Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells

Xiao Lin; Xiao Lin; Yongjun Zhou; Liyun Liu; Hongrui Zhu; Yeping Chen; Shuping Wang; Fan Sun; Ling Chai; Buming Liu; Shihai Xu; Hou-Wen Lin

doi:10.3389/fchem.2019.00481

Frontiers in Chemistry (Jul 2019)

Compound Discovery and Structure-Activity Relationship Study of Neoantimycins Against Drug-Resistant Cancer Cells

Xiao Lin,
Xiao Lin,
Yongjun Zhou,
Liyun Liu,
Hongrui Zhu,
Yeping Chen,
Shuping Wang,
Fan Sun,
Ling Chai,
Buming Liu,
Shihai Xu,
Hou-Wen Lin

Affiliations

Xiao Lin: College of Chemistry and Materials, Jinan University, Guangzhou, China
Xiao Lin: College of Pharmacy, Jinan University, Guangzhou, China
Yongjun Zhou: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Liyun Liu: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Hongrui Zhu: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Yeping Chen: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Shuping Wang: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Fan Sun: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Ling Chai: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, China
Buming Liu: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, China
Shihai Xu: College of Pharmacy, Jinan University, Guangzhou, China
Hou-Wen Lin: State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacy, Research Center for Marine Drugs, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China

DOI: https://doi.org/10.3389/fchem.2019.00481
Journal volume & issue: Vol. 7

Abstract

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Four neoantimycins H-K (1–4) with C1-keto, including the new ones (1–2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5–8) in vitro, the absolute structures of 1–8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.

Published in Frontiers in Chemistry

ISSN: 2296-2646 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Chemistry
Website: http://journal.frontiersin.org/journal/chemistry

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