Antifungal Drugs Clotrimazole Research Articles

Antifungal Properties of Eucalyptus Camaldulensis Essential Oil Against Aspergillus Spp

Eucalyptus Essential oils has a variety of bioactivities as fungicidal, bactericidal, insecticidal and other therapeutic properties . This investigation was conducted to assess the antifungal properties of Eucalyptus camaldulensis essential oil alone and in combination with clotrimazole against Aspergillus spp that isolated from patients. The in laboratory results appeared that the development of Aspergillus spp was discouraged by the essential oil at all tested concentration (100 , 50 and 25%) and the effect was increased with the increasing of concentration. The antifungal drugs clotrimazole , itraconzole and griseofulvin also affect the development of Aspergillus spp and the fungus A. fumigatus was less sensitive to essential oil and drugs than the other species of Aspergillus. The outcome shown that the combination of clotrimazol with essential oil was more effective than each one alone and the combination enhanced the antifungal activity with an additive interaction.

Oxidative effects of the human antifungal drug clotrimazole on the eucaryotic model organism Saccharomyces cerevisiae.

Clotrimazole is a type of antifungal medication developed from azole compounds. It exhibits several biological actions linked to oxidative stress. This study focuses on the oxidative effects of clotrimazole on the eukaryotic model yeast, Saccharomyces cerevisiae. Our results showed that although initial nitric oxide levels were above control in clotrimazole exposed cells, they showed decreasing tendencies from the beginning of incubation and dropped below control at 125 µM from the 60th min. The highest superoxide anion and hydrogen peroxide levels were 1.95- and 2.85-folds of controls at 125 µM after 15 and 60min, respectively. Hydroxyl radical levels slightly increased throughout the incubation period in all concentrations and reached 1.3-fold of control, similarly at 110 and 125 µM in the 90th min. The highest level of reactive oxygen species was observed at 110 µM, 2.31-fold of control. Although NADH/NADPH oxidase activities showed similar tendencies for all conditions, the highest activities were found as 3.07- and 2.27-folds of control at 125 and 110 µM in the 15th and 30th min, respectively. The highest superoxide dismutase and catalase activities were 1.59- and 1.21-folds of controls at 110 µM clotrimazole in 30 and 90min, respectively. While the drug generally induced glutathione-related enzyme activities, the ratios of glutathione to oxidized glutathione were above the control only at low concentrations of the drug. The levels of lipid peroxidation in all treated cells were significantly higher than the controls. The findings crucially demonstrate that this medicine can generate serious oxidative stress in organisms.

Delayed clearance of the pro-carcinogen benzo[a]pyrene in PLHC-1 cells when co-exposed to the antifungal drug clotrimazole and effects on the CYP1A biomarker

Cytochrome P450 1 A (CYP1A) is a key enzyme in the metabolism of the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) in animals, and a biomarker for environmental PAH exposure. The common antimycotic imidazole drug clotrimazole (CLO) has been detected in the aquatic environment and likely co-exists with BaP. Like BaP, CLO can bind to CYP1A enzymes and can act as a CYP1A inhibitor. Co-exposure of BaP with CLO significantly delayed BaP elimination in a fish liver cell line (PLHC-1). Intracellular BaP concentration was 2.4 times higher after 6 h in co-exposed cells, compared to cells exposed to BaP alone. Higher BaP concentrations in cells co-exposed to CLO positively correlated with CLO dose, indicating CLO-mediated delays in BaP clearance. After 24 h, BaP was undetectable irrespective of CLO co-exposure. In contrast, intracellular CLO concentrations remained constant over the 72 h experimental period. Co-exposure of BaP with CLO caused synergistic and time-dependent increases on the CYP1A biomarker both on CYP1A mRNA levels and on CYP1A enzyme activity, in accordance with an apparent delayed BaP elimination in the presence of CLO. These results indicate a toxicokinetic interaction between BaP and CLO on the CYP1A enzyme that delays metabolic clearance of BaP.

An Efficient Antimicrobial Performance of Hybrid Functionalized MWCNTs/GNPts Bionanocomposites Based on Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)

AbstractHaloferax mediterranei archaea has been utilized to biosynthesize Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) polyester from date waste as carbon source. The produced biopolymer has been composited with different percentages (1 %, 3 %, 5 % and 10 %) of a hybrid filler based on 1 : 1 carboxylated multi‐walled carbon nanotubes (CMWCNTs) and graphene nanoplates (GNPts). The synthesized bionanocomposites PHBV/(CMWCNTs‐GNPts)(1,3,5,10%) have been characterized by FTIR, TGA, XRD, SEM and EDX. In addition, they were studied for their antibacterial properties against gram negative and gram positive strains of M. Luteus, S. Aureus, P. Aerugensa and E. Coli, and the results showed excellent antibacterial effect especially against gram negative strains of P. Aerugensa and E. Coli, showing inhibition zones of 52 % and 81 %, respectively, compared to chloramphenicol control that is used. Also, antifungal activities were investigated against G. Candidum and C. Albicans and showed that the produced bionanocomposites had inhibition zones of 32 % and 73 %, respectively, compared to the antifungal drug clotrimazole which was used as control.

Novel Chewable Gum Sticks for The Treatment of Oral Candidiasis

Beeswax is used in medicine from ancient times treatment od oral candidacies is possible by formulation of chewable gum sticks consisting natural hydrophobic wax with anti-fungal drug clotrimazole. Gum sticks are smooth and compatible in oral cavity. Develop safe stable and instant release dosage form offers opportunity for treating immune compromised patients and maintaining their good oral health.

Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. Statement of significanceA dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

In-vitro study of effect of incorporation of antifungal drugs upon growth of candida and surface hardness in permanent soft liners

Introduction: - Long term soft liners (acrylic and silicone based) are used to prevent damage to the abused mucosa, but they have the disadvantage of becoming porous with time leading to a suitable environment for opportunistic infections. This study was aimed to examine the inhibitory effect of incorporation of antifungal drug clotrimazole into long term denture soft liners on the growth of Candida albicans in vitro and evaluate the change in the surface hardness of soft liners.Materials and Method: The present study was done for two different long term soft liners, acrylic based (Permasoft) and silicone-based (Mollosil), by addition of clotrimazole drug in their minimum inhibitory concentration. The properties –zone of inhibition and surface hardness(Shore A) were evaluated at time intervals of 1,7,14,21,35 and 42days. A total of 224 samples were prepared. The properties were analyzed and inter group and intra group data was analyzed statistically by using One way ANOVA, Tukey post hoc-test and Paired t test.Result: The results showed significant creation of zone of inhibition for samples containing clotrimazole with the zone of inhibition decreasing with time. The surface hardness of all the samples increases with time.

In Vitro Antifungal Activity of of Pleurotuseryngii against Trichophytonrubrum

Biological control represents an important approach for controlling many dermatophyte fungi.Pleurotuseryngiiisa promising and effective bioagent against many pathogenic fungi. In this paperPleurotuseryngiiwere screened for their efficacy against Trichophytonrubrum. The results had been revealedthat the fruiting bodies extract of the bioagentPleurotuseryngiiaffected the radial growth of the dermatophytefungus Trichophytonrubrum. The extract of test fungus at all test concentrations had inhibitory effect on theradial growth of Trichophytonrubrum. The results had been revealed also that ethanolic extract was moreeffective than the aqueous extract of Pleurotuseryngiibut lower than the affectivity of the antifungal drugclotrimazole.

Human-relevant concentrations of the antifungal drug clotrimazole disrupt maternal and fetal steroid hormone profiles in rats

Clotrimazole is a non-prescription and broad-spectrum antifungal drug sold under brand names such as Canesten® and Lotrimin®. It is used to treat different types of fungal infections, from oral thrush to athlete's foot and vaginal mycosis. The level of exposure to clotrimazole is uncertain, as the exact usage amongst self-medicating patients is unclear. Recent studies have raised potential concern about the unsupervised use of clotrimazole during pregnancy, especially since it is a potent inhibitor of CYP enzymes of the steroidogenesis pathway. To address some of these concerns, we have assessed the effects of intrauterine exposure to clotrimazole on developing rat fetuses. By exposing pregnant rats to clotrimazole 25 or 75 mg/kg bw/day during gestation days 7–21, we obtained internal fetal concentrations close to those observed in humans. These in vivo data are in strong agreement with our physiologically-based pharmacokinetic (PBK)-modelled levels. At these doses, we observed no obvious morphological changes to the reproductive system, nor shorter male anogenital distance; a well-established morphometric marker for anti-androgenic effects in male offspring. However, steroid hormone profiles were significantly affected in both maternal and fetal plasma, in particular pronounced suppression of estrogens was seen. In fetal testes, marked up-concentration of hydroxyprogesterone was observed, which indicates a specific action on steroidogenesis. Since systemic clotrimazole is rapidly metabolized in humans, relevant exposure levels may not in itself cause adverse changes to the reproductive systems. Its capacity to significantly alter steroid hormone concentrations, however, suggests that clotrimazole should be used with caution during pregnancy.

A New Anti-Estrogen Discovery Platform Identifies FDA-Approved Imidazole Anti-Fungal Drugs as Bioactive Compounds against ERα Expressing Breast Cancer Cells.

17β-estradiol (E2) exerts its physiological effects through the estrogen receptor α (i.e., ERα). The E2:ERα signaling allows the regulation of cell proliferation. Indeed, E2 sustains the progression of ERα positive (ERα+) breast cancers (BCs). The presence of ERα at the BC diagnosis drives their therapeutic treatment with the endocrine therapy (ET), which restrains BC progression. Nonetheless, many patients develop metastatic BCs (MBC) for which a treatment is not available. Consequently, the actual challenge is to complement the drugs available to fight ERα+ primary and MBC. Here we exploited a novel anti-estrogen discovery platform to identify new Food and Drug Administration (FDA)-approved drugs inhibiting E2:ERα signaling to cell proliferation in cellular models of primary and MBC cells. We report that the anti-fungal drugs clotrimazole (Clo) and fenticonazole (Fenti) induce ERα degradation and prevent ERα transcriptional signaling and proliferation in cells modeling primary and metastatic BC. The anti-proliferative effects of Clo and Fenti occur also in 3D cancer models (i.e., tumor spheroids) and in a synergic manner with the CDK4/CDK6 inhibitors palbociclib and abemaciclib. Therefore, Clo and Fenti behave as “anti-estrogens”-like drugs. Remarkably, the present “anti-estrogen” discovery platform represents a valuable method to rapidly identify bioactive compounds with anti-estrogenic activity.

Graphene oxide as a functional excipient in buccal films for delivery of clotrimazole: Effect of molecular interactions on drug release and antifungal activity in vitro.

Graphene oxide (GO) is an amphiphilic, high surface area material with great potential as a functional excipient in drug delivery. The present study aimed at incorporating GO in buccal polyelectrolyte films for delivery of antifungal drugs and investigating the effect of GO on the film properties and drug release profiles, as well as antifungal activities. Mucoadhesive excipients chitosan and alginate were selected to form polyelectrolyte films with the antifungal drug clotrimazole. The buccal formulations were prepared by mixing the excipients and clotrimazole via probe sonication, followed by film casting and drying. Inclusion of GO in the formulations increased clotrimazole release from the films in vitro (pH 6.8), possibly due to GO altering the electrostatic interactions between chitosan and alginate. An increase of in vitro activity against Candida albicans was observed when 0.04wt% GO was added in the formulation containing clotrimazole. However, when the GO amount increased to 0.09wt%, the films had similar antifungal ability to the films with 0.04wt% GO, suggesting that the electrostatic and hydrophobic interactions between GO and clotrimazole also affects the antifungal effect of clotrimazole. In summary, GO has a great potential as a functional excipient for delivery of antifungal drugs.

Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa.

The long-term use of antibiotics has led to the emergence of multidrug-resistant bacteria. A promising strategy to combat bacterial infections aims at hampering their adaptability to the host environment without affecting growth. In this context, the intercellular communication system quorum sensing (QS), which controls virulence factor production and biofilm formation in diverse human pathogens, is considered an ideal target. Here, we describe the identification of new inhibitors of the pqs QS system of the human pathogen Pseudomonas aeruginosa by screening a library of 1,600 U.S. Food and Drug Administration-approved drugs. Phenotypic characterization of ad hoc engineered strains and in silico molecular docking demonstrated that the antifungal drugs clotrimazole and miconazole, as well as an antibacterial compound active against Gram-positive pathogens, clofoctol, inhibit the pqs system, probably by targeting the transcriptional regulator PqsR. The most active inhibitor, clofoctol, specifically inhibited the expression of pqs-controlled virulence traits in P. aeruginosa, such as pyocyanin production, swarming motility, biofilm formation, and expression of genes involved in siderophore production. Moreover, clofoctol protected Galleria mellonella larvae from P. aeruginosa infection and inhibited the pqs QS system in P. aeruginosa isolates from cystic fibrosis patients. Notably, clofoctol is already approved for clinical treatment of pulmonary infections caused by Gram-positive bacterial pathogens; hence, this drug has considerable clinical potential as an antivirulence agent for the treatment of P. aeruginosa lung infections.

Isolation, speciation and antifungal susceptibility testing of Candida isolates from various clinical specimens at a tertiary care hospital, Nepal

BackgroundCandida species are responsible for various clinical infections ranging from mucocutaneous infection to life threatening invasive diseases along with increased resistance to antifungal drugs has made a serious concern. Resistance to antifungal agents has increased during the last decade. Thus, identification of Candida up to species level and its antifungal susceptibility testing has a paramount significance in the management of Candidal infections. The aim of the study was to speciate Candida species and to determine antifungal susceptibility pattern of Candida species to antifungal agents.MethodsA total of 100 consecutive Candida species were isolated from 1248 clinical specimens over 7 months period. Growths on Sabouraud dextrose agar were evaluated for colony appearance, macroscopic examination, Gram staining, germ tube test and urea hydrolysis test. Further, they were processed for Candida speciation on CHROMagar. Antifungal susceptibility testing was performed as recommended by Clinical and Laboratory Standards Institute (CLSI) M44-A document.ResultsOut of 100 Candida isolates, Candida albicans (56%) was the most common species. Among the non-albicans Candida species, Candida tropicalis (20%) was the predominant isolate followed by Candida glabrata (14%). Regarding antifungal susceptibility pattern, Candida species were more susceptible to clotrimazole (82%) followed by fluconazole (64%) and miconazole (44%).ConclusionsCandida albicans was the predominant species responsible for various Candidal infections. Among commonly used antifungal drugs clotrimazole, miconazole and fluconazole were most effective.

Spectrophotometric and spectroscopic studies on charge transfer complexes of the antifungal drug clotrimazole

Clotrimazole (CLZ) is an imidazole derivative that is therapeutically used as an antifungal drug. The routine control analysis of CLZ requires rapid, reliable, accurate and precise methods for the quantification of the drug in its pharmaceutical formulations. Spectrophotometric methods are presented for the determination of the antifungal agent that are based on the charge transfer complexation reaction of CLZ with the π-acceptors tetracyanoethylene (TCE) and 7,7′,8,8′-tetracyanoquinodimethane (TCNQ). The formation of coloured complexes was quantitated at 396nm and 842nm for CLZ-TCE and CLZ-TCNQ, respectively, which enabled the development of simple and accurate spectrophotometric methods for the analysis of CLZ in pure drug substances and its pharmaceutical products. Under the optimum reaction conditions, linear relationships with appreciable correlation coefficients (0.9985–0.9994) were found between the absorbance at the relevant maxima and the concentrations of CLZ in the range of 5.00–35.00μgmL−1 for CLZ-TCE and 1.00–25.00μgmL−1 for CLZ-TCNQ. The molar absorptivities and Sandell's sensitivity values were also statistically evaluated. The proposed methods were successfully applied to analyze CLZ in topical creams and sterile solutions with mean recovery percentages in the range of 99.60–100.20%, which indicated no interference from the inactive ingredients. Furthermore, the charge transfer complexes of CLZ were also characterized by FT-IR spectroscopy.

Expeditious Entry to Functionalized Pseudo-peptidic Organoselenide Redox Modulators via Sequential Ugi/SN Methodology.

An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.

Further Evidence of an Alternative Ion Permeation Pathway in the Nociceptor TRPM3

TRPM3 is a member of the melastatin family of the transient receptor potential (TRP) channels and was described as a nociceptor. It can be activated by a multitude of stimuli, including chemical compounds such as pregnenolone sulphate (PS) or nifedipine (Nif), as well as by physical signals like temperature. Activation of TRPM3 by all these different type of stimuli leads to the opening of a central pore that is formed by the transmembrane domains five (S5) and six (S6) and the interconnecting pore-loop, resulting in an outward rectifying current-voltage relationship. Recently, we have described the existence of an alternative ion permeation pathway in TRPM3. This alternative pathway could be opened by simultaneous application of PS and the antifungal drug clotrimazole (Clt), resulting in a current shape that showed an in- and outward rectification. Very recently, we have described a novel synthetic agonist of TRPM3, CIM0216, which is remarkable by the fact that it is able to open as single compound both, the central pore and the alternative ion permeation pathway.By the use of CIM0216, we were able to further investigate the biophysical properties of the alternative ion permeation pathway and to achieve further evidence of the existence of an alternative ion permeation pathway in TRPM3. In addition, new mutagenesis studies of TRPM3 provided further evidence for the location of the alternative ion permeation pathway within the region of S4 of the voltage sensing domain.All together, these data provide more evidence for the existence of an alternative ion permeation pathway in TRPM3 that will open upon displacement of the voltage sensing domain S4.

An Alternative Ion Permeation Pathway in the TRPM3α1 Isoform?

TRPM3 is a cation conducting ion channel that belongs to the superfamily of transient receptor potential (TRP) channels. It is polymodally regulated by stimuli including heat, hypoosmolarity, the endogenous agonist pregnenolone sulphate (PS) as well as the synthetic agonist nifedipine. Recently, we have shown that combined application of PS and the antifungal drug clotrimazole (Clt) leads to the activation of TRPM3 by inducing the opening of two pores, the central pore and an alternative ion permeation pathway. We have further identified a selective activator of TRPM3, CIM0216, which is able to open both pathways independently of the presence of other chemicals. At the moment a tremendous amount of TRPM3 splice variants have been described. In this study, we have selected one splice variant TRPM3α1, that differs from the TRPM3α2 isoform only in the presumed pore region. Remarkably, the TRPM3α1 isoform did not show any increase in channel activity during stimulation by PS or nifedipine. However, HEK293 cells transfected by TRPM3α1 showed a robust increase in current amplitude during stimulation by CIM0216. Here, we have further investigated the existence of an alternative ion permeation pathway in the TRPM3α1 isoform. This study aims to understand the mechanism of activation of the alternative ion permeation pathway in TRPM3 and to determine the necessary structural features to open the alternative pathway.

Formulation and Evaluation of Proniosome Based Drug Delivery System of the Antifungal Drug Clotrimazole

In the present study proniosomal gel of clotrimazole was formulated by using lecithin, cholesterol as encapsulating agents, nonionic surfactants Span and Tween with different grades. Evaluation of proniosomal gels for pH, vesicle size analysis, encapsulation efficiency, drug diffusion profiles, ex-vivo skin permeation and ex-vivo drug deposition studies on guinea pig skin, irritation test on rabbit and stability studies was performed. The preliminary compatibility studies revealed that there were no interactions between clotrimazole and excipients which was evident from FTIR and DSC studies. The physical characteristics of proniosomal gels were found to be within the acceptable limits. The vesicle size was found to be in the range 5.25-15.23μm. The proniosomes were spherical and homogenous in structure when observed under optical microscopy. The ex-vivo skin permeation and ex-vivo drug deposition studies showed the drug release from formulations F3, F4 and marketed formulation was 48.60%, 36.9% and 27.48 % respectively and the percent of clotrimazole deposited in skin after 24 h was found to be 35.7%, 43.6% and 15.17% for formulation F3, F4 and marketed formulation respectively. The release from the proniosomal gel was prolonged when compared to conventional formulation and showed a two fold increase in the drug deposition in the skin compared to conventional cream. No obvious erythema, edema or inflammation was observed on rabbits’ skin after one week of application of the selected formulation. Results of antifungal studies revealed that the developed proniosomal gel is more efficient when compared with the marketed formulation. The stability studies showed that proniosomal gels were stable at 5±3°C and 25±2°C. The above results indicated that the proniosomal gels of clotrimazole could be formulated for sustained release.

In vitro activity of antifungal drugs against Plasmodium falciparum field isolates

The increasing resistance of the malaria parasite Plasmodium falciparum to currently available drugs necessitates a continuous effort to develop new antimalarial agents. We therefore aimed to assess the in vitro activity of the antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole, flucytosine, amphotericin B, and caspofungin against field isolates of P. falciparum from Lambaréné, Gabon. Using the histidin-rich protein 2 (HRP-2) assay we determined the drug susceptibility (EC(50), EC(90)) of 16 field isolates obtained from outpatients attending the Albert Schweitzer Hospital in Lambaréné, Gabon. For fluconazole, itraconazole and caspofungin the in vitro growth inhibition of these drugs is reported for the first time. Our data indicate that clotrimazole, fluconazole, itraconazole and caspofungin show median EC(50) values of 3.1 µg/mL, 1.9 µg/mL, 1.1 µg/mL and 1.1 µg/mL respectively. Ketoconazole, voriconazole, flucytosine and amphotercin B showed no relevant growth inhibition within the range of drug concentrations used in this study.

Clotrimazole as an amplifier of hemin-induced damage to human erythrocytes. Antioxidant-independent protective effects of flavonoids

This study is focused on the effect of the antifungal drug clotrimazole (CLT), also possessing anti-malarial and anticancer activities, on hemin-induced hemolysis and changes in ion permeability and filter-ability of human erythrocytes. In the presence of 10 μM clotrimazole, the hemolytic response of erythrocytes to exogenous hemin at concentrations as low as 2–8 μM was considerably potentiated and their filterability, as measured by passing them through a 5-μm nuclepore filter, dropped sharply. Flavonoids quercetin (Q) and taxifolin (DHQ), unlike the standard antioxidant Trolox, abolished the effects of clotrimazole, suggesting that protection of hemin-treated erythrocytes by flavonoids is not related to their antioxidant properties.