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

Niggula Praveen Kumar; Shalini Nekkanti; S Sujana Kumari; Pankaj Sharma; Nagula Shankaraiah

doi:10.1016/j.bmcl.2017.04.022

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

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2369-2376. doi: 10.1016/j.bmcl.2017.04.022. Epub 2017 Apr 7.

Authors

Niggula Praveen Kumar¹, Shalini Nekkanti¹, S Sujana Kumari², Pankaj Sharma¹, Nagula Shankaraiah³

Affiliations

¹ Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
² Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
³ Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: [email protected].

PMID: 28431881
DOI: 10.1016/j.bmcl.2017.04.022

Abstract

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.

Keywords: 1,2,3-Triazoles; Click reaction; Cytotoxicity; DNA interaction; Phenanthrene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cycloaddition Reaction
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*
Phenanthrenes / chemical synthesis
Phenanthrenes / pharmacology*
Reactive Oxygen Species / metabolism
Triazoles / chemical synthesis
Triazoles / pharmacology*
Viscosity

Substances

2-((1-((2,3,6,7-tetramethoxyphenanthren-9-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo(de)isoquinoline-1,3(2H)-dione
Antineoplastic Agents
Fluorescent Dyes
Indoles
Intercalating Agents
Naphthalimides
Phenanthrenes
Reactive Oxygen Species
Triazoles
DAPI