<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>The arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.</p></sec><sec><h3>Objectives</h3><p>To determine the oxidant-scavenging activities and antiproliferative activity of (2<italic>E</italic>)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1<italic>H</italic>-inden-1-one (MLT-401), an arylidene indanone derivative.</p></sec><sec><h3>Methods</h3><p>Jurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.</p></sec><sec><h3>Results</h3><p>The antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI<sub>50</sub>) of 341.5 nM, being 12- and 9-fold less than GI<sub>50</sub> concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G<sub>0</sub>/G<sub>1</sub> cells after MLT-401 treatment. Mitochondrial membrane-bound Na<sup>+</sup>/K<sup>+</sup> ATPase, Ca<sup>2+</sup> ATPase, and Mg<sup>2+</sup> ATPase activities were inhibited by MLT-401 in a dose-dependent manner.</p></sec><sec><h3>Conclusion</h3><p>MLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.</p></sec></abstract>

BackgroundThe arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.ObjectivesTo determine the oxidant-scavenging activities and antiproliferative activity of (2E)-2-benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), an arylidene indanone derivative.MethodsJurkat cells, primary lymphocytes, and Vero cells were treated with MLT-401. Antioxidant properties of MLT-401 were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS)-based, and ferric-reducing antioxidant potential (FRAP) assays. Inhibition of cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based assay. Nuclear status was determined using a DNA fragmentation assay, and cell cycle stage was analyzed by flow cytometry. Mitochondrial membrane enzyme activities were measured using colorimetric methods.ResultsThe antioxidant assays gave MLT-401 half maximal inhibitory concentration (IC50) values of 1611 nM (DPPH-based assay), 2115 nM (ABTS-based assay), and 1586 nM (FRAP assay). MLT-401 inhibited proliferation of Jurkat cells with a concentration for 50% of maximal inhibition of cell proliferation (GI50) of 341.5 nM, being 12- and 9-fold less than GI50 concentrations for normal lymphocytes and Vero cells, respectively. MLT-401 caused nuclear fragmentation and DNA laddering as seen by electrophoresis. Jurkat cells showed a time-dependent accumulation of sub G0/G1 cells after MLT-401 treatment. Mitochondrial membrane-bound Na+/K+ ATPase, Ca2+ ATPase, and Mg2+ ATPase activities were inhibited by MLT-401 in a dose-dependent manner.ConclusionMLT-401 possesses significant antiproliferative activity and scavenges free radicals released through mitochondrial membrane damage in a Jurkat cell line model of cancer cells. Further investigation of MLT-401 as a chemotherapeutic anticancer agent and development of other arylidene indanone analogues are warranted. A detailed elucidation of mechanistic pathways is required for further development.

(2<italic>E</italic>)-2-Benzylidene-4,7-dimethyl-2,3-dihydro-1<italic>H</italic>-inden-1-one (MLT-401), a novel arylidene indanone derivative, scavenges free radicals and exhibits antiproliferative activity of Jurkat cells

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences

Center for Stem Cell Research, College of Medicine

Department of Microbiology and Clinical Parasitology, College of Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

(2)-2-Benzylidene-4,7-dimethyl-2,3-dihydro-1-inden-1-one (MLT-401), a novel arylidene indanone derivative, scavenges free radicals and exhibits antiproliferative activity of Jurkat cells

BackgroundThe arylidene indanone scaffold has contributed many lead molecules in chemotherapeutic anticancer agent research.ObjectivesTo determine the...

(2E)-2-Benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), a novel arylidene indanone derivative, scavenges free radicals and exhibits antiproliferative activity of Jurkat cells

Article Category: Original article

Publicado en línea: 31 mar 2020

Páginas: 131 - 139

DOI: https://doi.org/10.1515/abm-2019-0052

Palabras clave
antioxidants, antitumor drugs, antitumor drug screens, ATPases, indanones

© 2019 Prasanna Rajagopalan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

(2E)-2-Benzylidene-4,7-dimethyl-2,3-dihydro-1H-inden-1-one (MLT-401), a novel arylidene indanone derivative, scavenges free radicals and exhibits antiproliferative activity of Jurkat cells

Article Category: Original article

Publicado en línea: 31 mar 2020

Páginas: 131 - 139

DOI: https://doi.org/10.1515/abm-2019-0052

Palabras claveantioxidants, antitumor drugs, antitumor drug screens, ATPases, indanones

© 2019 Prasanna Rajagopalan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Palabras clave
antioxidants, antitumor drugs, antitumor drug screens, ATPases, indanones