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. 2019 May 14;5(5):e01603.
doi: 10.1016/j.heliyon.2019.e01603. eCollection 2019 May.

Novel 3-((2-chloroquinolin-3-yl)methylene)indolin-2-one derivatives produce anticancer efficacy in ovarian cancer in vitro

Chandrabose Karthikeyan  1   2 , Haneen Amawi  3   4 , Charles R Ashby Jr  5 , Vishwa M Khare  6 , Veronica Jones  7 , N S Hari Narayana Moorthy  1 , Piyush Trivedi  2   8 , Amit K Tiwari  3   7
Affiliations

Novel 3-((2-chloroquinolin-3-yl)methylene)indolin-2-one derivatives produce anticancer efficacy in ovarian cancer in vitro

Chandrabose Karthikeyan et al. Heliyon. .

Abstract

A novel series of 3-((2-chloroquinolin-3-yl)methylene)indolin-2-ones were synthesized, using the 'molecular hybridization approach' and evaluated for anticancer efficacy. Eleven 3-((2-chloroquinolin-3-yl)methylene)indolin-2-ones (LM01 to LM11) were synthesized and evaluated for in vitro cytotoxic efficacy in cancer (ovarian, prostate and colon) and two non-cancerous cell lines. Among the 3-((2-chloroquinolin-3-yl)methylene)indolin-2-one derivatives, LM08, with a 6-Cl substitution in the 3-quinolinyl moiety, had selective and potent cytotoxic efficacy in the ovarian cancer cell line A2780. Further mechanistic investigations indicated that LM08 significantly inhibited the clonogenic survival of A2780 cancer cells, which was mediated by inducing apoptosis.

Keywords: Natural product chemistry; Pharmaceutical chemistry; Pharmaceutical science.

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Figures

Fig. 1
Fig. 1
Representative examples of aryl/heteroarylidene indolin-2-ones reported as potent anticancer compounds.
Scheme 1
Scheme 1
Synthesis of 3-((2-chloroquinolin-3-yl)methylene)indolin-2-one derivatives (LM01 to LM11).
Fig. 2
Fig. 2
LM08 inhibits colony formation in A2780 cells. The cells were incubated with different concentrations of LM08 (10 or 20 μM) or vehicle. The pictures show the effect of LM08 on A2780 cells colony density and colony size. Each experiment was repeated independently in triplicate.
Fig. 3
Fig. 3
LM08 induces apoptosis in A2780 cells. A2780 cells in complete medium were incubated with LM08 at 10 or 20 μM or vehicle for 24 h. Cells were then incubated with annexin red dye and analyzed by flow cytometry. The representative results for A2780 cells are from at least two independent experiments, each performed in triplicate.
Fig. 4
Fig. 4
The effect of LM08 on the nuclear morphology of A2780 cells. The nuclear morphology changes in A2780 cells upon incubation with 5 or 10 μM of LM08 or vehicle for 24 or 48 h, respectively, were detected using DAPI staining. Condensed and fragmented nuclei were observed under an EVOS fluorescent microscope at 40X.
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