Benzoquinoline Derivatives: An Attractive Approach to Newly Small Molecules with Anticancer Activity

Liliana Oniciuc; Dorina Amăriucăi-Mantu; Dumitrela Diaconu; Violeta Mangalagiu; Ramona Danac; Vasilichia Antoci; Ionel I Mangalagiu

doi:10.3390/ijms24098124

Benzoquinoline Derivatives: An Attractive Approach to Newly Small Molecules with Anticancer Activity

Int J Mol Sci. 2023 May 1;24(9):8124. doi: 10.3390/ijms24098124.

Authors

Liliana Oniciuc¹, Dorina Amăriucăi-Mantu¹, Dumitrela Diaconu^{1

2}, Violeta Mangalagiu², Ramona Danac¹, Vasilichia Antoci¹, Ionel I Mangalagiu^{1

2}

Affiliations

¹ Faculty of Chemistry, Alexandru Ioan Cuza University of Iasi, 11 Carol 1st Bvd, 700506 Iasi, Romania.
² Institute of Interdisciplinary Research-CERNESIM Center, Alexandru Ioan Cuza University of Iasi, 11 Carol I, 700506 Iasi, Romania.

Abstract

This study presents the synthesis, structural characterization, and in vitro evaluation of anticancer activity of some newly benzo[f]quinoline derivatives. The synthesis is facile and efficient, involving two steps: quaternization of nitrogen heterocycle followed by a [3+2] dipolar cycloaddition reaction. The synthesized compounds were characterized by FTIR, NMR, and X-ray diffraction on monocrystal in the case of compounds 6c and 7c. An in vitro single-dose anticancer assay of eighteen benzo[f]quinoline compounds, quaternary salts, and cycloadducts, was performed. The results showed that the most active compounds were quaternary salts 3d and 3f with aromatic R substituents. Quaternary salt 3d revealed non-selective activity against all types of cancer cells, while salt 3f exhibited a highly selective activity against leukemia cells. Compound 3d also presented remarkable cytotoxic efficiency against four distinct types of cancer cells-namely, non-small cell lung cancer HOP-92, melanoma LOX IMVI, melanoma SK-MEL-5, and breast cancer MDA-MB-468. Compound 3f was selected for five-dose screening. The study also includes SAR correlations.

Keywords: anticancer; benzo[f]quinoline derivatives; cycloadducts; quaternary salts.

MeSH terms

Antineoplastic Agents* / chemistry
Carcinoma, Non-Small-Cell Lung*
Cell Line, Tumor
Cell Proliferation
Drug Screening Assays, Antitumor
Humans
Lung Neoplasms*
Melanoma*
Molecular Structure
Quinolines* / chemistry
Quinolines* / pharmacology
Salts / pharmacology
Structure-Activity Relationship

Substances

Salts
Antineoplastic Agents
Quinolines

Grants and funding

This research was funded by a grant of the Romanian Ministry of Education and Research CNCS–UEFISCDI, project number PN–III–P4–IDPCE–2020–0371, within PNCDI III.