Identification of antimycobacterial 8-hydroxyquinoline derivatives as in vitro enzymatic inhibitors of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase.

The increasing prevalence of drug-resistant Mycobacterium tuberculosis strains stimulates the discovery of new drug candidates. Among them are 8-hydroxyquinoline (8HQ) derivatives that exhibited antimicrobial properties. Unfortunately, there is a lack of data assessing possible targets for this class mainly against Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (MtInhA), a validated target in this field.

Synergistic activity of clioquinol with voriconazole and amphotericin B against fungi of interest in eye infections.

Keratoplasty represents a risk factor for fungal eye infections, despites the antibacterial actives in the corneal tissue preservation means, it does not contain active substances with antifungal action. Among the most commonly associated fungal agents are the species belonging to the genera Fusarium and Candida. These agents can trigger an infectious process characterized by swift progression associated with high rates of morbidity, causing irreversible damage.

In silico and in vitro analysis of the mechanisms of action of nitroxoline against some medically important opportunistic fungi.

The increasing resistance to antifungal agents associated with toxicity and interactions turns therapeutic management of fungal infections difficult. This scenario emphasizes the importance of drug repositioning, such as nitroxoline - a urinary antibacterial agent that has shown potential antifungal activity. The aims of this study were to discover the possible therapeutic targets of nitroxoline using an in silico approach, and to determine the in vitro antifungal activity of the drug against the fungal cell wall and cytoplasmic membrane.

Antimicrobial activity of clioquinol and nitroxoline: a scoping review.

Clioquinol and nitroxoline, two drugs with numerous pharmacological properties fallen into disuse for many decades. The first was considered dangerous due to contraindications and the second mainly because was taken as ineffective, despite its known antibacterial activity. In the last decades, the advances in pharmaceutical chemistry, molecular biology, toxicology and genetics allowed to better understand the cellular action of these compounds, some toxicological issues and/or activity scopes.

Iron chelation and inhibition of metallopeptidases mediate anti-Trichomonas vaginalis activity by a novel 8-hydroxyquinoline derivative.

Trichomoniasis is a neglected parasitic infection, with no oral therapeutic alternatives to overcome the pitfalls of currently approved drugs. In this context, the search for new anti-Trichomonas vaginalis drugs is imperative. Here we report the selective anti-T.

A chloroacetamide derivative as a potent candidate for fusariosis treatment.

Fusariosis has presented a significant increase in their incidence in the last years. This epidemiological panorama probably is due to the increasing profile of refractory susceptibility of Fusarium spp. to available drugs, especially in immunocompromised individuals.

8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for biofilm in haemodialysis devices.

The presence of biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti- activity.

Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis.

Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis.

Limonene and Perillyl Alcohol Derivatives: Synthesis and Anticancer Activity.

Limonene and perillyl alcohol are natural monoterpenes that have attracted the attention of medicinal chemists due to their promising anticancer activities. Considering this, both compounds were explored as scaffolds to obtain various derivatives with anticancer activity. In this review, the data are organized for the first time, with a focus on the synthetic methods and strategies to obtain the derivatives throughout the period from 2000 to 2020.

potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment.

Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed.

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis.

Fungal infections have emerged as a current serious global public health problem. The main problem involving these infections is the expansion of multidrug resistance. Therefore, the prospection of new compounds with efficacy antifungal becomes necessary.

8-Hydroxyquinoline 1,2,3-triazole derivatives with promising and selective antifungal activity.

Fungal infections that affect humans and plants have increased significantly in recent decades. However, these pathogens are still neglected when compared to other infectious agents. Due to the high prevalence of these infections, the need for new molecules with antifungal potential is recognized, as pathogenic species are developing resistance to the main drugs available.

Synergistic association of clioquinol with antifungal drugs against biofilm forms of clinical Fusarium isolates.

Background: The influence of biofilm on the complexity of fungal diseases has been reported in recent years, especially in non-invasive mycoses such as keratitis and onychomycosis. The difficulty in treating cases of fusariosis in the human medical clinic exemplifies this situation, because when Fusarium spp. are present in the form of biofilm, the permeation of antifungal agents is compromised.

In vitro pharmacokinetics/pharmacodynamics modeling and efficacy against systemic candidiasis in Drosophila melanogaster of a bisaryloxypropanamine derivative.

The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling.

Rational selection of antifungal drugs to propose a new formulation strategy to control Candida biofilm formation on venous catheters.

Introduction: Infections associated with medical devices are often related to colonization by Candida spp. biofilm; in this way, numerous strategies have been developed and studied, mainly in order to prevent this type of fungal growth.

Aim: Considering the above, the main objective of the present study is to make a rational choice of the best antifungal therapy for the in vitro treatment of the biofilm on venous catheters, proposing an innovative formulation of a film-forming system to coat the surface in order to prevent the formation of biofilms.

Design, synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens.

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria.

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride.

Background: Fungal infections are highly prevalent and are responsible for high rates of morbidity and mortality. In this context, the search for new treatment alternatives is very relevant.

Objectives: Analyse chemical compounds for antifungal potential against dermatomycosis fungi.

New insights into the mechanism of antifungal action of 8-hydroxyquinolines.

The 8-hydroxyquinoline core is a privileged scaffold for drug design explored to afford novel derivatives endowed with biological activity. Our research aimed at clarifying the antifungal mechanism of action of clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid (three 8-hydroxyquinoline derivatives). The antifungal mode of action of these derivatives on spp.

Oral clioquinol is effective in the treatment of a fly model of Candida systemic infection.

Background: Clioquinol was used in the 1950s-1970s as antimicrobial but its oral formulations were withdrawn from the market due to suspected neurotoxicity. Currently, there is possibility of repositioning of oral clioquinol formulations.

Objectives: To evaluate the antifungal activity and toxicological parameters of clioquinol and the other two 8-hydroxyquinoline derivatives using alternative animal models and to study the interaction dynamic of clioquinol with Candida albicans.

Rapid tools to gain insights into the interaction dynamics of new 8-hydroxyquinolines with few fungal lines.

The combination of tools such as time-kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8-hydroxy-5-quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability.

Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices.

Purpose: Candida biofilm infections are frequently linked to the use of biomaterials and are of clinical significance because they are commonly resistant to antifungals. Clioquinol is an antiseptic drug and is effective against multidrug-resistant Candida. We investigated the effect of clioquinol and two other 8-hydroxyquinoline derivatives on Candida biofilm.

Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design.

Clioquinol is an 8-hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti-Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8-hydroxyquinoline derivatives (8-hydroxy-5-quinolinesulfonic acid and 8-hydroxy-7-iodo-5-quinolinesulfonic acid).

Synthesis and antimicrobial activity of 6-triazolo-6-deoxy eugenol glucosides.

A new series of 1,2,3-triazole eugenol glucosides were synthesized. The new compound structures were confirmed by MS, (1)H NMR and (13)C NMR. All of the synthesized compounds were screened for antimicrobial and cytotoxic activity.

New insights into the chemistry and antioxidant activity of coumarins.

Coumarins are considered to be privileged structures due to their broad range of biological properties, including anticoagulant, anti-neurodegenerative, antioxidant, anticancer and antimicrobial activities. These interesting properties of coumarins can be ascribed to the chemical attributes of the 2H-chromen-2-one core; its aromatic ring can establish a series of hydrophobic, π-π, CH-π and cation-π interactions, and the two oxygen atoms in the lactone ring may hydrogen-bond to a series of amino acid residues in different classes of enzymes and receptors. Additionally, the double bond in the lactone helps to make the entire system planar, allows charge delocalization between the carbonyl group of the lactone and the aromatic ring and confers the characteristic fluorescence of this class of compounds, which can be explained by their preventing the trans-cis transformation of the double bond under ultraviolet (UV) irradiation.

Synthesis and evaluation of D-gluconamides as green mineral scales.

A series of 13 D-gluconamides were synthesized in moderate to good yields and evaluated as green scale inhibitors. The crystal structures of two compounds were determined by X-ray crystallography. The compounds 6c and 6d showed a reasonable inhibition of BaSO(4) precipitation from aqueous solution (47% and 51%, respectively) that indicated the potential for these derivatives of δ-gluconolactone.