Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol

Mixo  Aunny Sibiya; Lerato Raphoko; Dikgale Mangokoana; Raymond Makola; Winston Nxumalo; Thabe  Moses Matsebatlela

doi:10.3390/molecules24030407

Molecules (Jan 2019)

Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol

Mixo Aunny Sibiya,
Lerato Raphoko,
Dikgale Mangokoana,
Raymond Makola,
Winston Nxumalo,
Thabe Moses Matsebatlela

Affiliations

Mixo Aunny Sibiya: Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, University of Limpopo, Sovenga 0727, South Africa
Lerato Raphoko: Chemistry Department, School of Physical and Mineral Sciences, University of Limpopo, Sovenga 0727, South Africa
Dikgale Mangokoana: Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, University of Limpopo, Sovenga 0727, South Africa
Raymond Makola: Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, University of Limpopo, Sovenga 0727, South Africa
Winston Nxumalo: Chemistry Department, School of Physical and Mineral Sciences, University of Limpopo, Sovenga 0727, South Africa
Thabe Moses Matsebatlela: Department of Biochemistry, Microbiology and Biotechnology, School of Molecular and Life Sciences, University of Limpopo, Sovenga 0727, South Africa

DOI: https://doi.org/10.3390/molecules24030407
Journal volume & issue: Vol. 24, no. 3
p. 407

Abstract

Read online

Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising targeted and selective anticancer drug activity. Hence, this study was aimed at determining in vitro anticancer activity effects of a newly synthesized class of 3-(quinoxaline-3-yl) prop-2-ynyl quinoxaline derivatives on A549 lung cancer cells. An assessment of the quinoxaline derivatives ferric reducing power, free radical scavenging activity, cytotoxic activity, and ability to induce reactive oxygen species (ROS) production was performed using the Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assays, respectively. The ability of the quinoxaline derivatives to induce apoptosis in A549 cells was assessed using the Acridine Orange/Ethidium Bromide (AO/EB) and Annexin V-FITC/Dead Cell Assay. Of the four quinoxaline derivatives tested, 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate (LA-39B) and 3-(quinoxaline-3-yl) prop-2-yn-1-ol (LA-55) displayed a dose-dependent reducing power, free-radical scavenging activity, inhibition of cell viability, and stimulation of ROS production which was accompanied by induction of apoptosis in A549 lung cancer cells. None of the quinoxaline derivatives induced cell death or ROS production in non-cancerous Raw 267.4 macrophage cells. Cytotoxicity was observed in A549 lung cancer, HeLa cervical cancer, and MCF-7 breast cancer cells albeit inhibition was more pronounced in A549 cells. The results of the study suggest that 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate and 3-(quinoxaline-3-yl) prop-2-yn-1-ol induce apoptotic cell death in A549 lung cancer cells.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

About the journal

Abstract

Keywords