Imidazole Drugs Research Articles

Eutectic binary phase diagram and kinetically stable homogeneous co-amorphous mixtures of two imidazole drugs

Eutectic binary phase diagram and kinetically stable homogeneous co-amorphous mixtures of two imidazole drugs

Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis: analysis of the FDA Adverse Event Reporting System

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

Species distribution and antifungal susceptibility profiles of yeasts isolated from onychomycosis: a cross-sectional study with insights into emerging species.

Candida onychomycosis is a common fungal infection affecting the nails, primarily caused by Candida (C.) species. Regarding the increasing trend of Candida onychomycosis and the antifungal resistant phenomenon in recent years, this study aims to evaluate the epidemiological characteristics of Candida onychomycosis, the distribution of emerging species, and the antifungal susceptibility profiles of isolates. Onychomycosis caused by yeast species was confirmed through direct examination and culture of nail scraping among all individuals suspected to have onychomycosis and referred to a medical mycology laboratory between June 2019 and March 2022. Species of yeast isolates were identified using the multiplex PCR and PCR-RFLP methods. The antifungal susceptibility of isolates to common antifungal agents and imidazole drugs was evaluated according to the M-27-A3 CLSI protocol. Among 101 yeast strains isolated from onychomycosis, Candida parapsilosis complex (50.49%) was the most common species, followed by C. albicans (20.79%) and C. tropicalis (10.89%). Rare species of yeasts such as C. guilliermondii and Saccharomyces cerevisiae were also identified by molecular methods. Results obtained from antifungal susceptibility testing showed significant differences in MIC values of isoconazole, fenticonazole, and sertaconazole among different species. Overall, a fluconazole-resistant rate of 3% was found among Candida species. Moreover, there was a statistically significant difference in MICs of fenticonazole and clotrimazole between the two most prevalent causative species, C. parapsilosis complex and C. albicans. Correct identification of the causative agents of onychomycosis and performing susceptibility testing could be helpful in choosing the most appropriate antifungal therapy.

Synthesis of composite materials combining magnetic metal-organic frameworks and conjugated organic frameworks for selective extraction of carbendazim and thiabendazole residues from Chinese herbal medicine samples

A magnetic metal-organic framework MIL-68(Al) and a covalent organic framework were used as magnetic solid-phase extraction (MSPE) adsorbents in combination with high-performance liquid chromatography ultraviolet detection (HPLC-UV) to detect carbendazim (CBZ) and thiabendazole (TBZ). The main parameters affecting the extraction in the MSPE process were studied and optimized. Fe3O4@MIL-68(Al) coated with 1,3,5-tris(4-aminophenyl)benzene and terephthaldehyde (Fe3O4@MIL-68(Al)@TAPB-PDA-COF) was analyzed and verified. The material was proven to be suitable for adsorbing CBZ and TBZ. Various adsorption models were used to study its adsorption mechanism. The adsorption results were in good agreement with the pseudo-second-order kinetic model and Langmuir isotherm model. The maximum adsorption capacities of Fe3O4@MIL-68(Al)@TAPB-PDA-COF over CBZ and TBZ were 54.24 and 67.87 mg g−1, respectively, and the equilibrium adsorption time was 200 min. Fe3O4@MIL-68(Al)@TAPB-PDA-COF with excellent recyclability showed higher adsorption capacity and selectivity. A method based on Fe3O4@MIL-68(Al)@TAPB-PDA-COF combined with HPLC-UV was established under the optimal extraction conditions and used to separate and detect trace imidazole drugs in Chinese herbal samples, achieving a low limit of detection (0.65–1.30 μg L−1) with excellent linear correlation (r > 0.999). The recovery rate and relative standard deviation were 86.05–99.78 % and 0.15–4.90 %, respectively. Therefore, the Fe3O4@MIL-68@TAPB-PDA-COF can be regarded as an effective adsorbent for the pretreatment of CBZ and TBZ drugs in Chinese herbal samples.

Synthesis, Characterization and Biological Evaluation Of 1h-Substituted 2,4,5-Triphenyl Imidazole Derivative.

On the basis of various literature survey, imidazole derivatives show various activity such as antimicrobial, anti-inflammatory, analgesic, antitubercular, anticancer etc. The possible improvements in the activity can be further achieved by slight modifications in the substituents on the basic imidazole nucleus. Thus imidazole offers better pharmacodynamic characteristics. Furthermore, some imidazole drugs, at high concentrations, could exert direct inhibitory effects on membranes, without interference with sterols and sterol esters. Various recent new drugs developments in imidazole derivatives show better effect and less toxicity. The present study focused on synthesis of various 1h-substituted 2,4,5-triphenyl imidazole derivatives. The synthesized compounds were also screened for their antimicrobial and antioxidant properties.

An Overview of Imidazole, Derivatives Ofimidazole and its Pharmacological Applications

In recent decades, many studies have been carried out on heterocycles, especially imidazole rings. The pharmacological properties such as antibacterial, antifungal, anticancer, antiviral and antidiabetic properties Apart from that, there are few side effects. The search for new biologically active imidazoles remains an area of interest An overview of medicinal chemistry. This white paper aims to collect and explain a wealth of information. Antibacterial profile of imidazole. Therefore, it can be used for future development to obtain new effective drug molecules. These heterocycles are important building blocks of functional molecules used in various fields. Used on a daily basis. Emphasis was placed on the bonds that form during the formation of imidazole. The usefulness of these methods is based on functional group compatibility. Processes around the ring and the resulting permutation patterns are described, including domain descriptions. Limitations, Reaction Mechanisms, and Future Challenges. The imidazole ring is part of several important natural products Products containing purines, histamine, histidine, nucleic acids. as polar and ionic Aromatic compounds that improve the pharmacokinetic properties of lead molecules Used as a remedy to optimize poorly proposed solubility and bioavailability parameters soluble lead molecule. Imidazole derivatives occupy a unique position in the art medicinal chemistry. Imidazole drugs have expanded the scope of eliminating various dispositions in clinics dose.

An in vitro study of zinc effect on Trichomonas vaginalis isolated from infected women

The most common non-viral sexual transmission disease in humans, trichomoniasis, is caused by the protozoan parasite Trichomonas vaginalis (STD). Metronidazole is the most frequently recommended of the imidazole drugs used to treat trichomoniasis. In any case, these substances may result in undesired side effects and parasite resistance. As a result, this infection needs to be treated in a different way. Aim: This study was designed to determine the relation between zinc intake and the Trichomonas vaginalis occurrence and also to find out the in vitro effect of zinc on T. vaginalis viability. Methods: This study was carried out on 63 pregnant women whom attended (Azadi Teaching, Kirkuk General and Al-Nasr maternity) Hospitals from December 2021 till April 2022. Specimens of vaginal swabs and serum samples were obtained from all pregnant women. The swabs were first examined directly by normal saline on slide microscopically then inoculated onto Modified Diamond medium. Zinc levels and concentrations in the blood were assessed using serum. Result: T. vaginails was isolated from pregnant women. The overall prevalence among 63 examined samples were positive by direct microscopically and culture with a rate of 5(8%) while 58 (92%) were negative. The 1.5mg/ml zinc concentration was the most effective on T. vaginalis trophozoites number than other concentration of zinc. Conclusion: Zinc is a very important anti- T. vaginalis and can be used it as dilution washing for treatment process.

Synthesis and evaluation of omeprazole-based derivatives as eco-friendly corrosion inhibitors for Q235 steel in hydrochloric acid

The application of expired drugs as corrosion inhibitors is a low-cost, cost-effective and environment-friendly alternative to the expensive degradation process. Against this background, the corrosion inhibition performance and mechanism of imidazole drugs omeprazole (OMP) and its by-products omeprazole sulfide (OMP-1) and omeprazole sulfonate (OMP-2) on Q235 steel in 1 M HCl is investigated by weight loss experiment, electrochemical technology, surface analysis methods (SEM and XPS), quantum chemical calculation and molecular dynamics simulation. The results demonstrate that OMP, OMP-1 and OMP-2 are effective corrosion inhibitors for Q235 steel in 1 M HCl. The inhibition efficiency above 95% is achievable at 298 K with 0.2 mM inhibitor concentration. The test results and fitting data show that they are mixed-type corrosion inhibitors, which comply with Langmuir adsorption isotherm. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) further confirmed these three inhibitor molecules playing the role of corrosion inhibition by adsorbing on the surface of Q235 steel to form a film barrier. The corrosion inhibition mechanism of omeprazole on metal surface is also discussed.

An Insight into the Biological Properties of Imidazole‐Based Schiff Bases: A Review

AbstractImidazole is an azole heterocycle containing two non‐adjacent nitrogen atoms added greatly to natural products and synthetic compounds. The planar ring system associated with electron‐rich nitrogen donors are essential for the greater affinity of imidazole derivatives to bind with various bio receptors and enzymes via weak interactions. It improves the pharmacokinetic properties of the pilot molecules consequently utilized as a solution for aqueous solubility, bioavailability, and toxicity parameters since it is a polar compound. An organic molecule with imidazole derivatives has acquired a sustainable place in medical and clinical fields. The consolidation of the imidazole unit is a significant synthetic technique in drug development. The imidazole‐based Schiff bases with enormous therapeutic properties has encouraged the scientists to focus on recently initiated novel chemotherapeutic agents such as anticancer, antimicrobial, antioxidant, antiviral, antileishmanial, etc. Imidazole drugs have expanded the degree of curing different dispositions in clinical medications. Herein, we have reported the structural feature of imidazole, design, synthesis of imidazole derivatives, and its significance. This review aims to describe the reported materials of imidazole‐based Schiff bases and their derivatives which offer fruitful scope in the field of medicinal chemistry.

Preparation and properties of chitosan-based bacteriostatic agents and their application in strawberry bacteriostatic preservation.

The purpose of this study is to develop a green and safe chitosan-based preservative which can be applied in strawberry preservation. Chitosan (CS) was treated by 2,2,6,6-tetramethylpiperidine oxygen radical/laccase oxidation system (TEMPO/laccase oxidation system), which was mainly used to prepare TEMPO/laccase chitosan (TLCS). Furthermore, on this basis, the structure and performance of TLCS were also studied. The results showed that compared with CS, the solubility of TLCS improved, and the kinetic viscosity reduced significantly. Next, a cinnamaldehyde-TEMPO/laccase chitosan (CIN-TLCS) antibacterial agent was prepared by covalently combining the aldehyde group in cinnamaldehyde (CIN) and the amino group in CS. It was found that CIN combined with TLCS through covalent bonds, which changed the structure and crystallinity of TLCS. In addition, the total antioxidant capacity of CIN-TLCS also improved, which was necessary for the application of CIN-TLCS in extending shelf life. Cytotoxicity experiments showed that CIN-TLCS had no cytotoxicity. Furthermore, strawberries were used to explore the actual bacteriostatic and fresh-keeping effects of CIN-TLCS. The experiment found that CIN-TLCS could maintain the freshness of strawberries at room temperature (23 ± 1°C) for 5 days and had positive effects on strawberry color, loss-weight rate, hardness and pH. These results showed that CIN-TLCS could be used as a potential preserving agent for fruit storage. PRACTICAL APPLICATION: To obtain a green, safe and effective food preservative, chitosan (CS) was modified by a 2,2,6,6-tetramethylpiperidine oxygen radical/laccase oxidation system (TEMPO/laccase oxidation system) to get TEMPO/laccase chitosan (TLCS) and cinnamic aldehyde-TEMPO/laccase chitosan (CIN-TLCS). At the same time, the structure and antibacterial properties of TLCS and CIN-TLCS were analyzed, and their possibility as a new green and safe strawberry preservative was studied. Compared with oxazolidine, imidazole and triazole commercial drugs, CIN-TLCS has the advantages of low price, no pollution, no cytotoxicity and no drug resistance.

Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: a prospective, multicentre, open-label, cohort study

SummaryBackgroundStaging and treatment of human African trypanosomiasis caused by Trypanosoma brucei gambiense (g-HAT) required lumbar puncture to assess cerebrospinal fluid (CSF) and intravenous drugs that cross the blood–brain barrier for late-stage infection. These procedures are inconvenient in rural health systems of disease-endemic countries. A pivotal study established fexinidazole as the first oral monotherapy to be effective against non-severe stage 2 g-HAT. We aimed to assess the safety and efficacy of fexinidazole in early g-HAT.MethodsIn this prospective, multicentre, open-label, single-arm cohort study, patients with stage 1 or early stage 2 g-HAT were recruited from eight treatment centres in the Democratic Republic of the Congo. Primary inclusion criteria included being older than 15 years, being able to ingest at least one complete meal per day (or at least one sachet of Plumpy'Nut®), a Karnofsky score higher than 50, evidence of trypanosomes in the blood or lymph but no evidence of trypanosomes in the CSF, willingness to be admitted to hospital to receive treatment, having a permanent address, and being able to comply with the follow-up visit schedule. Exclusion criteria included severe malnutrition, inability to take medication orally, pregnant or breastfeeding women, any clinically important medical condition that could jeopardise patient safety or participation in the study, severely deteriorated general status, any contraindication to imidazole drugs, HAT treatment in the past 2 years, previous enrolment in the study or previous intake of fexinidazole, abnormalities on electrocardiogram that did not return to normal in pretreatment repeated assessments or were considered clinically important, QT interval corrected using Fridericia's formula of at least 450 ms, and patients not tested for malaria or not having received appropriate treatment for malaria or for soil-transmitted helminthiasis. Patients were classified into stage 1 or early stage 2 g-HAT groups following evidence of trypanosomes in the blood, lymph, and absence in CSF, and using white-blood-cell count in CSF. Patients received 1800 mg fexinidazole once per day on days 1–4 then 1200 mg fexinidazole on days 5–10. Patients were observed for approximately 19 months in total. Study participants were followed up on day 5 and day 8 during treatment, at end of treatment on day 11, at end of hospitalisation on days 11–18, at week 9 for a subset of patients, and after 6 months, 12 months, and 18 months. The primary endpoint was treatment success at 12 months. Safety was assessed through routine monitoring. Analyses were done in the intention-to-treat population. The acceptable success rate was defined as treatment efficacy in more than 80% of patients. This study is completed and registered with ClinicalTrials.gov (NCT02169557).FindingsPatients were enrolled between April 30, 2014, and April 25, 2017. 238 patients were recruited: 195 (82%) patients with stage 1 g-HAT and 43 (18%) with early stage 2 g-HAT. 189 (97%) of 195 patients with stage 1 g-HAT and 41 (95%) of 43 patients with early stage 2 g-HAT were finally included and completed the 10 day treatment period. Three patients with stage 1 g-HAT died after the 10 day treatment period and before the 12 month primary follow-up visit, considered as treatment failure and were withdrawn from the study. Treatment was effective at 12 months for 227 (99%) of 230 patients (95% CI 96·2–99·7): 186 (98%) of 189 patients (95·4–99·7) with stage 1 and 41 (100%) of 41 patients (91·4–100·0) with early stage 2, indicating that the primary study endpoint was met. No new safety issues were observed. The most frequent adverse events were headache and vomiting. In total, 214 (93%) of 230 patients had treatment-emergent adverse events, mainly common-terminology criteria for adverse events grades 1 to 3. None led to treatment discontinuation.InterpretationFexinidazole is a valuable first-line treatment option in the early stages of g-HAT.FundingThrough the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation, the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (also known as DGIS; Netherlands), the Norwegian Agency for Development Cooperation (also known as Norad; Norway), the Federal Ministry of Education and Research (also known as BMBF) through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the HAT campaign.TranslationFor the French translation of the abstract see Supplementary Materials section.

3D printed clotrimazole intravaginal ring for the treatment of recurrent vaginal candidiasis

Vulvovaginal candidiasis is a vaginal infection caused by the fungal pathogen Candida albicans that, most commonly, affects women of reproductive age. Its first-line treatment consists in topical applications of conventional drug formulations (e.g., creams, gels, tablets) containing imidazole drugs. The treatment involves single or multiple daily applications and, in the case of recurrences, daily administration of oral antifungal drugs for up to one month.Intravaginal rings are flexible, biocompatible medical devices that, compared to conventional drug formulations, offer the possibility of a controlled vaginal drug delivery over a determined period with a single application, thus increasing patient compliance. Among innovative manufacturing techniques, in recent years, fused deposition modeling 3D printing has emerged in the pharmaceutical field to produce different therapeutics combining drugs and polymers. This technique allows to print objects layer by layer with many different thermoplastic materials after a computer-assisted design.Thermoplastic polyurethanes are flexible and biocompatible materials that can be efficiently employed for the manufacturing of drug release systems, already utilized to prepare vaginal devices.In this work, we produced a clotrimazole-loaded intravaginal ring by fused deposition modeling 3D printing combining the drug with thermoplastic polyurethane using hot melt extrusion. The rings were computer-designed and then printed with two different drug concentrations (i.e., 2% and 10% w/w).The intravaginal rings were first tested in an agar-diffusion test to evaluate their effectiveness against C. albicans; and the 10% loaded ring was selected for further studies. Drug release was evaluated in two different media (i.e., 50% ethanol and vaginal fluid simulant) showing a sustained release over a period of seven days. Next, in vitro time-kill analysis against C. albicans in simulated vaginal fluid was performed and displayed a complete growth inhibition after 5 days, compared to the control.These results suggest a potential application of these 3D printed intravaginal rings for the treatment of vulvovaginal candidiasis and for the long-time treatment of recurrences.

Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis.

BackgroundMicrosporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans.ObjectivesIn clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail.MethodsIn this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto.ResultsAt half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ.ConclusionsThe results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids.

The antibacterial activity of imidazole and imidazolium salts is highly dependent upon their lipophilicity, which can be tuned through the introduction of different hydrophobic substituents on the nitrogen atoms of the imidazole or imidazolium ring of the molecule. Taking this into consideration, we have synthesized and characterized a series of imidazole and imidazolium salts derived from L-valine and L-phenylalanine containing different hydrophobic groups and tested their antibacterial activity against two model bacterial strains, Gram-negative E. coli and Gram-positive B. subtilis. Importantly, the results demonstrate that the minimum bactericidal concentration (MBC) of these derivatives can be tuned to fall close to the cytotoxicity values in eukaryotic cell lines. The MBC value of one of these compounds toward B. subtilis was found to be lower than the IC50 cytotoxicity value for the control cell line, HEK-293. Furthermore, the aggregation behavior of these compounds has been studied in pure water, in cell culture media, and in mixtures thereof, in order to determine if the compounds formed self-assembled aggregates at their bioactive concentrations with the aim of determining whether the monomeric species were in fact responsible for the observed antibacterial activity. Overall, these results indicate that imidazole and imidazolium compounds derived from L-valine and L-phenylalanine—with different alkyl lengths in the amide substitution—can serve as potent antibacterial agents with low cytotoxicity to human cell lines.

Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation.

Refractory otomycosis is a common condition that is difficult to treat. This study aimed to evaluate the effectiveness of 1% topical voriconazole drops in the treatment of otomycosis. This retrospective analysis was conducted from November 2017 to November 2019. Patients who had refractory otomycosis without tympanic membrane perforation confirmed by microbial culture and fluorescent staining were included in the study. All patients were treated with 1% topical voriconazole drops hourly at daytime for 2 weeks. Evaluation of effectiveness was conducted 1 month after the completion of topical voriconazole treatment. Before and after topical voriconazole treatment, hearing tests were performed in all patients. Fifty-five patients were included in this study. The reasons for refractoriness were resistant recurrence to imidazole drugs (50 cases, 90.9%) and difficulty in cleaning the external auditory canal (5 cases, 9.1%). The most common strain was Aspergillus terreus (50.9%), followed by Aspergillus flavus (29.1%), Aspergillus niger (10.9%), and Aspergillus fumigatus (9.1%). After 2 weeks of treatment with 1% topical voriconazole drops, otomycosis in all patients was resolved. There was no significant change in bone conduction before and after topical voriconazole treatment (paired t-test, P = 0.5023; linear correlation analysis, R2 = 0.98; equation, y = 1.003x-0.284). Adverse effects, such as blurred vision and phototoxicity, were not observed in any patient. Administration of 1% topical voriconazole drops was effective and safe in the treatment of refractory otomycosis without tympanic membrane perforation within 2 weeks.

Supercritical fluid extraction of imidazole drugs from cosmetic and pharmaceutical products

An effective method for isolating common imidazole drugs clotrimazole (CT) and ketoconazole (KCZ) from cosmetic and pharmaceutical products based on supercritical fluid extraction (SFE) was developed. Creams, tablets and cosmetic shampoos underwent supercritical carbon dioxide fluid extraction and CT and KCZ were determined by reverse-phase high performance liquid chromatography. All supercritical fluid extractions were performed with a 10-min static step, followed by a 15 min dynamic step using acetonitrile as the modifier. After extraction by SFE, KCZ and CT were separated on a C18 column using an isocratic mobile phase that consisted of methanol/water/diethylamine/glacial acetic acid (80:20:0.3:0.2, v/v, pH 7.0) at a flow rate of 1.0 mL/min. The eluates from column were monitored by absorbance at 224 nm using a diode array detector. This developed approach was validated by assaying commercial pharmaceuticals for the routine quantification of CT and KCZ in various formulations. The calibration curves for CT and KCZ were linear over the ranges of 50-250 μg/mL and 25-250 μg/mL, respectively. The detection limits of CT and KCZ were 2.31 μg/mL and 0.42 μg/mL, respectively, and the limits of quantitation were 7.70 μg/mL and 1.40 μg/mL, respectively. These drugs contents were found to be in good agreement with the label claim values. Satisfactory extraction recoveries ranging from 90.8% to 97.2% were obtained from five replicate extractions.

Preparation of Nanofungicides Based on Imidazole Drugs and Their Antifungal Evaluation.

In spite of modern crop protection measures, the overall crop losses due to pests and pathogens are huge. Rhizoctonia solani, Macrophomina phaseolina, Sclerotium rolfsii, and Fusarium oxysporum are one of the most devastating soil-borne fungi and cause numerous plant diseases. Therefore, the present study aimed to systematically design and develop new nanofungicides based on imidazole drugs, clotrimazole, econazole nitrate, and miconazole nitrate, for effective and efficient management of plant diseases. The assessment of these antifungal medicines for their fungicide likeness using Hao's rule and their enzyme inhibitory potential by molecular docking was helpful in ensuring their utility as antifungal agents in managing phytopathogenic fungi. Nanotechnological strategies were used to develop nanoformulations of test compounds in poly(ethylene glycol) 300 for further augmenting their bioactivity. Transmission electron microscopy studies confirmed the nanosize of the prepared products. Analysis of their in vitro and in vivo antifungal properties revealed their usefulness in controlling the test fungi, R. solani, M. phaseolina, S. rolfsii, and F. oxysporum. Excellent in vitro antifungal activities were displayed by the clotrimazole nanoformulation with a median effective dose (ED50) of 1.18 μg/mL against R. solani, the econazole nitrate nanoformulation with an ED50 of 5.25 μg/mL against S. rolfsii, and the miconazole nitrate nanoformulation with an ED50 of 1.49 and 1.82 μg/mL against M. phaseolina and F. oxysporum. Furthermore, in vivo studies against test fungi demonstrated the antifungal potency of all the nanoformulations with disease incidences ranging from 11.11 to 27.38% in plants treated with nanoformulations of test chemicals as compared to the inoculated control (39.68-72.38%).

Chemistry and Pharmacology of Luliconazole (Imidazole Derivative): A Novel Bioactive Compound to Treat Fungal Infection-A Mini Review

Background: Currently, ringworm treatment drugs include two major categories: first, propylene amine drugs, such as terbinafine, butenafine and naftifine, which exert their bactericidal effects through inhibiting squalene cyclase, causing the lack of ergosterol and accumulation of squalene. The second category of imidazole drugs includes miconazole, econazole, clotrimazole, ketoconazole and bifonazole. Mechanism: These synthetic antifungal agents exhibits their action by inhibiting the lanosterol 14α- demethylation activity of fungal cell, leading to the prevention of the ergosterol synthesis of cell membrane, changing the cell membrane permeability, and resulting in the loss of important intracellular fungal material and causing fungal death. Applications: At present, Imidazole antifungal agents are commonly used drugs in clinical treatment of ringworm with extensive clinical applications. Conclusion: The present review covers the chemistry and detailed pharmacology aspects of luliconazole.

Novel insights into P450 BM3 interactions with FDA-approved antifungal azole drugs

Flavocytochrome P450 BM3 is a natural fusion protein constructed of cytochrome P450 and NADPH-cytochrome P450 reductase domains. P450 BM3 binds and oxidizes several mid- to long-chain fatty acids, typically hydroxylating these lipids at the ω-1, ω-2 and ω-3 positions. However, protein engineering has led to variants of this enzyme that are able to bind and oxidize diverse compounds, including steroids, terpenes and various human drugs. The wild-type P450 BM3 enzyme binds inefficiently to many azole antifungal drugs. However, we show that the BM3 A82F/F87V double mutant (DM) variant binds substantially tighter to numerous azole drugs than does the wild-type BM3, and that their binding occurs with more extensive heme spectral shifts indicative of complete binding of several azoles to the BM3 DM heme iron. We report here the first crystal structures of P450 BM3 bound to azole antifungal drugs – with the BM3 DM heme domain bound to the imidazole drugs clotrimazole and tioconazole, and to the triazole drugs fluconazole and voriconazole. This is the first report of any protein structure bound to the azole drug tioconazole, as well as the first example of voriconazole heme iron ligation through a pyrimidine nitrogen from its 5-fluoropyrimidine ring.

Enantioseparation of Selected Imidazole Drugs Using Dual Cyclodextrin-Modified Micellar Electrokinetic Chromatography.

Particular attention has been paid to capillary electrophoresis as versatile and environmentally friendly approach for enantioseparations of a wide spectrum of compounds. Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) is a method of choice to provide effective separation toward hydrophobic and uncharged stereoisomers. The chiral discrimination of the solutes relies upon the partitioning between a given CD in the aqueous phase and micelles formed from a surfactant. Synergistic combinations of chiral selectors, surfactant, and modifier contribute to successful enantioseparations of the enantiomers. In this chapter, an application of CD-MEKC for the enantioseparation of selected imidazole drugs employing a dual CDs system is described.