Synthesis and cytotoxic evaluation of novel indenoisoquinoline-substituted triazole hybrids

  • Bioorg Med Chem Lett. 2016 Aug 1;26(15):3652-7. doi: 10.1016/j.bmcl.2016.05.092.
Tham Pham Thi  1 ,  Thuy Giang Le Nhat  2 ,  Thuong Ngo Hanh  2 ,  Tan Luc Quang  3 ,  Chinh Pham The  4 ,  Tuyet Anh Dang Thi  2 ,  Ha Thanh Nguyen  2 ,  Thu Ha Nguyen  2 ,  Phuong Hoang Thi  2 ,  Tuyen Van Nguyen  5
Affiliations
  • 1. Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Thuyloi University, 175, Tay Son, Hanoi, Vietnam.
  • 2. Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
  • 3. Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Hanoi Pedagogical University No. 2, Vietnam.
  • 4. Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Thainguyen University of Science, Tanthinh, Thainguyen, Vietnam.
  • 5. Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. Electronic address: [email protected].
PMID: 27342752 DOI: 10.1016/j.bmcl.2016.05.092
Abstract

The synthesis of various substituted triazole-indenoisoquinoline hybrids was performed based on a CuI-catalyzed 1,3-cycloaddition between propargyl-substituted derivatives and the azide-containing indenoisoquinoline. Besides, a variety of N-(alkyl)propargylindenoisoquinolines was used as substrates for the construction of triazole-indenoisoquinoline-AZT conjugated via a click chemistry-mediated coupling with 3'-azido-3'-deoxythymidine (AZT). Thus, twenty three new indenoisoquinoline-substituted triazole hybrids were successfully prepared and evaluated as cytotoxic agents, revealing an interesting Anticancer activity of four triazole linker-indenoisoquinoline-AZT hybrids in KB and HepG2 Cancer cell lines.

Keywords
AZT; Cytotoxic agents; Hybrids; Indenoisoquinolines; Triazole.