Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging

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.

Photoactive and Luminescent Transition Metal Complexes as Anticancer Agents: A Guiding Light in the Search for New and Improved Cancer Treatments

“…A group of six inert iridium(III) complexes also exhibited nucleic-acid-binding properties, but fluorescent studies show that they accumulate in the actin cortex rather than the nucleus (Figure 4: IR19) [43]. There are several recent examples of iridium(III) complexes that interact with the endoplasmic reticulum; a group primarily focused on organic light-emitting diodes (OLEDs) was "swayed to the dark side" (to inorganic chemistry) using iridium complexes conjugated to guanidine and thiourea ligands (Figure 4: IR20) [44]. These inorganic complexes showed more consistent IC 50 values across cell lines compared to their organic counterpart.…”

Complexes of 1,3-Diisobutyl Thiourea with Copper(I), Zinc(II) and Mercury(II): Their Antioxidant and Antibacterial Evaluation

“…FT-IR spectra of complexes were recorded by the SHIMADZU model 8400s as KBr pellets, in the range 4000-400 cm −1 . The EIMS analyses were carried out with the help of a FOCUS DSQ (thermo) mass spectrometer and the m/z refer to isotopes 1 H and 12 C, 14 N, and 63 Cu. The crystal structure of complex 1 and 2 was determined by STOE IPDSII, fitted with a low-temperature unit.…”

“…Metal ions should be biologically acceptable, and their complex is supposed to tolerate physiological conditions for better efficiency. Since thiourea is the active part of bioorganic chemistry for a handsome number of applications, its selection as a ligand raises no question [13][14][15][16]. Complexes with late transition metals, such as Zn and Hg, possess photoluminescence properties and applications in nonlinear optics [17][18][19].…”

Supramolecular behaviour and fluorescence of rhodamine-functionalised ROMP polymers

“…Previous work in our laboratories has focused on polymer-drug conjugates 23,24 and we wished to explore the incorporation of fluorophores 25 as these have a range of important medical applications, enabling visualisation of cellular uptake, and are complementary to our luminescence investigations of uptake of potential therapeutics in resistant cancer lines. 26 We were particularly interested in self-assembled systems which possess "stealth" properties and to this end we used polyethylene glycol (PEG) as a clinically established copolymerisation adduct; PEG interacts minimally with biological fluid components, is hydrophilic, biologically inert, and can be used to control self-assembly outcomes, which in turn affects blood circulation and elimination. 5 Rhodamine B (RhB) was chosen as the fluorophore.…”