2. Academic Validation
  3. Antibacterial and antitumoral properties of 1,2,3-triazolo fused triterpenes and their mechanism of inhibiting the proliferation of HL-60 cells

Antibacterial and antitumoral properties of 1,2,3-triazolo fused triterpenes and their mechanism of inhibiting the proliferation of HL-60 cells

  • Eur J Med Chem. 2021 Nov 15:224:113727. doi: 10.1016/j.ejmech.2021.113727.
Rui Wang 1,  Yang Li 2,  Haibo Hu 3,  Leentje Persoons 4,  Dirk Daelemans 4,  Steven De Jonghe 4,  Walter Luyten 3,  Besir Krasniqi 1,  Wim Dehaen 5
Affiliations

Affiliations

  • 1 Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium.
  • 2 Zhong Yuan Academy of Biological Medicine, Liaocheng People's Hospital, Liaocheng, 252000, PR China.
  • 3 Department of Biology, Animal Physiology and Neurobiology Section, KU Leuven, Naamsestraat 59, Box 2465, B-3000, Leuven, Belgium.
  • 4 KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49 - Box 1043, B-3000, Leuven, Belgium.
  • 5 Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium. Electronic address: wim.dehaen@kuleuven.be.
PMID: 34352711 DOI: 10.1016/j.ejmech.2021.113727
Abstract

Antimicrobial resistance and Cancer are two important problems affecting human health. Actively developing novel Antibiotics and Anticancer medicines is a priority. Natural Pentacyclic Triterpenoids have attracted wide attention due to their significant biological activities. In this study, a series of 1,2,3-triazolo fused triterpenoids (betulin, oleanolic acid and ursolic acid) were functionalized on the A-ring by an in-house developed multi-component triazolization reaction. The compounds were investigated for antitumoral activity in twelve Cancer cell lines and were also tested for Antibacterial activity against four bacteria. In terms of Anticancer effects, compounds 5b-f and 8a-d displayed strong cytotoxic activity in pancreatic adenocarcinoma (Capan-1), chronic myeloid leukemia (Hap-1), acute myeloid leukemia (HL-60), acute lymphoblastic leukemia (Jurkat) and non-Hodgkin lymphoma (Rec-1) cell lines. Among them, compound 5f exhibited the most potent antiproliferative effect on HL-60 cells. Further pharmacological research confirmed that compound 5f caused mitochondrial dysfunction and arrested the cell cycle in the G0/G1 phase to induce Apoptosis of HL-60 cells. In addition, compound 5f also induced Autophagy to inhibit the proliferation of HL-60 cells. Antibacterial screening revealed that compounds 2a-g and 5a-d showed modest activity against Gram-negative bacteria (Escherichia coli and Salmonella enterica subsp. enterica) with especially compounds 2c and 2d being potent inhibitors of Salmonella enterica subsp. enterica growth. Because of their promising Anticancer and Antibacterial activity, this series of compounds deserve further study.

Keywords

1,2,3-triazolo fused triterpenoids; Antibacterial; Anticancer; Apoptosis; Autophagy.

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