Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites
In the present study,13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivat...
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| Format: | Article |
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MDPI AG
2010-07-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/8/7/2162/ |
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| author | Deniz Tasdemir Michelle Tierney Marcel Kaiser Ernesto Fattorusso Orazio Taglialatela-Scafati Marialuisa Menna Fernando Scala |
| author_facet | Deniz Tasdemir Michelle Tierney Marcel Kaiser Ernesto Fattorusso Orazio Taglialatela-Scafati Marialuisa Menna Fernando Scala |
| author_sort | Deniz Tasdemir |
| collection | DOAJ |
| description | In the present study,13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas generahave been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds.In addition,evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids. |
| first_indexed | 2024-04-13T00:30:54Z |
| format | Article |
| id | doaj.art-3b9562a3e4bd4018a681eb9e088eb714 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T00:30:54Z |
| publishDate | 2010-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-3b9562a3e4bd4018a681eb9e088eb7142022-12-22T03:10:28ZengMDPI AGMarine Drugs1660-33972010-07-01872162217410.3390/md8072162Bromopyrrole Alkaloids as Lead Compounds against Protozoan ParasitesDeniz TasdemirMichelle TierneyMarcel KaiserErnesto FattorussoOrazio Taglialatela-ScafatiMarialuisa MennaFernando ScalaIn the present study,13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas generahave been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds.In addition,evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.http://www.mdpi.com/1660-3397/8/7/2162/bromopyrrole alkaloidsantiprotozoal activityenzyme inhibitionTrypanosomaLeishmaniaPlasmodium |
| spellingShingle | Deniz Tasdemir Michelle Tierney Marcel Kaiser Ernesto Fattorusso Orazio Taglialatela-Scafati Marialuisa Menna Fernando Scala Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites Marine Drugs bromopyrrole alkaloids antiprotozoal activity enzyme inhibition Trypanosoma Leishmania Plasmodium |
| title | Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites |
| title_full | Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites |
| title_fullStr | Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites |
| title_full_unstemmed | Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites |
| title_short | Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites |
| title_sort | bromopyrrole alkaloids as lead compounds against protozoan parasites |
| topic | bromopyrrole alkaloids antiprotozoal activity enzyme inhibition Trypanosoma Leishmania Plasmodium |
| url | http://www.mdpi.com/1660-3397/8/7/2162/ |
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