Gold complexes have al ong tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effectsh ave been confirmed. Herein,w e evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targetso fs evere acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugsw ere effectivei nhibitorso ft he interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2(ACE2) host receptor and might thusi nterfere with the viral entry process. The gold metallodrugsw ere also efficient inhibitors of the papain-like protease (PLpro) of SARS-CoV-1 and SARS-CoV-2, which is ak ey enzymei nt he viral replication. Regarding PLpro from SARS-CoV-2,t he here reportedi nhibitorsa re among the very first experimentally confirmed examples with activity against this target enzyme. Importantly,t he activity of the complexes against both PLpro enzymes correlated with the ability of the inhibitors to removez inc ions from the labile zinc center of the enzyme. Ta ken together,the results of this pilot study suggest further evaluation of gold complexes as SARS-CoV antiviral drugs.

Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a surge for new chemotherapeutic drugs. More specifically, the discovery of new drug candidates able to overcome severe side effects, the occurrence of resistance and the inefficacy toward metastatic tumours is highly desirable. In this work, we designed a new chemotherapeutic drug candidate against cancer, namely [Ru(DIP)2(sq)]PF6 (Ru-sq) (DIP = 4,7-diphenyl-1,10-phenanthroline; sq = semiquinonate ligand). The aim was to combine the great potential expressed by Ru(II) polypyridyl complexes and the singular redox and biological properties associated to the catecholate moiety. Several pieces of experimental evidence (e.g., X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrate that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinised in vitro and in vivo, and the results highlight the tremendous potential of this complex as a chemotherapeutic agent against cancer. Ru-sq was notably found have a much higher cytotoxic activity than cisplatin on several cell lines (i.e. in the nanomolar range), and, contrary to cisplatin, to have mitochondrial disfunction as one of its modes of action. The multicellular targets of Ru-sq could potentially be the key to overcome one of the main drawbacks of cisplatin i.e. the occurrence of resistance. Moreover, Ru-sq exhibited impressing activity on Multi Cellular Tumour Spheroids (MCTS) model, leading to a growth inhibition of the tumour even 13 days after treatment (20 μM). Very importantly, using two different in vivo models, it could be demonstrated that this compound is extremely well-tolerated by mice and has a very promising activity, curing, in some cases, tumour-bearing mice.<br>

A red light for cancer cells: an iron(III) complex (1, see picture) that contains an anthracenyl fluorophore moiety and a catecholate ligand is a potent, metal-based PDT agent that efficiently photocleaves DNA in near-infrared light, has significant nuclear uptake, and high photocytotoxicity in red light by an apoptotic pathway in HeLa and MCF-7 cancer cells.

The use of photodynamic therapy( PDT) to treat cancer has received increasing attention over the last years. However,the clinically used photosensitisers (PSs) have some limitations that include poor aqueous solubility,hepatotoxicity, photobleaching,a ggregation, and slow clearance from the body,sothe design of new classes of PSs is of great interest. We present the use of bis(dipyrrinato)zinc(II) complexes with exceptionally long lifetimes as efficient PDT PSs.Based on the heavy-atom effect, intersystem crossing of these complexes changes the excited state from singlet to atriplet state,thereby enabling singlet oxygen generation. To overcome the limitation of quenching effects in water and improve water solubility,the lead compound 3 was encapsulated in ap olymer matrix. It showed impressive phototoxicity upon irradiation at 500 nm in various monolayer cancer cells as well as 3D multicellular tumour spheroids,w ithout observed dark toxicity.advanced research and preclinical studies using the first and second generation of PSs,the translational status of PDT still remains unsatisfactory.Ideal photosensitizers must be chemically pure and stable in biological fluids while being efficient reactive oxygen species (ROS)g enerators. [1] PDT relies on the photoactivation of ap referably nontoxic PS in the presence of oxygen to create ROS. During this process,the PS is excited to asinglet state ( 1 PS) from which it undergoes intersystem crossing (ISC) to alonger-lived triplet state ( 3 PS). In at ype Im echanism, an electron or proton is transferred from or to the excited 3 PS to or from the biological environment in ap rocess that commonly involves CO 2 À , COOH, or COH radicals.I nc ontrast, in at ype II mechanism, the energy of the excited 3 PS is transferred to molecular oxygen ( 3 O 2 )t og enerate singlet oxygen ( 1 O 2 ). These species are highly reactive and can directly react with the biological surroundings to trigger cell death. Porphyrins,c hlorins,a nd pthalocyanines form the basic structure of many PSs,w hich are not only generally difficult to synthesise and to purify but can also suffer from other drawbacks,including poor aqueous solubility,a ggregation, slow clearance from the body,a nd hepatotoxicity. [2] It would therefore be of high interest to develop new PSs based on ahalf-porphyrin unit. This design would retain the excited-state properties of porphyrins while being synthetically less challenging.M oreover,t oo vercome the limitations of the current PSs,the use of metal complexes has emerged as an interesting alternative due to their attractive photophysical properties (e.g.,p hotostability,h igh 1 O 2 production), high water solubility,and chemical stability. In this field, the most well-studied transition-metal complexes are those of Ru II , [3] Os II , [4] Rh III , [4b, 5] and Ir III . [3l, 4c, 6] Such complexes have shown some extremely promising results, with one having completed phase Iclinical trial. [3c] However, the metal ions employed in these complexes are not abundant and are oft...