Identification of fromiamycalin and halaminol A from Australian marine sponge extracts with anthelmintic activity against haemonchus contortus
- Herath, Dilrukshi, Preston, Sarah, Jabbar, Abdul, Garcia-Bustos, Jose, Taki, Aya, Addison, Russell, Hayes, Sasha, Beattie, Karren, McGee, Sean, Martin, Sheree, Ekin, Merrick, Hooper, John, Chang, Bill, Hofmann, Andreas, Davis, Rohan, Gasser, Robin
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Taki, Aya , Addison, Russell , Hayes, Sasha , Beattie, Karren , McGee, Sean , Martin, Sheree , Ekin, Merrick , Hooper, John , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Marine Drugs Vol. 17, no. 11 (Nov 2019), p. 14
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- Description: There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus - a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 +/- 0.74 mu M) and L4 motility (IC50 = 39.4 +/- 4.83 mu M), although it had a relatively low potency at inhibiting of xL3 motility (IC50 >= 100 mu M). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Taki, Aya , Addison, Russell , Hayes, Sasha , Beattie, Karren , McGee, Sean , Martin, Sheree , Ekin, Merrick , Hooper, John , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Marine Drugs Vol. 17, no. 11 (Nov 2019), p. 14
- Full Text:
- Reviewed:
- Description: There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus - a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 +/- 0.74 mu M) and L4 motility (IC50 = 39.4 +/- 4.83 mu M), although it had a relatively low potency at inhibiting of xL3 motility (IC50 >= 100 mu M). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.
Pharmaceutical pollution in marine waters and benthic flora of the southern Australian coastline
- Long, Benjamin, Harriage, Samantha, Schultz, Nick, Sherman, Craig, Thomas, Michael
- Authors: Long, Benjamin , Harriage, Samantha , Schultz, Nick , Sherman, Craig , Thomas, Michael
- Date: 2023
- Type: Text , Journal article
- Relation: Environmental chemistry Vol. 19, no. 6 (2023), p. 375-384
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- Description: Environmental context Most human pharmaceutical waste is discharged to the environment. While the presence of pharmaceuticals in freshwater systems is well documented globally, little is known of the impact on marine ecosystems. We measured pharmaceuticals in a marine environment in south-eastern Australia and found pharmaceutical concentrations around 24 000 times higher in benthic flora than in the marine surface waters. We discuss the potential use of seaweeds as biological indicators of pharmaceutical pollution. Rationale Pharmaceuticals are emerging pollutants of concern with a range of adverse consequences for organisms and ecosystems. Their presence in freshwater and estuarine systems has been well documented, but less is known about their prevalence in open ocean, or their uptake by benthic flora. This preliminary survey of the southern Australian coastline sought to measure the concentrations of key pharmaceuticals in both surface waters and benthic flora. Methodology This study used LC-MS/MS to measure the concentration carbamazepine, tramadol and venlafaxine in (1) samples from wastewater treatment plants, (2) ocean surface waters and (3) several species of benthic flora. Surface waters and benthic flora were sampled at two sites near waste water treatment plant (WWTP) discharges, and one site away from any discharge. Results All three pharmaceuticals were detected in surface water samples with their risk assessed (via risk quotient) as medium risk (carbamazepine) or low risk (venlafaxine, tramadol). All three pharmaceuticals were also detected in benthic flora, particularly in brown macroalgae Tramadol was measured at a maximum of 34.7 ng g
- Authors: Long, Benjamin , Harriage, Samantha , Schultz, Nick , Sherman, Craig , Thomas, Michael
- Date: 2023
- Type: Text , Journal article
- Relation: Environmental chemistry Vol. 19, no. 6 (2023), p. 375-384
- Full Text:
- Reviewed:
- Description: Environmental context Most human pharmaceutical waste is discharged to the environment. While the presence of pharmaceuticals in freshwater systems is well documented globally, little is known of the impact on marine ecosystems. We measured pharmaceuticals in a marine environment in south-eastern Australia and found pharmaceutical concentrations around 24 000 times higher in benthic flora than in the marine surface waters. We discuss the potential use of seaweeds as biological indicators of pharmaceutical pollution. Rationale Pharmaceuticals are emerging pollutants of concern with a range of adverse consequences for organisms and ecosystems. Their presence in freshwater and estuarine systems has been well documented, but less is known about their prevalence in open ocean, or their uptake by benthic flora. This preliminary survey of the southern Australian coastline sought to measure the concentrations of key pharmaceuticals in both surface waters and benthic flora. Methodology This study used LC-MS/MS to measure the concentration carbamazepine, tramadol and venlafaxine in (1) samples from wastewater treatment plants, (2) ocean surface waters and (3) several species of benthic flora. Surface waters and benthic flora were sampled at two sites near waste water treatment plant (WWTP) discharges, and one site away from any discharge. Results All three pharmaceuticals were detected in surface water samples with their risk assessed (via risk quotient) as medium risk (carbamazepine) or low risk (venlafaxine, tramadol). All three pharmaceuticals were also detected in benthic flora, particularly in brown macroalgae Tramadol was measured at a maximum of 34.7 ng g
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