Synthesis and Cytotoxic Activity of 12-Methyleneurea-14-deoxyandrographolide Derivatives

AimTo modify the chemical structure of andrographolide by introducing hydrophilic groups, evaluate cytotoxic activity and study the structure-activity relationship of the derivatives.MethodsKey intermediate 2 was synthesized via Michael addition and reduction, followed by reacting with isocyanates to get 3a–3n. The compounds were evaluated for cytotoxic activity and NA (neuraminidase of H1N1) inhibition.ResultsTwo derivatives (3f and 3m, both containing a single substituted aromatic ring) showed moderate cytotoxic activity while none of the compounds inhibited NA in the preliminary screening.ConclusionIntroducing aromatic ring at C-12 is advisable but the substituent can not be too large. Hydrophilic groups introduced to C-12 did not help to enhance the cyctotoxic activity, further study is in process.