul
Urban, Sylvia
Gasser, Robin B
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2020
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Abstract

Eight secondary metabolites (1 to 8) were isolated from a marine sponge, a marine alga and three terrestrial plants collected in Australia and subsequently chemically characterised. Here, these natural product-derived compounds were screened for in vitro-anthelmintic activity against the larvae and adult stages of Haemonchus contortus (barber’s pole worm)—a highly pathogenic parasitic nematode of ruminants. Using an optimised, whole-organism screening system, compounds were tested on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s). Anthelmintic activity was initially evaluated on these stages based on the inhibition of motility, development and/or changes in morphology (phenotype). We identified two compounds, 6-undecylsalicylic acid (3) and 6-tridecylsalicylic acid (4) isolated from the marine brown alga, Caulocystis cephalornithos, with inhibitory effects on xL3 and L4 motility and larval development, and the induction of a “skinny-straight” phenotype. Subsequent testing showed that these two compounds had an acute nematocidal effect (within 1–12 h) on adult males and females of H. contortus. Ultrastructural analysis of adult worms treated with compound 4 revealed significant damage to subcuticular musculature and associated tissues and cellular organelles including mitochondria. In conclusion, the present study has discovered two algal compounds possessing acute anthelmintic effects and with potential for hit-to-lead progression. Future work should focus on undertaking a structure-activity relationship study and on elucidating the mode(s) of action of optimised compounds.

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Pathogens

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9

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7

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Immunology

Medical microbiology

Science & Technology

Life Sciences & Biomedicine

Microbiology

algae

Caulocystis cephalornithos

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Taki, AC; Brkljaca, R; Wang, T; Koehler, A; Ma, G; Danne, J; Ellis, S; Hofmann, A; Chang, BCH; Jabbar, A; Urban, S; Gasser, RB, Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus, Pathogens, 2020, 9 (7), pp. 550

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