Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.
Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.
Department of Chemistry and Center of Excellence for Innnovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. Electronic address: kwanruthai.t@psu.ac.th.
Kwanruthai
K
Tadpetch
Department of Chemistry and Center of Excellence for Innnovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Benyapa
B
Kaewmee
Department of Chemistry and Center of Excellence for Innnovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Kittisak
K
Chantakaew
Department of Chemistry and Center of Excellence for Innnovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Kawalee
K
Kantee
Department of Chemistry and Center of Excellence for Innnovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Vatcharin
V
Rukachaisirikul
Department of Microbiology and Natural Products Research Center of Excellence, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Souwalak
S
Phongpaichit
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007624:KB Cells; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014709:Vero Cells; D015025:Zearalenone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015025:Zearalenone
Cytotoxicity; Structure modification; Structure–activity relationship; Zearalenone