Synthesis and Cytotoxicity of Novel Analogues of Podophyllotoxin

Abstract

We have synthesized four novel derivatives of podophyllotoxin, the chalcone derivatives namely 2-benzylidene-6,7-dimethoxy-4-phenyl-3,4-dihydro-2H-naphthalen-1-one (4a), 2-benzylidene-5,7-dichloro-6-hydroxy-4-phenyl-3,4-dihydro-2H-naphthalen-1-one(4b), and the amino-thiazolyl derivatives namely7,8-dimethoxy-5-phenyl-4,5-dihydro-naphtha[1,2-d] thiazol-2-yl amine (5a) and 2-amino-6,8-dichloro-5-phenyl-4,5-dihydro-naphtho[1,2-d] thiazol-7-ol (5b). The aryl tetralin ring system in these compounds were attached to a fused aminothiazolyl ring or a chalcone ring. Synthesis of the tetralin ring in these podophyllotoxin derivatives was accomplished by the cyclization of the γ-hydroxyketones. These derivatives were evaluated for the induction of cytotoxicity in mouse mammary carcinoma cells in vitro. All the four compounds exhibited time dependent cytotoxicity at a concentration of 100μM when assessed by Trypan blue dye exclusion assay on Ehrlich Ascites Tumor (EAT) cells in vitro.