Synthesis and cytotoxic evaluation of novel indenoisoquinoline-substituted triazole hybrids

Tham Pham Thi; Thuy Giang Le Nhat; Thuong Ngo Hanh; Tan Luc Quang; Chinh Pham The; Tuyet Anh Dang Thi; Ha Thanh Nguyen; Thu Ha Nguyen; Phuong Hoang Thi; Tuyen Van Nguyen

doi:10.1016/j.bmcl.2016.05.092

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. Epub 2016 Jun 1.

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: ngvtuyen@hotmail.com.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Isoquinolines / chemistry
Isoquinolines / pharmacology*
KB Cells
Molecular Structure
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Antineoplastic Agents
Isoquinolines
Triazoles