Synthesis and anti-proliferative activity of novel azazerumbone conjugates with chalcones

  • Bioorg Med Chem Lett. 2015 Nov 15;25(22):5182-5. doi: 10.1016/j.bmcl.2015.09.069.
Vuong Van Truong  1 ,  Tran Duy Nam  1 ,  Truong Ngoc Hung  2 ,  Nguyen Thi Nga  2 ,  Pham Minh Quan  2 ,  Luu Van Chinh  3 ,  Sang-Hun Jung  4
Affiliations
  • 1. Vietnam-Russia Tropical Centre, 2-Nguyen Van Huyen, Cau Giay, Hanoi, Viet Nam.
  • 2. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
  • 3. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 4. College of Pharmacy and Institute of Drug Research and development, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: [email protected].
PMID: 26459207 DOI: 10.1016/j.bmcl.2015.09.069
Abstract

The conjugation of azazerumbone ((3E,7E,11E)-5,5,8,12-tetramethylazacyclododeca-3,7,11-trien-2-one (7)) and 2,4-dihydroxychalcones was carried out for the preparation of novel target compounds 9a-g with 1-ethylene-4-methylene-1,2,3-triazole linker and 10a-f with propylene linker between amide nitrogen of azazerumbone and 4-hydroxy group of chalcone. The anti-proliferative activity of these compounds against the LU-1, Hep-G2, MCF-7 and SW480 human Cancer cell lines were significantly improved compared to those of azazerumbone or zerumbone. The anti-proliferative activities of (3E,7E,11E)-1-((1-(2-(3-hydroxy-4-((E)-3-(3-methoxyphenyl)acryloyl)phenoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-5,5,8,12-tetramethyl azacyclododeca-3,7,11-trien-2-one (9b) and (3E,7E,11E)-1-(3-(4-((E)-3-(3,4,5-trimethoxyphenyl)acryloyl)phenoxy)propyl)-5,5,8,12-tetramethylazacyclododeca-3,7,11-trien-2-one (10d) are nearly comparable to those of ellipticine.

Keywords
Anti-proliferative activity; Azazerumbone; Chalcone; Conjugate; Zerumbone.