Bioorganometallic Compounds as Novel Drug Targets against Schistosomiasis in Sub-Saharan Africa: An alternative to Praziquantel?

Abstract

Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, Praziquantel, which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance.

Uncommon Haemorrhagic Cystitis of Infectious Origin: A Narrative Review for Urologists

“… 71 Reports of decreased PZQ sensitivity in some Schistosoma spp. strains are concerning; 72 however, new therapeutic strategies are in development. 72 , 74 , 75 …”

“…71 Treatment Praziquantel (PZQ) is considered the best available drug for schistosomiasis although its mechanism of action is not fully understood. 71,72 In the absence of standardized regimen, a single-day, oral dose of 40 mg/kg of PZQ is indicated by most authors as safe and effective for all Schistosoma spp, either in one or divided in two administrations, 71 with a reported cure rate of 77.1% for S. haematobium. 73 No correlation between cure rates and dosage of PZQ has been described for S. hematobium, 73 how-ever, especially in low-burden settings, higher dosages (up to 80 mg/kg), or a second PZQ dose after 15 days from the first, have been safely and effectively used.…”

Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica

“…The large-scale and mono-therapeutic use of PZQ has raised many concerns for the treatment and control of schistosomiasis. The concerns mainly focused on the lack of activity against immature schistosome and the growing inclination to resistance of PZQ, which could be explanations to the poor cure rates and treatment failures in residents of high-risk regions [ 30 ]. Thus, it is of increasing importance to develop new drugs in the face of potential resistance to PZQ for the treatment of schistosomiasis, and the absence of an effective vaccine [ 31 ].…”

LigandDiff: de Novo Ligand Design for 3D Transition Metal Complexes with Diffusion Models

“…Metallodrugs open different and unique pathways for disease treatment, which traditional organic drugs cannot achieve due to drug resistance. 18 In addition, organometallic complexes also have a wide range of applications in materials, like solar cells, 19 electrocatalysts, 20 batteries, 21 etc. Given the great importance of organometallic complexes in both medical and industrial applications, much attention has been paid to the design of new organometallic complexes.…”

“…In both cases, the metal is the focus of the metallodrug and tunes the 3D shape of the small organic ligands attached to the metal center. Metallodrugs open different and unique pathways for disease treatment, which traditional organic drugs cannot achieve due to drug resistance . In addition, organometallic complexes also have a wide range of applications in materials, like solar cells, electrocatalysts, batteries, etc.…”