Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging. (20th December 2019)

• Record Type: Journal Article
• Authors: Thomas, Samuel J.; Balónová, Barbora; Cinatl, Jindrich; Wass, Mark N.; Serpell, Christopher J.; Blight, Barry A.; Michaelis, Martin
• Is Part Of: ChemMedChem. Volume 15:Number 4(2020)
• Page Start: 349
• Page End: 353
• Publication Date: 2019-12-20
• Subjects: drug resistance -- cancer -- metal complexes -- cellular imaging -- OLEDs; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201900591
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. Iridium complexes present new opportunities for drug development and imaging in terms of structure and photoactivity. We have systematically synthesised a set of thiourea and guanidine compounds and iridium complexes thereof, and elucidated structure–activity relationships for cellular toxicity in three ovarian cancer cell lines and their cisplatin‐resistant sub‐lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea‐, guanidine‐, and iridium‐based materials. Abstract : Patterns of toxicity : Thiourea and guanidine compounds, and iridium complexes thereof, have been screened against drug‐resistant cancer cell lines, showing toxicity against cisplatin‐resistant strains. The compounds display toxicity trends which are strongly dependent upon S/NH substitution. The patterns of toxicity are illuminated through use of the intrinsic luminescence of the complexes as a handle for cellular imaging.