1. Synthesis and biological evaluation of echinomycin analogues as potential colon cancer agent.
- Author
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Kojima, Keita, Konishi, Hiroaki, Momosaki, Kyoka, Komatani, Yuya, Katsuyama, Akira, Nakagawa, Koji, Kanamitsu, Kayoko, Yakushiji, Fumika, Fujiya, Mikihiro, and Ichikawa, Satoshi
- Subjects
COLON cancer ,BIOSYNTHESIS ,CELL cycle regulation ,COLORECTAL cancer ,CANCER cells ,PEPTIDES ,CELL death - Abstract
Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription. Notably, transcriptome analysis indicated that the cell cycle and its regulation were involved in the effects on cells treated with 3. Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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