Synthesis of novel potent cytotoxicy podophyllotoxin-naphthoquinone compounds via microwave-assited multicomponent domino reactions

  • Bioorg Med Chem Lett. 2021 Apr 1:37:127841. doi: 10.1016/j.bmcl.2021.127841.
Quynh Giang Nguyen Thi  1 ,  Giang Le-Nhat-Thuy  2 ,  Tuyet Anh Dang Thi  3 ,  Phuong Hoang Thi  4 ,  Anh Nguyen Tuan  5 ,  Thu Ha Nguyen Thi  6 ,  Thanh Tra Nguyen  7 ,  Thanh Nguyen Ha  8 ,  Ha Hoang Mai  9 ,  Tuyen Van Nguyen  10
Affiliations
  • 1. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 2. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 3. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 4. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 5. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 6. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 7. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 8. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 9. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
  • 10. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
PMID: 33556568 DOI: 10.1016/j.bmcl.2021.127841
Abstract

A series of novel podophyllotoxin-naphthoquinone compounds 5a-p were synthesized in good yields using microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, aromatic benzaldehydes, tetronic acid and ammonium acetate. All the synthesized compounds were fully characterized by spectral data and evaluated for their cytotoxicity activities against KB, HepG2, Lu1, MCF7, and non-cancerous Hek-293 cell lines. Among 16 new compounds screened, compounds 5a, 5d, 5h, and 5k displayed high potent inhibitory activities with IC50 < 40 nM against HepG2 and SK-Lu-1 cell lines, and showed lower toxicity for non-cancerous Hek-293 cell line, demonstrating the potential importance of these compounds in the development of potential Anticancer agents.

Keywords
Azaanthraquinone; Cytotoxicic activity; Four-component reaction; Microwave-assisted reaction; Naphthoquinone; Podophyllotoxin derivatives.