Further drimane sesquiterpenes from Drimys brasiliensis stem barks with cytotoxic potential.
Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activitys and evaluates them in leukemia cells. The stem bark extract were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11α-enol-albicanol (1a) and the isomer 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11β-enol-albicanol (1b) and 1β-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), the mixture drimanial (5) and 1β-O-(p-methoxy-E-cinnamoyl)-6α-hydroxypolygodial (6) were also isolated. The drimanes (1-4) and drimanial (5), 1β-(p-coumaroyloxy)-polygodial (7), 1β-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 μM. 1-β-(p-cumaroiloxi)-polygodial showed the best result with IC50 8.18 and 3.56 μM by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-12.
Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, Itajaí, SC, CEP 88302-202, Brazil.
Eduarda
E
Fratoni
Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, Itajaí, SC, CEP 88302-202, Brazil.
Vanessa Duarte
VD
Claudino
Programa de Pós-Graduação em Química, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, CEP 88040-970, Brazil.
Rosendo Augusto
RA
Yunes
Centro Integrado de Pesquisas Oncohematológicas na Infância (CIPOI), UNICAMP, Campinas, SP, CEP 13083-970, Brazil.
Gilberto C
GC
Franchi
Centro Integrado de Pesquisas Oncohematológicas na Infância (CIPOI), UNICAMP, Campinas, SP, CEP 13083-970, Brazil.
Alexandre E
AE
Nowill
Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, Itajaí, SC, CEP 88302-202, Brazil.
Valdir Cechinel
VC
Filho
Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, Itajaí, SC, CEP 88302-202, Brazil.
Franco Delle
FD
Monache
Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí - UNIVALI, Itajaí, SC, CEP 88302-202, Brazil. angela@univali.br.
Angela
A
Malheiros
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D032424:Drimys / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal; D000081223:Polycyclic Sesquiterpenes; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C437376:drimane
Chromatography; Cytotoxic potential; Drimys brasiliensis; Phytochemistry; Sesquiterpenoids