Synthesis and Anticancer Activity Assessment of Zelkovamycin Analogues
Xinrong Xie,
Hongshun Huang,
Yogini S. Jaiswal,
Shaoyang Su,
Linxia Yang,
Yu Fan,
Yifu Guan,
Leonard L. Williams,
Hedong Bian
Affiliations
Xinrong Xie
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
Hongshun Huang
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
Yogini S. Jaiswal
Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, The North Carolina Research Campus, Kannapolis, NC 28081, USA
Shaoyang Su
Department of Applied Chemistry Teaching and Research, Guangxi Vocational University of Agriculture, Nanning 530007, China
Linxia Yang
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
Yu Fan
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
Yifu Guan
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
Leonard L. Williams
Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, The North Carolina Research Campus, Kannapolis, NC 28081, USA
Hedong Bian
Key Laboratory of Chemistry and Engineering of Forest Products (State Ethnic Affairs Commission), Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China
The zelkovamycin family is a class of cyclic octapeptides with potent antibacterial and antiviral activity. Due to their unique chemical structures and excellent bioactivity, zelkovamycins have consistently attracted the interest of synthetic chemists. However, only the total synthesis of zelkovamycin and zelkovamycin G has been reported until now. The current work presents, for the first time, the synthesis of zelkovamycin analogues, along with their anticancer activity assessment. Firstly, the corresponding chain peptide based on the amino acid sequence of zelkovamycin H was synthesized using the Fmoc solid-phase peptide strategy. This was followed by cyclization under high dilution conditions to obtain compound 21, and its structure was elucidated by NMR analysis. The results confirm that compound 21 is not the natural product of zelkovamycin H. We deduced that during the synthesis of peptide 12, the D-Abu residue epimerized to the L-Abu form, leading to the formation of peptide 20, which blocked our efforts during the synthesis of zelkovamycin H. Two more analogues, 22 and 23, were synthesized by changing the structure of amino acid residues using the same strategy. The anticancer activity of analogues 21–23 against Huh-7 cells was evaluated in vitro; however, their IC50 values were >50 μM.
