TY - DATA T1 - First total synthesis of a novel amide alkaloid derived from Aconitum taipeicum and its anticancer activity PY - 2017/06/19 AU - Xinxin Zhang AU - Dandan Li AU - Xuanji Xue AU - Yan Zhang AU - Jie Zhang AU - Chen Huang AU - Zengjun Guo AU - Nigatu Tadesse UR - https://tandf.figshare.com/articles/journal_contribution/First_total_synthesis_of_a_novel_amide_alkaloid_derived_from_i_Aconitum_taipeicum_i_and_its_anticancer_activity/5117347 DO - 10.6084/m9.figshare.5117347 L4 - https://ndownloader.figshare.com/files/8697370 KW - Total synthesis KW - ITPD KW - Aconitum taipeicum KW - anticancer KW - apoptosis N2 - A concise total synthesis of a naturally occurring 3-isopropyl-tetrahydropyrrolo[1, 2-a]pyrimidine-2, 4(1H, 3H)-dione (ITPD) isolated from Aconitum taipeicum with a three-step approach was depicted in this study for the first time. Two key intermediates, diethyl isopropylmalonate (2) and pyrrolidin-2-amine (3), being synthsesised separately from initial diethyl malonate (4) and 3, 4-dihydro-2H-pyrrol-5-amine (5), were utilised to obtain the compound entitled ITPD. ITPD showed a promising anticancer activity in vitro on SMMC-7721 cell lines. Flow cytometry and cell cycle analysis revealed that ITPD could induce apoptosis and cell cycle arrest in S phase. The occurrence of apoptosis possibly attributed to the mechanism that ITPD could mediate the mitochondrial pathway through activating caspase-3/9 and increasing the ratio of Bax/Bcl-2 to finally trigger cell apoptosis and DNA damage. Collectively, the possibility to produce sufficient quantity of synthetic ITPD provided the base for further bio-evaluation in vivo and in vitro. The bioactive assay suggested that it may be a potential candidate for further chemical optimisation and use in cancer therapy. ER -