Cytotoxic profile of natural and some modified bufadienolides from toad Rhinella schneideri parotoid gland secretion.
Cutaneous secretions of toad species are an important source of bufadienolides, compounds that exhibit interesting structural features and biopharmacological properties. Here we describe the isolation of bufadienolides from the Brazilian toad Rhinella schneideri parotoid glands secretion, including: marinobufagin (1), bufalin (2), telocinobufagin (3), hellebrigenin (4), and the atypical 20S,21R-epoxymarinobufagin (5) besides the widespread beta-sitosterol (6). Starting from natural bufadienolides four derivatives were prepared: 3beta-acetoxy-marinobufagin (7), 3beta-acetoxy-bufalin (8), 3beta-acetoxy-telocinobufagin (9), and 3beta-acetoxy-20S,21R-epoxymarinobufagin (10). The cytotoxic evaluation showed that all natural bufadienolides and their derivatives exhibited moderate to strong activity against human HL-60, SF-295, MDA-MB-435, and HCT-8 cancer cell strains without hemolysis of mouse erythrocytes. The acetylated bufadienolides (7-9) and the epoxide 10 showed lesser peripheral blood lymphocytes (PBLs) inhibitory activity than their precursors, suggesting that chemical modifications on such compounds can play an important role on the modulation of their cytotoxic profile.
Cunha-Filho
Geraldino A
GA
Laboratório de Isolamento e Transformação de Moléculas Orgânicas, Instituto de Química, Universidade de Brasília, Campus Universitário Darcy Ribeiro, 4478, CEP 70904-970, Asa Norte, Brasília-DF, Brazil.
Resck
Inês S
IS
Cavalcanti
Bruno C
BC
Pessoa
Cláudia O
CO
Moraes
Manoel O
MO
Ferreira
José R O
JR
Rodrigues
Felipe A R
FA
Dos Santos
Maria L
ML
D002018:Bufanolides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010306:Parotid Gland / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared
D002018:Bufanolides