Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin

To discover novel lead compounds with good antitumor activity and low toxicity, 14 spiroheterocycle mono-carbonyl analogs of curcumin (MCACs) were synthesized by 1,3-dipolar cycloaddition reaction. The one-pot reaction was carried out without catalyst, which showed the advantage of environmentally friendly. The structures of all compounds were characterized by BSI-MS, ESI-HRMS and H-1 NMR. The crystal structure of B6 was confirmed as monoclinic system by X-ray diffraction, which indicated high region-selectivity and stereo-selectivity in the reaction of these compounds. All compounds were screened for their abilities to inhibit the growth of human gastric cell SGC-7901, glioma cell U251, human large cell lung cancer cell lines NCI-H460 by thiazolyl blue tetrazolium bromide (MTT) assay, and some of them showed good antitumor activity. Among the active compounds, B1, B6, B7 and B11 exhibited strong antitumor efficacy on the three tumor cells and low cytotoxicity against human liver cells HL-7702. Both compounds B1 and B7 can significantly induce the activation of apoptosis related proteins cysteinyl aspartate specific proteinase (caspase3) and poly ADP-ribose polymerase (PARP), and induce the apoptosis of tumor cell. The synthesized spiro heterocycles derived from MCACs in this study were novel antitumor compounds, and these compounds appeared to possess good research prospect in the area of anti-tumor drugs.