In vitro antiproliferative and apoptotic effects of thiosemicarbazones based on (-)-camphene and R-(+)-limonene in human melanoma cells

• Published in: PloS one Vol. 18; no. 11; p. e0295012
• Main Authors: Soares, Paula Roberta Otaviano, Passos, Débora Cristina Souza, da Silva, Francielly Moreira, da Silva-Giardini, Ana Paula B., Coelho, Narcimário Pereira, de Oliveira, Cecília Maria Alves, Kato, Lucília, da Silva, Cleuza Conceição, Guillo, Lidia
• Format: Journal Article
• Language: English
• Published: San Francisco, CA USA Public Library of Science 30.11.2023; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Medicine and Health Sciences; Physical Sciences; Research and Analysis Methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0295012

A series of 38 thiosemicarbazone derivatives based on camphene and limonene were evaluated for their antiproliferative activity. Among them, 19 were synthesized and characterized using proton and carbon-13 nuclear magnetic resonance ( 1 H and 13 C NMR). For initial compound selection, human melanoma cells (SK-MEL-37) were exposed to a single concentration of a compound (100 μM) for 24, 48, and 72 hours, and cell detachment was visually observed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Nineteen compounds ( 4, 6, 8, 11, 13, 14, 15, 16, 17, 18, 20, 22, 25, 26, 31, 3’, 4’, 6’, and 9’ ) yielded cell viability below 20%. Subsequently, IC 50 values for these compounds were determined, ranging from 11.56 to 55.38 μM, after 72 hours of treatment. Compound 17 (o- hydroxy benzaldehyde (-)-camphene-based thiosemicarbazone) demonstrated the lowest IC 50 value, followed by compound 4 (benzaldehyde (-) camphene-based thiosemicarbazone) at 12.84 μM. Regarding compound 4 , we observed the induction of a characteristic ladder pattern of DNA fragmentation through gel electrophoresis. Furthermore, fluorescence, flow cytometry and scanning microscopy assays revealed morphological changes consistent with apoptosis induction. Additionally, the measurement of caspase 6 and 8 activity in cellular extracts after treatment for 2, 4, 6, and 24 hours suggested the potential involvement of the extrinsic apoptosis pathway in the mechanism of action of compound 4 . Further investigations, including molecular docking studies, are required to fully explore the potential of compound 4 and the other selected compounds, highlighting their promising role in future melanoma therapy research.