Novel anticancer silver(I) phosphines proven to target the mitochondrial-mediated cell death pathway in malignant cells

Abstract: Cancer next to heart disease is the leading cause of death worldwide. It affects a large population of Africa and is regarded as a low public concern due to the prioritizing of other serious diseases (e.g. AIDS, malaria and tuberculosis) in the country. In 2008, over 680, 000 new cancer cases have been reported in Africa and over 500, 000 deaths of which these numbers could double by the year 2030. Apoptosis is an energy-dependant mechanism that is activated upon various stimuli that can either be external or internal of the cell. This form of cell death is the preferred route to induce malignant cell death because of the absence of an inflammatory response. Mutations in apoptotic genes, especially those from the p53 gene sub-family, are the main contributors of therapeutic resistance in most cancers. Although a wide range of anticancer regimens has been explored to kill of malignancies, in most cases, their approach has not been successful. Platinum-based treatments like, cisplatin and other derivatives, have been studied extensively as anticancer agents and is currently used (or in combination with other chemotherapeutic drugs) to treat certain malignancies. The use of these platinum agents is limited by their low selectivity and cancer resistance that occur over time. Phosphine transition metals, like gold(I), copper(I) and ruthenium(III) phosphines have been studied as potential anticancer agents. In addition, first-generation silver(I) phosphine complexes gardened interest due to their ease of structural manipulation that can improve anticancer activity. Some studies suggest that silver(I) phosphine complexes that are lipophilic in nature cause malignant cell death through mitochondrial targeting. Overall, the specific targeting mechanism of the silver(I) complex family is not known and should be elucidated to further understand their role in cancer cell death.Ph.D. (Biochemistry

Synthesis, crystal structure and spectral studies of silver(I) cyclohexyldiphenylphosphine complexes : towards the biological evaluation on malignant and non-malignant cells

Please read abstract in the article.The University Research Council of the University of Johannesburg, SASOL, and TESP.https://www.tandfonline.com/loi/gcoo202023-02-22hj2023Chemistr

Anticancer activity of silver(I) cyclohexyldiphenylphosphine complexes toward SNO cancer cells

<p>Silver and its derivatives have been and are currently used as antimicrobial and antibacterial agents. However, their use is rather limited to date as anticancer agents. Thus, this study focuses on the synthesis and characterization of three silver(I) complexes which have the ability to adopt different geometries, and to induce cancer cell death in SNO esophageal cancer cells. Silver thiocyanate was reacted in different ratios with cyclohexyldiphenylphosphine to obtain 1:1 (complex <b>1</b>), 1:2 (complex <b>2</b>), and 1:3 (complex <b>3</b>) molar ratios of silver(I):cyclohexyldiphenylphosphine complexes. These complexes were characterized using conventional spectroscopic techniques, which included ¹H, ¹³C, and ³¹P NMR, FTIR, and microanalysis (%C, H, N, S). In addition, the single-crystal X-ray structures of complexes <b>1</b> and <b>2</b> were determined. Moreover, all three complexes displayed toxic activity toward the malignant SNO cells with IC₅₀ concentrations below 5 μM as determined with an alamarBlue® viability assay. Morphological and flow cytometric analyses were included to identify the possible mode of cancer cell death. These biochemical assays revealed that all three treatments induced apoptosis due to the presence of specific apoptotic markers.</p