Synthesis and biological evaluation of (-)-kunstleramide and its derivatives.
Venkateshwarlu R, Chinnababu B, Ramulu U, Purushotham Reddy K, Damoder Reddy M, Sowjanya P, Venkateswara Rao P, Aravind S.
Stereoselective total synthesis of (-)-kunstleramide, a cytotoxic dienamide from the bark of <i>Beilschmiedia kunstleri</i> gamble, has been accomplished by using Keck's asymmetric allylation and Trost isomerization as key reactions. Application of the developed strategy for the synthesis of a series of amide analogues (<b>8-22</b>) was also reported. Furthermore, the synthesized compounds were evaluated for their <i>in vitro</i> anti-proliferative activities against human epithelial lung carcinoma (A549), human epithelial cervical cancer (HeLa), human breast adenocarcinoma (MCF7) and human neuroblastoma (IMR32) cell lines using the SRB assay. All the compounds show moderate anti-proliferative activity against all cell lines. Some of the piperazine derivatives (<b>17-22</b>) strongly inhibit the growth of breast cancer cells with IC<sub>50</sub> values of 8-20 μM.