Biological activity of neosergeolide and isobrucein B (and two semi-synthetic derivatives) isolated from the Amazonian medicinal plant Picrolemma sprucei (Simaroubaceae)

In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). The...

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Published in:Memórias do Instituto Oswaldo Cruz Vol. 104; no. 1; pp. 48 - 56
Main Authors: Silva, Ellen CC, Cavalcanti, Bruno C, Amorim, Rodrigo CN, Lucena, Jorcilene F, Quadros, Dulcimar S, Tadei, Wanderli P, Montenegro, Raquel C, Costa-Lotufo, Letícia V, Pessoa, Cláudia, Moraes, Manoel O, Nunomura, Rita CS, Nunomura, Sergio M, Melo, Marcia RS, de Andrade-Neto, Valter F, Silva, Luiz Francisco R, Vieira, Pedro Paulo R, Pohlit, Adrian M
Format: Journal Article
Language:English
Published: Brazil Fundação Oswaldo Cruz, Fiocruz 01.02.2009
Instituto Oswaldo Cruz, Ministério da Saúde
Fundação Oswaldo Cruz (FIOCRUZ)
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ISSN:1678-8060, 0074-0276, 0074-0276, 1678-8060
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Abstract In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti , haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum . Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 µg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 µg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
AbstractList In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti , haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum . Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 µg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 µg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2) known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvici-dal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC sub(50) = 5-27 kg/L) and against multidrug-resistant P. falciparum K1 strain (IC sub(50) = 1.0-4.0 kg/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC sub(50) = 11.8 kg/L). Quassinoids 1 and 2 (LC sub(50) = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC sub(50) = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the. observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 µg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 µg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.
Author Amorim, Rodrigo CN
Vieira, Pedro Paulo R
Quadros, Dulcimar S
Cavalcanti, Bruno C
Pessoa, Cláudia
Montenegro, Raquel C
Silva, Luiz Francisco R
Pohlit, Adrian M
Nunomura, Sergio M
Melo, Marcia RS
Lucena, Jorcilene F
Tadei, Wanderli P
Costa-Lotufo, Letícia V
de Andrade-Neto, Valter F
Moraes, Manoel O
Nunomura, Rita CS
Silva, Ellen CC
AuthorAffiliation Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
Instituto Nacional de Pesquisas da Amazônia
Laboratório de Princípios Ativos da Amazônia
Universidade Federal do Ceará
Universidade Federal do Amazonas
Centro Federal de Educação Tecnológica do Amazonas
Universidade Federal do Rio Grande do Norte
AuthorAffiliation_xml – name: Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
– name: Laboratório de Princípios Ativos da Amazônia
– name: Universidade Federal do Rio Grande do Norte
– name: Universidade Federal do Amazonas
– name: Universidade Federal do Ceará
– name: Instituto Nacional de Pesquisas da Amazônia
– name: Centro Federal de Educação Tecnológica do Amazonas
Author_xml – sequence: 1
  fullname: Silva, Ellen CC
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  fullname: Cavalcanti, Bruno C
– sequence: 3
  fullname: Amorim, Rodrigo CN
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/19274376$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords 12-acetylneosergeolide
1,12-diacetylisobrucein B
isobrucein B
antimalarial
neosergeolide
cytotoxicity
larvicide
Language English
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Snippet In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and...
In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and...
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SubjectTerms 1,12-diacetylisobrucein B
12-acetylneosergeolide
Aedes - drug effects
Aedes aegypti
Animals
antimalarial
Artemia - drug effects
Artemia franciscana
cytotoxicity
Erythrocytes - drug effects
Hemolysis - drug effects
HL-60 Cells - drug effects
Humans
isobrucein B
larvicide
Lethal Dose 50
Mice
neosergeolide
neosergeolide - isobrucein B - 12-acetylneosergeolide - 1,12-diacetylisobrucein B - cytotoxicity - antimalarial - larvicide
PARASITOLOGY
Plants, Medicinal
Plasmodium falciparum
Plasmodium falciparum - drug effects
Quassins - isolation & purification
Quassins - pharmacology
Simaroubaceae
Simaroubaceae - chemistry
TROPICAL MEDICINE
Title Biological activity of neosergeolide and isobrucein B (and two semi-synthetic derivatives) isolated from the Amazonian medicinal plant Picrolemma sprucei (Simaroubaceae)
URI http://www.bioline.org.br/abstract?id=oc09008
https://www.ncbi.nlm.nih.gov/pubmed/19274376
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https://www.proquest.com/docview/67007735
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