Chinese Journal of Organic Chemistry >
Design, Synthesis, and Antitumor Activity of β-Carboline-Benzimidazole Hybrids
Received date: 2021-10-18
Revised date: 2021-12-23
Online published: 2022-01-11
Supported by
National Natural Science Foundation of China(22067017); Project of Innovation and Development from Shihezi University(CXFZ201904); Science Foundation for The Excellent Youth Scholars of Shihezi University(RCZK201933)
In a continuing effort to develop novel β-carboline derivatives endowed with better pharmacological profiles, a series of 1,9-disubstituted β-carboline-benzimidazole hybrids with various substituents were designed and synthesized from L-tryptophan and aldehydes. The target compounds were subjected to antitumor screening against five different cancer cell lines, namely, A549 (lung carcinoma), BGC-823 (gastric carcinoma), CT-26 (murine colon carcinoma), Bel-7402 (liver carcinoma), and MCF-7 (breast carcinoma), using standard methyl thiazolyl tetrazolium (MTT) assay. The structure-activity relationships (SARs) of the conjugates with different substituents at positions 1 and 9 in β-carbolines were also analyzed. The obtained results showed that most conjugates exhibited good cytotoxic activity against more than one cancer cell line. In particular, compound 5s with a benzyl group at position-9 and a trifluoromethyl substituent on the benzimidazole ring had the highest activity against MCF-7 cells (IC50 value of 4.9±0.3 μmol/L). Compounds 5c and 5q displayed significant cytotoxicity against three tumor cell lines, with IC50 values lower than 10 μmol/L. Moreover, these two compounds could moderately reduce the number of migrated cells at concentrations of 2.5~10 μg•mL–1.
Key words： β-carboline; benzimidazole; antitumor; structure-activity relationships
Siyu Zhu , Xinyu Huo , Qin Ma , Wei Chen , Jie Zhang , Liang Guo . Design, Synthesis, and Antitumor Activity of β-Carboline-Benzimidazole Hybrids[J]. Chinese Journal of Organic Chemistry, 2022 , 42(4) : 1129 -1135 . DOI: 10.6023/cjoc202110025
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