Antileukemic effects of Didemnum psammatodes (Tunicata: Ascidiacea) constituents.
Chemical investigation of the methanolic extract of the ascidian Didemnum psammatodes has led to the identification of fourteen known compounds: three methyl esters (methyl myristate, methyl palmitate and methyl stearate), four steroids (cholesterol, campesterol, stigmasterol and beta-sitosterol), two fatty acids (palmitic acid and stearic acid), three glyceryl ethers {(1,2-propanediol, 3-(heptadecyloxy), batyl alcohol and 1,2-propanediol, 3-[(methyloctadecyl)oxy]} and two nucleosides (thymidine and 2'-deoxyguanosine). Their structures were proposed by NMR and comparison with literature data and GC analysis in comparison with authentic sample. The cytotoxic activity of these compounds was evaluated against human leukemia cell line panel using the MTT assay. The mixture of the three methyl esters was the most active group of compounds, showing antiproliferative and cytotoxic effects. Further studies on their mode of action suggest that these activities are connected with inhibition of DNA synthesis and induction of both necrosis and apoptosis.
Takeara
Renata
R
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
Jimenez
Paula Christine
PC
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.
Wilke
Diego Veras
DV
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.
Odorico de Moraes
Manoel
M
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.
Pessoa
Cláudia
C
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil.
Peporine Lopes
Norberto
N
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
Lopes
João Luis Callegari
JLC
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
Monteiro da Cruz Lotufo
Tito
T
Instituto de Ciências do Mar, Universidade Federal do Ceará, Av. Abolição 3207, 60165-082, Fortaleza, Ceará, Brazil.
Costa-Lotufo
Letícia Veras
LV
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, P.O. Box-3157, 60430-270, Fortaleza, Ceará, Brazil. Electronic address: lvcosta@secrel.com.br.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015458:Leukemia, T-Cell; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D014561:Urochordata / Q000737:chemistry*
D003603:Cytotoxins; D004952:Esters; D010455:Peptides