In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF₂ adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl‐2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole‐based CUR–BF₂ and CUR compounds and their bis‐thiocyanato derivatives exhibited high anti‐proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI‐8226) with significantly lower IC₅₀ values versus healthy PBMC cells; they also exhibited higher anti‐proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD‐1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).

中文翻译：

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具有显着抗肿瘤活性的杂环姜黄素类化合物文库的合成，计算对接研究和生物学评估

在继续寻找具有抗肿瘤活性的姜黄素（CUR）化合物时，合成了一系列新的杂环CUR–BF ₂加合物和基于吲哚，苯并噻吩和苯并呋喃及其芳基吡唑的CUR化合物。进行了计算机对接研究，以比较与特定癌症相关的靶蛋白（即HER2，蛋白酶体，VEGFR，BRAF和Bcl-2）与已知抑制剂药物的结合效率。大多数都表现出非常好的结合亲和力，与已知抑制剂的结合亲和力相似，甚至更好。基于吲哚的CUR–BF ₂和CUR化合物及其双硫氰酸根衍生物通过体外生物测定针对一组60种癌细胞系，更具体地针对多发性骨髓瘤（MM）细胞系（KMS11，MM1.S和RPMI- 8226）与健康的PBMC细胞相比，IC ₅₀值明显更低；它们在人结肠直肠癌细胞（HCT116，HT29，DLD-1，RKO，SW837和Caco2）中也表现出比亲本姜黄素更高的抗增殖活性，同时在正常结肠细胞（CCD112CoN和CCD841CoN）中的细胞毒性显着降低。