Flavonoid Complexes as Promising Anticancer Metallodrugs

Flavonoid metal complexes commonly exhibit an improvement of biological activity compared to the parent ligands. This chapter is focused on the antioxidant and anticanc-cer properties of flavonoid metal complexes, in correlation with their binding ability to vital macromolecules such as nucleic acids and serum proteins. Perspectives for an adequate formulation of these complexes were also discussed

Nanoformulation as a Tool for Improve the Pharmacological Profile of Platinum and Ruthenium Anticancer Drugs

Cisplatin and analogs are used for the treatment of some type of cancers in combination with organic cytostatics. Also, two ruthenium (III) complexes are in clinical trials as anticancer drugs. In order to overcome toxicity and resistance associated with this therapy and/or enhance stability, a large variety of formulations based on organic, inorganic, or hybrid matrix were developed and tested both in vivo and in vitro. The best results were obtained for systems properly functionalized in order to enhance the metal content and/or to specific target the tumor tissue through overexpressed receptors

The binding properties of some novel ruthenium (III) complexes with human serum transferrin

Aim. The transferrin cycle gained increased interest in recent years and it holds promise as an attractive system for strategies of drug targeting to tumors. Neoplasic cells exhibit a large demand of iron and therefore express highly transferrin receptors. As a consequence, transferrin conjugates can preferentially interact with cancer cells. This strategy is exploited nowadays for targeting novel anti-cancer drugs. Recent data showed that ruthenium (III) compounds possess antitumor and antimetastatic effects, due to their affinity for crucial biomolecules (like transferrin). Methods. The paper presents the transferrin-binding properties of some novel ruthenium (III) complexes with general formula RuL2 (DMSO) mCl3 ·nH2O ((Ru-nf) L: norfloxacin (nf), m = 1, n = 1; (Ru-cpx) L: ciprofloxacin (cpx), m = 2, n = 2; (Ru-oflo) L: ofloxacin (oflo), m = 1, n = 1; (Ru-levo) L: levofloxacin (Levo), m = 2, n = 8; (Ru-pip) L: pipemidic acid (pip), m = 1, n = 2, DMSO: dimethylsulfoxide). We investigated, in vitro, the interactions of these ligands with human transferrin through spectroscopic techniques, with the ultimate goal of preparing adducts with good selectivity for cancer cells. Results. All studied complexes interact with human serum transferrin; the molar ratio [complex]/[transferrin] strongly influences the binding affinity. Conclusions. The best interaction between the complexes studied and transferrin is achieved for a molar ratio of 8; the best interaction was registered for Ru-pip, followed by Ru-nf. Keywords: ruthenium (III) complexes, transferrin.Мета. Останніми роками трансфериновий цикл викликає по - силений інтерес як перспективна система цільової доставки протипухлинних препаратів безпосередньо в пухлину. Неопластичні клітини потребують багато заліза, через що експресують велику кількість трансферинових рецепторів. Внаслідок цього кон ’югати трансферину здатні насамперед взаємодіяти з раковими клітинами. Цю стратегію у наш час використовують для пошуку нових протиракових препаратів. Останні дані демонструють, що сполукам рутенію (III) притаманні протипухлинні і антиметастатичні ефекти завдяки їхній афінності до важливих біомолекул (таких як трансферин). Методи. У статті представлено трансферин-зв’язувальні властивості деяких нових комплексів рутенію (III) загальною формулою RuL2 (DMSO) mCl3 ×nH2O ((Ru-nf) L: норфлоксацин (nf), m = 1, n = = 1; (Ru-cpx) L: ципрофлоксацин (cpx), m = 2, n = 2; (Ru-of) L: офлоксацин (oflo), m = 1, n = 1; (Ru-levo) L: левофлоксацин (Levo), m = 2, n = 8; (Ru-pip) L: піпемідинова кислота (pip), m = = 1, n = 2, DMSO: диметилсульфоксид). Ми вивчали взаємодію in vitro цих лігандів з трансферином людини методом спектроскопії для одержання адуктів з високою селективністю до ракових клітин. Результати і висновки. Всі досліджувані комплекси взаємодіють з сироватковим трансферином людини, молярне співвідношення [комплекс]/[трансферин] значно впливає на зв’язувальні властивості. Найкращу взаємодію між аналізованими комплексами і трансферином відмічено при молярному співвідношенні 8:1, а також для Ru-pip і Ru-nf. Ключові слова: комплекси рутенію (III), трансферин.Цель. В последние годы трансферриновый цикл вызывает повышенный интерес как перспективная система целевой доставки противоопухолевых препаратов непосредственно в опухоль. Неопластические клетки испытывают высокую потребность в железе и, следовательно, экспрессируют много трансферриновых рецепторов. Вследствие этого конъюгаты трансферрина способны преимущественно взаимодействовать с раковыми клетками. Эту стратегию в настоящее время используют для поиска новых противораковых препаратов. Последние данные показывают, что соединения рутения (III) обладают противоопухолевым и антиметастатическим эффектами благодаря их аффинности к важным биомолекулам (таким как трансферрин). Методы. В статье представлены трансферрин-связывающие свойства некоторых новых комплексов рутения (III) с общей формулой RuL2 (DMSO) mCl3 ×nH2O ((Ru-nf) L: норфлоксацин (nf), m = 1, n = 1; (Ru-cpx) L: ципрофлоксацин (cpx), m = 2, n = 2; (Ru-of) L: офлоксацин (oflo), m = 1, n = 1; (Ru-levo) L: левофлоксацин (Levo), m = 2, n = 8; (Ru-pip) L: пипемидиновая кислота (pip), m = 1, n = 2, DMSO: диметилсульфоксид). Мы изучили взаимодействие in vitro этих лигандов с человеческим трансферрином методом спектроскопии для получения аддуктов, обладающих хорошей селективностью к раковым клеткам. Результаты и выводы. Все исследуемые комплексы взаимодействуют с человеческим сывороточным трансферрином, молярное соотношение [комплекс]/ [трансферрин] сильно влияет на связывающие свойства. Наилучшее взаимодействие между изучаемыми комплексами и трансферрином отмечено при молярном соотношении 8:1, а также для Ru-pip и Ru-nf. Ключевые слова: комплексы рутения (III), трансферрин

Diastereomeric bactericidal effect of Ru(phenanthroline)(2)dipyridophenazine

Metal susceptibility assays and spot plating were used to investigate the antimicrobial activity of enantiopure [Ru(phen)(2)dppz](2+) (phen =1,10-phenanthroline and dppz = dipyrido[3,2-a:2 ',3 '-c]phenazine) and [-bidppz(phen)(4)Ru-2](4+) (bidppz =11,11 '-bis(dipyrido[3,2-a:2 ',3 '-c]phenazinyl)), on Gram-negative Escherichia coli and Gram-positive Bacillus subtilis as bacterial models. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for both complexes: while [-bidppz(phen)(4)Ru-2](4+) only showed a bactericidal effect at the highest concentrations tested, the antimicrobial activity of [Ru(phen)(2)dppz](2+) against B. subtilis was comparable to that of tetracyline. In addition, the -enantiomer of [Ru(phen)(2)dppz](2+) showed a 2-fold higher bacteriostatic and bactericidal effect compared to the -enantiomer. This was in accordance with the enantiomers relative binding affinity for DNA, thus strongly indicating DNA binding as the mode of action

molecules Metal Complexes of Quinolone Antibiotics and Their Applications: An Update

Abstract: Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones

Ruthenium Complexes in the Fight against Pathogenic Microorganisms. An Extensive Review

The widespread use of antibiotics has resulted in the emergence of drug-resistant populations of microorganisms. Clearly, one can see the need to develop new, more effective, antimicrobial agents that go beyond the explored ‘chemical space’. In this regard, their unique modes of action (e.g., reactive oxygen species (ROS) generation, redox activation, ligand exchange, depletion of substrates involved in vital cellular processes) render metal complexes as promising drug candidates. Several Ru (II/III) complexes have been included in, or are currently undergoing, clinical trials as anticancer agents. Based on the in-depth knowledge of their chemical properties and biological behavior, the interest in developing new ruthenium compounds as antibiotic, antifungal, antiparasitic, or antiviral drugs has risen. This review will discuss the advantages and disadvantages of Ru (II/III) frameworks as antimicrobial agents. Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru (II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix

Every year, more Cu(II) complexes are proven to be biologically active species, but very few are developed as drugs or entered in clinical trials. This is due to their poor water solubility and lipophilicity, low stability as well as in vivo inactivation. The possibility to improve their pharmacological and/or oral administration profile by incorporation into inorganic or organic matrix was studied. Most of them are either physically encapsulated or conjugated to the matrix via a moiety able to coordinate Cu(II). As a result, a large variety of species were developed as delivery carriers. The organic carriers include liposomes, synthetic or natural polymers or dendrimers, while the inorganic ones are based on carbon nanotubes, hydrotalcite and silica. Some hybrid organic-inorganic materials based on alginate-carbonate, gold-PEG and magnetic mesoporous silica-Schiff base were also developed for this purpose

Bucureºti) ♦ 61♦ Nr

A new and rapid synthesis method of azole aminals is described. Starting from pyrazole

Quinolone Complexes with Lanthanide Ions: An Insight into their Analytical Applications and Biological Activity

Quinolones comprise a series of synthetic bactericidal agents with a broad spectrum of activity and good bioavailability. An important feature of these molecules is their capacity to bind metal ions in complexes with relevant biological and analytical applications. Interestingly, lanthanide ions possess extremely attractive properties that result from the behavior of the internal 4f electrons, behavior which is not lost upon ionization, nor after coordination. Subsequently, a more detailed discussion about metal complexes of quinolones with lanthanide ions in terms of chemical and biological properties is made. These complexes present a series of characteristics, such as narrow and highly structured emission bands; large gaps between absorption and emission wavelengths (Stokes shifts); and long excited-state lifetimes, which render them suitable for highly sensitive and selective analytical methods of quantitation. Moreover, quinolones have been widely prescribed in both human and animal treatments, which has led to an increase in their impact on the environment, and therefore to a growing interest in the development of new methods for their quantitative determination. Therefore, analytical applications for the quantitative determination of quinolones, lanthanide and miscellaneous ions and nucleic acids, along with other applications, are reviewed here