a 温州医科大学药学院 化学生物学研究中心 温州 325035; b 温州医科大学附属第一医院药剂科 温州 325000; c 暨南大学组织移植与免疫实验中心 广州 510632
Synthesis, Crystal Structure, Antitumor Activity of Spiro-heterocyclic Mono-carbonyl Analogues of Curcumin
Wu Jianzhanga, Weng Bixiaa, Qiu Peihonga, Cai Zhijiana,b, Fan Leia, Ying Shilonga, Zhang Xiuhuaa,b, Wu Xiaopinga,c, Liang Guanga
a Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou 325035; b Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000; b Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632
Abstract:To discover novel lead compounds with good antitumor activity and low toxicity, 14 spiroheterocycle mono-car- bonyl 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 ESI-MS, ESI-HRMS and 1H 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.