Insight into Recent Drug Discoveries against Trypanosomatids and Plasmodium spp Parasites: New Metal-based Compounds

: Scaffolds of metal-based compounds can act as pharmacophore groups in several ligands to treat various diseases, including tropical infectious diseases (TID). In this review article, we investigate the contribution of these moieties to medicinal inorganic chemistry in the last seven years against TID, including American trypanosomiasis (Chagas disease), human African trypanosomiasis (HAT, sleeping sickness), leishmania, and malaria. The most potent metal-based complexes are displayed and highlighted in figures, tables and graphics; according to their pharmacological activities (IC50 > 10µM) against Trypanosomatids and Plasmodium spp parasites. We highlight the current progresses and viewpoints of these metal-based complexes, with a specific focus on drug discovery.

Evaluation of the In Vitro and In Vivo Efficacy of Ruthenium Polypyridyl Compounds against Breast Cancer

The clinical success of cisplatin, carboplatin, and oxaliplatin has sparked the interest of medicinal inorganic chemistry to synthesize and study compounds with non-platinum metal centers. Despite Ru(II)–polypyridyl complexes being widely studied and well established for their antitumor properties, there are not enough in vivo studies to establish the potentiality of this type of compound. Therefore, we report to the best of our knowledge the first in vivo study of Ru(II)–polypyridyl complexes against breast cancer with promising results. In order to conduct our study, we used MCF7 zebrafish xenografts and ruthenium complexes [Ru(bipy)2(C12H8N6-N,N)][CF3SO3]2Ru1 and [{Ru(bipy)2}2(μ-C12H8N6-N,N)][CF3SO3]4Ru2, which were recently developed by our group. Ru1 and Ru2 reduced the tumor size by an average of 30% without causing significant signs of lethality when administered at low doses of 1.25 mg·L−1. Moreover, the in vitro selectivity results were confirmed in vivo against MCF7 breast cancer cells. Surprisingly, this work suggests that both the mono- and the dinuclear Ru(II)–polypyridyl compounds have in vivo potential against breast cancer, since there were no significant differences between both treatments, highlighting Ru1 and Ru2 as promising chemotherapy agents in breast cancer therapy.

Medicinal inorganic chemistry: an updated review on the status of metallodrugs and prominent metallodrug candidates

Metallodrugs correspond to a small portion of all available drugs in the market and, yet, some of them are among the most used and important drugs in modern medicine. However, medicinal inorganic chemistry remains an underestimated area within medicinal chemistry and the main reason is the mislead association of metals to toxic agents. Thus, in this review, the potential of medicinal inorganic chemistry in drug designing is highlighted through a description of the current status of metallodrugs and metallodrug candidates in advanced clinical trials. The broad spectrum of application of metal-based drugs in medicine for both therapy and diagnosis is addressed by the extensive list of examples presented herein.

Multifunctional compounds for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia, and the prevalence of this currently untreatable disease is expected to rise in step with increased global life expectancy. AD is a multifaceted disorder commonly characterized by extracellular amyloid–beta (Aβ) aggregates, oxidative stress, metal ion dysregulation, and intracellular neurofibrillary tangles. This review will focus on medicinal inorganic chemistry strategies to target AD, with a focus on the Aβ peptide and its relation to metal ion dysregulation and oxidative stress. Multifunctional compounds designed to target multiple disease processes have emerged as promising therapeutic options, and recent reports detailing multifunctional metal-binding compounds, as well as discrete metal complexes, will be discussed.

Metal ion size profoundly affects H3glyox chelate chemistry

The bisoxine hexadentate chelating ligand, H3glyox was investigated for its affinity for Mn2+, Cu2+ and Lu3+ ions; all three metal ions are relevant with applications in nuclear medicine and medicinal inorganic chemistry.

NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry

NAMI-A ((ImH)[trans-RuCl4(dmso-S)(Im)], Im = imidazole) and KP1019/1339 (KP1019 = (IndH)[trans-RuCl4(Ind)2], Ind = indazole; KP1339 = Na[trans-RuCl4(Ind)2]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates. This has led to a considerable amount of studies on their respective chemico-biological features and to the eventual admission of both to clinical trials. The encouraging pharmacological performances qualified KP1019 mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers, whereas the non-cytotoxic NAMI-A has gained the reputation of being a very effective antimetastatic drug. A critical and strictly comparative analysis of the studies conducted so far on NAMI-A and KP1019 allows us to define the state of the art of these experimental ruthenium drugs in terms of the respective pharmacological profiles and potential clinical applications, and to gain some insight into the inherent molecular mechanisms. Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium complexes form an exemplary and unique case in the field of medicinal inorganic chemistry.