Synthesis and cytotoxicity of novel 14α--(andrographolide-3-subsitutedisoxazole-5-carboxylate) derivatives.

Simple and efficient method was established for the synthesis of a new family of 14α--(andrographolide-3-subsitutedisoxazole-5-carboxylate) derivatives () from naturally occurring andrographolide () by selective esterification with propiolic acid at C-14 using protection and deprotection strategy followed by metal free 1,3-dipolar cycloaddition with aryl nitrile oxides. All the synthesised derivatives were tested for their cytotoxicity against HCT-15, HeLa and DU145 cell lines. Most of the compounds exhibited improved cytotoxic activity compared to the parent molecule andrographolide (), as the compounds , , , , and showed significant cytotoxicity against three cancer cell lines. Except the compound and , all the compounds did not inhibit the normal cell line (VERO). Based on these studies isoxazole ester derivatives at C-14 of andrographolide with various substitutions promoting anticancer activities and better safety profiles. Further studies in this direction with improved water solubility and oral bioavailability are in progress in future.