4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibitors

Bioorg Med Chem Lett. 2020 May 15;30(10):127109. doi: 10.1016/j.bmcl.2020.127109.

Xingrui He ¹, Yuan Gao ², Zi Hui ³, Guodong Shen ⁴, Shuo Wang ⁴, Tian Xie ⁵, Xiang-Yang Ye ⁶

Affiliations

1 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, PR China; Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, PR China; Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, PR China; School of Pharmacy, School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong, 252000, PR China.
2 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, PR China; School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510000, PR China.
3 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, PR China; Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, PR China; Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, PR China.
4 School of Pharmacy, School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong, 252000, PR China.
5 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, PR China; Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, PR China; Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, PR China. Electronic address: [email protected].
6 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, PR China; Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, PR China; Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, PR China. Electronic address: [email protected].

PMID: 32201021 DOI: 10.1016/j.bmcl.2020.127109

Abstract

Histone lysine specific demethylase 1 (LSD1 or KDM1A) is a potential therapeutic target in oncology due to its overexpression in various human tumors. We report herein a new class of benzofuran acylhydrazones as potent LSD1 inhibitors. Among the 31 compounds prepared, 14 compounds exhibited excellent LSD1 inhibitory activity with IC₅₀ values ranging from 7.2 to 68.8 nM. In cellular assays, several compounds inhibited the proliferations of various Cancer cell lines, including PC-3, MCG-803, U87 MG, PANC-1, HT-29 and MCF-7. This opens up the opportunity for further optimization and investigation of this class compounds for potential Cancer treatment.

Keywords

Anti-tumor activity; Benzofuran; Epigenetics; Lysine-specific demethylase 1; N-acylhydrazone (NAH).

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