Design and synthesis of 1,2,3-triazolo-phenanthrene hybrids as cytotoxic agents

[Display omitted] A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostat...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2017-06, Vol.27 (11), p.2369-2376
Main Authors: Kumar, Niggula Praveen, Nekkanti, Shalini, Sujana Kumari, S., Sharma, Pankaj, Shankaraiah, Nagula
Format: Article
Language:English
Subjects:
1,2,3-Triazoles
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Line, Tumor
Click reaction
Cycloaddition Reaction
Cytotoxicity
DNA interaction
Fluorescent Dyes
G1 Phase Cell Cycle Checkpoints - drug effects
Humans
Indoles
Intercalating Agents - chemical synthesis
Intercalating Agents - pharmacology
Membrane Potential, Mitochondrial - drug effects
Microscopy, Phase-Contrast
Molecular Docking Simulation
Naphthalimides - chemical synthesis
Naphthalimides - pharmacology
Phenanthrene
Phenanthrenes - chemical synthesis
Phenanthrenes - pharmacology
Reactive Oxygen Species - metabolism
Triazoles - chemical synthesis
Triazoles - pharmacology
Viscosity
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Summary:[Display omitted] A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC-27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest cytotoxicity against DU145 cells with IC50 value of 1.5±0.09µM. Further, the cell cycle analysis shown that it blocks G0/G1 phase of the cell cycle in a dose dependent manner. In order to determine the effect of compound on cell viability, phase contrast microscopy, AO/EB, DAPI, DCFDA and JC-1 staining studies were performed. These studies clearly indicated that the compound 7d inhibited the cell proliferation of DU145 cells. Relative viscosity measurements and molecular docking studies indicated that these compounds bind to DNA by intercalation.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.04.022