Novel phenyl and thiophene dispiro indenoquinoxaline pyrrolidine quinolones induced apoptosis via G1/S and G2/M phase cell cycle arrest in MCF-7 cells

New phenyl and thiophene dispiro indeno quinoxaline pyrrolidine quinolone analogues were synthesized by a one-pot four-component [3+2] cycloaddition reaction between (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones,o-phenylenediamine, ninhydrin, and benzylamine/thiophenemethylamine. The structure an...

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Published inNew journal of chemistry Vol. 44; no. 35; pp. 15031 - 15045
Main Authors Shyamsivappan, Selvaraj, Saravanan, Arjunan, Vivek, Raju, Suresh, Thangaraj, Shankar, Ramasamy, Gothandam, K. M., Mohan, Palathurai Subramaniam
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 21.09.2020
Royal Society of Chemistry
Subjects
Apoptosis
Cell cycle
Cell death
Chemistry
Chemistry, Multidisciplinary
Cycloaddition
Molecular docking
Ninhydrin
Phenylenediamine
Physical Sciences
Quinoxalines
Science & Technology
Stereochemistry
Stereoselectivity
IN-VITRO
VIVO
ANALOGS
INHIBITORS
CANCER
DERIVATIVES
STRUCTURE-BASED DESIGN
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Summary:New phenyl and thiophene dispiro indeno quinoxaline pyrrolidine quinolone analogues were synthesized by a one-pot four-component [3+2] cycloaddition reaction between (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones,o-phenylenediamine, ninhydrin, and benzylamine/thiophenemethylamine. The structure and regio- and stereochemistry of the compounds have been confirmed by various spectroscopic and X-ray diffraction analyses. The observed regio- and stereoselectivity of the compounds were further enlightened by DFT calculations. Further, thein vitrocytotoxic effects of the compounds were evaluated by MTT assay. The compounds exhibited significant inhibition activity towards the tested cancer cells HeLa and MCF-7. Among the synthesized compounds compound9eshowed the highest inhibitory potency against MCF-7 cells. Mechanistic cell death studies revealed that cell death was induced by9eagainst MCF-7 cells by ROS mediated G1/S and G2/M phase cell cycle arrest apoptosis. The apoptotic cell death was quantified by the annexin V-FITC/PI staining method. The binding mode of compound9ewas further examined byin silicomolecular docking studies.
ISSN:1144-0546
1369-9261
DOI:10.1039/d0nj02588g