Miconazole Research Articles

Проблемы диагностики и лечения бактериального вагиноза в активном репродуктивном возрасте

Aim: to assess the efficacy and safety of vaginal capsules containing metronidazole 100 mg and myconazole nitrate 100 mg in women with bacterial vaginosis (including recurrent vaginosis). Patients and Methods: 62 women were enrolled. Group 1 included 32 women with firstly diagnosed bacterial vaginosis. Group 2 included 30 women with recurrent bacterial vaginosis. Vaginal capsules containing 100 mg of metronidazole and 100 mg of miconazole nitrate (Gynocaps) or Gynocaps plus peroral metronidazole 250 mg twice daily (combined therapy) were prescribed. Group 1 and group 2 were divided into subgroups, i.e., 1A (n=20) and 1B (n=12), 2A (n=18) and 2B (n=12), based on treatment (monotherapy or combined therapy, respectively). Treatment efficacy was assessed 1 month and 12 months after completing treatment. Results: the major symptom in both groups was off-white vaginal discharge. Diffuse vulvar redness was more common in group 1 while petechiae were more common in group 2 (p<0.05). Lactobacillus spp. counts were reduced in all women, mixed infections were predominant. In group 2, significantly higher counts of anaerobic and yeast flora compared to group 1 were reported (p<0.05). In group 1, no significant differences in the improvement of clinical signs after both treatment regimens were reported. Meanwhile, in group 2, clinical signs improved more rapidly after combined treatment. However, combined treatment was associated with adverse effects. A reduction in the total bacterial mass and logarithmic growth of anaerobic microflora was observed irrespective of the treatment regimen. No recurrences of bacterial vaginosis were reported. Conclusions: a 10-day treatment course of combined vaginal capsules containing metronidazole 100 mg and miconazole nitrate 100 mg improves clinical signs, eliminates complaints, and improves vaginal microflora owing to Lactobacillus growth without adverse reactions. In recurrent vaginosis, this agent should be used in combination with antibiotics. KEYWORDS: bacterial vaginosis, active reproductive age, metronidazole, miconazole nitrate, Lactobacillus. FOR CITATION: Chebotareva Yu.Yu. Diagnosis and treatment of bacterial vaginosis during active reproductive age. Russian Journal of Woman and Child Health. 2021;4(3):218–224 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-218-224.

Effect of Lactic Acid Content into on during Miconazole Eye Drops to be Used for Infection Preventive

Purpose: The aims of this study were to prepare a 0.1% Miconazole (MCZ) eye-drop solution and to evaluate the stability and physical properties of the preparation.

Санация влагалища как способ профилактики послеоперационных осложнений у пациенток с различной гинекологической патологией

Aim: to assess the efficacy of vaginal care hygiene in women with various gynecological disorders requiring surgical interventions to reduce postoperative complications. Patients and Methods: eighty women aged 39–60 with various gynecological diseases diagnosed with vaginal microbiota abnormalities (E.F. Kir vaginal smear cleanliness grade 3–4) during the preoperative evaluation before a scheduled surgery underwent a complex clinical laboratory examination and treatment. The study group included 60 women who received a complex vaginal preparation containing 100 mg metronidazole and 100 mg miconazole nitrate (1 capsule at night) plus oral metronidazole (500 mg daily) five days before and after surgery. In the control group, vaginal hygiene was performed according to the general management standards (vaginal chlorhexidine 16 mg twice daily or oral metronidazole 500 mg daily for five days) in the presence of complaints and/or abnormalities in vaginal smears identified by microscopy. Results: 14 days after surgery, normal vaginal microbiota was reported in all study group women (vaginal smear cleanliness grade 1–2), while in the control group, vaginal smear cleanliness grade III-IV was reported in 8 women. Postoperative complications occurred in the control group only, i.e., two women were diagnosed with postoperative wound dehiscence after procedures for genital prolapse and two women were diagnosed with subacute infectious inflammatory pelvic disorders. Conclusion: our findings show the efficacy of vaginal hygiene with a complex vaginal preparation before and after pelvic floor surgery, as demonstrated by preventing bacterial vaginosis recurrences and reducing the rate of postoperative complications. KEYWORDS: bacterial vaginosis, vulvovaginal candidiasis, vaginal infection, postoperative complications, vaginal hygiene, metronidazole, miconazole. FOR CITATION: Manukhin I.B., Manukhina E.I., Safaryan I.R. Vaginal hygiene to prevent postoperative complications in various gynecological diseases. Russian Journal of Woman and Child Health. 2021;4(4):322–327 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-322-327.

Mycetoma trichophyton

A 2-year-old female child admitted to the hospital due to a palpable mass at her scalp referred by her parents. Her past medical history was clear. The clinical examination revealed edema, redness/erythema, blisters, tenderness and itching. No neurological changes were referred, no hair loss occurred and no other areas of the body were affected. The initial evaluation included X-rays, an ultrasonography and a magnetic resonance imaging (MRI) scan. The imaging findings were not pathognomonic but in combination with the clinical features, the differential diagnosis shrinked between mycetoma and pilomatrixoma (or calcifying epithelioma of Malherbe). For further evaluation, a small specimen of the scalp was obtained by scraping the skin with a scalpel. Cytological investigation revealed fungi infection caused by trichophyton species. So the final accurate diagnosis was mycetoma trichophyton. Patient was treated with miconazole nitrate (daktarin cream 2%), 1x3 for 15 days. First follow up (day 15) showed improvement to complete cure. At the second follow up (day 30) there was no evidence of relapse. Mycetoma trichophyton must be differentiated from pilomatrixoma (which may appear with similar clinical and sonographic features), cutaneous tuberculosis, folliculitis, actinomycosis, chromomycosis, sporotrichosis, coccidioidomycosis, blastomycosis of the skin, botryomycosis etc. Dermatophyte infections usually occur in immuno compromised patients. In our case, the young patient was healthy and no medication administration had previously happened. A trichophyton infection mainly causes superficial lesions to the skin, nails and hair, deeper dermis and subcutaneous tissue anywhere on the body but most frequently at the lower extremities.

Management of recurrent aphthous ulcers exploiting polymer-based Muco-adhesive sponges: in-vitro and in-vivo evaluation

Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.

Solidified Reverse Micellar Solution-Based Lipid Microparticles of Miconazole Nitrate: Formulation Design, Biopharmaceutical Characterization, and Dissolution Studies

The present work was aimed at formulating solidified reverse micellar microparticles (SRMMs) using templated lipids (Softisan 154, stearic acid, and Phospholipon ®90H) for improved biopharmaceutical performance, dissolution of miconazole nitrate. SRMMs containing miconazole nitrate (MN) (1, 2, and 3% w/w) were formulated using Softisan® 154 (SOFT) and stearic acid (ST) and their combinations, containing Phospholipon® 90H (P90H) by melt homogenization employing Polysorbate 80 as the surfactant. The microparticles were freeze-dried, characterized, and optimized batches evaluated for in vitro dissolution in methanolic HCl and antifungal activity. The average SRMM yield was 70%. Entrapment efficiency and loading capacity determination showed that the lipid matrix composed of Softisan® 154 and Phospholipon® 90H (7:3) possessed greater entrapment than the other matrices with the 5% SOFT + P90H matrix containing 3% MN entrapping 98.48% of the drug. Preliminary anticandidal evaluation of the formulations showed significant activity of all the formulations containing drug. DSC analysis of the lipid excipients and matrices showed slight modifications in the physical nature of the excipients. Further analysis using X-ray diffraction showed retention of drug form in the formulations though with slight alterations in d-spacings of the X-ray diffractograms. In vitro dissolution studies of the optimized batches revealed a significant (p < 0.05) increase in dissolution rates of optimized SLM batches compared with pure MN. Kinetic modelling of the in vitro dissolution data revealed that most of the matrix systems evaluated best fitted the Korsenmeyer-Peppas model. SRMMs improved the in vitro dissolution and antifungal activity of MN.

Simultaneous quantification of five pharmaceuticals and personal care products in biosolids and their fate in thermo-alkaline treatment

The presence of pharmaceuticals and personal care products (PPCPs) in biosolids applied to farmland is of concern due to their potential accumulation in the environment and the subsequent effects on humans. Thermo-alkaline hydrolysis (TAH) is a method used for greater stabilization of biosolids after anaerobic digestion. In this work, the effect of TAH on five selected PPCPs including fluoroquinolone antibiotics, ciprofloxacin (CIP), and ofloxacin (OFLX), and three commonly used antimicrobial agents, miconazole (MIC), triclosan (TCS) and triclocarban (TCC) was evaluated. At the onset, extraction and analytical methods were optimized for maximum simultaneous recovery and LC-MS quantification of the target PPCPs from both water and biosolids for improved accuracy. The compounds were detected in the range of 54 ± 3 to 6166 ± 532 ng/g in raw biosoilds collected from a local WWTP. Next, batch control adsorption experiments of the selected PPCPs were conducted in various sludges, which indicated about 89%–98% sorption of the PPCPs onto solid phase due to their high octanol-water coefficients. Subsequently, thermo-alkaline (pH 9.5, 75 °C, 45 min) hydrolysis (TAH) was conducted to determine the extent of degradation of these compounds in deionized (DI) water and biosolids due to treatment. The degradation of these compounds due to TAH ranged from 42% to 99% and 37%–41% in pure water and biosolids, respectively, potentially lowering their risk in the environment due to land application. A list of compounds for which the optimized analytical method potentially can be used for detection and quantification in environmental samples is provided in the supporting document.

Repositioning miconazole nitrate for malaria: Formulation of sustained release nanostructured lipid carriers, structure characterization and in vivo antimalarial evaluation

It has been previously claimed that miconazole (MNZ) has activity against Plasmodium falciparum in vitro. Therefore, this study aims to evaluate the potential of MNZ as an alternative antimalarial agent. MNZ was entrapped in nanostructured lipid carriers (NLC) based on Softisan®154 and soybean oil admixtures. Batches of MNZ-loaded NLC were characterized for particle size and surface charge, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), and encapsulation efficiency (EE%). In vitro release and in vivo antimalarial evaluations (using a murine model) were also carried out. Particle size of NLC ranged from 175 to 525 nm, and surface charge from −20 to −27 mV. DSC thermograms showed amorphization of MNZ at low melting points and enthalpies. X-ray diffractograms showed broader and weaker patterns with few characteristic peaks of MNZ, and high EE% of 90–98% were recorded. In vitro release study showed controlled release effect with about 82% of MNZ released after 8 h. In vivo clearance of parasitaemia was drug loading-dependent and compared favourably with the positive control. Stability testing of the MNZ-loaded NLC exhibited no significant (p > 0.05) changes in EE% compared to initial analysis. Thus, MNZ could be repurposed as an effective alternative for the treatment of malaria.

Nanoparticulated Systems Based on Natural Polymers Loaded with Miconazole Nitrate and Lidocaine for the Treatment of Topical Candidiasis.

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24h.

Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.

The occurrence and recurrence of mucosal biofilm-related Candida infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused by Candida spp., for example, affect 70 to 75% of women at least once during their lives. Miconazole (MCZ) is the preferred topical treatment against these fungal infections, yet it has only moderate antibiofilm activity. Through screening of a drug-repurposing library, we identified the quaternary ammonium compound domiphen bromide (DB) as an MCZ potentiator against Candida biofilms. DB displayed synergistic anti-Candida albicans biofilm activity with MCZ, reducing the number of viable biofilm cells 1,000-fold. In addition, the MCZ-DB combination also resulted in significant killing of biofilm cells of azole-resistant C. albicans, C. glabrata, and C. auris isolates. In vivo, the MCZ-DB combination had significantly improved activity in a vulvovaginal candidiasis rat model compared to that of single-compound treatments. Data from an artificial evolution experiment indicated that the development of resistance against the combination did not occur, highlighting the potential of MCZ-DB combination therapy to treat Candida biofilm-related infections.

Caracterización de cristales líquidos con Miconazol en sistemas bifásicos por microscopía de polarización

Introducción: las emulsiones son un tipo de preparado farmacéutico muy utilizado en aplicación tópica consistentes en sistemas bifásicos de aceite-agua o agua-aceite, donde el principio activo deseado se incorpora en una de las fases dependiendo de su solubilidad. Diversos estudios demuestran que la estabilidad es mayor en emulsiones con estructuras líquido-cristalinas. El principio activo liposoluble Miconazol, que actúa como antimicótico, se solubiliza en la fase oleosa de la emulsión y en la fracción de la cadena hidrocarbonada de los cristales líquidos. Método: se utilizaron técnicas microscópicas para analizar las características de una emulsión convencional y de otra con cristales líquidos, a las que se les incorporó el principio activo Miconazol. Se determinaron las dimensiones de las gotas de la fase interna y mediante microscopía de polarización se caracterizaron los cristales líquidos. Resultados: el análisis de las imágenes microscópicas permitió determinar que en las formulaciones con cristales líquidos con y sin Miconazol, aproximadamente el 80 % de las gotas tienen dimensiones en el intervalo 0,5 µm - 1 µm. Las observaciones microscópicas con luz polarizada nos permitieron determinar que los cristales líquidos tienen birrefringencia con la formación de cruces de extinción uniáxicas negativas, las cuales son características de las fases liotrópicas laminares con texturas cónicas focales. Conclusiones: los resultados muestran que el agregado de Miconazol, no interfiere con la formación de la estructura de los cristales líquidos, por lo que estas dependen de los componentes de la formulación y de la técnica de preparación.

Development of a Surface Coating Technique with Predictive Value for Bead Coating in the Manufacturing of Amorphous Solid Dispersions.

The aim of this paper was to investigate whether a surface coating technique could be developed that can predict the phase behavior of amorphous solid dispersions (ASDs) coated on beads. ASDs of miconazole (MIC) and poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) in methanol (MeOH) were studied as a model system. First, the low crystallization tendency of the model drug in MeOH was evaluated and confirmed. In a next step, a drug loading screening was performed on casted films and coated beads in order to define the highest possible MIC loading that still results in a one-phase amorphous system. These results indicate that film casting is not suitable for phase behavior predictions of ASDs coated on beads. Therefore, a setup for coating a solid surface was established inside the drying chamber of a spray dryer and it was found that this surface coating technique could predict the phase behavior of MIC-PVP-VA systems coated on beads, in case an intermittent spraying procedure is applied. Finally, spray drying was also evaluated for its ability to manufacture high drug-loaded ASDs. The highest possible drug loadings that still result in a one-phase amorphous system were obtained for bead coating and its predictive intermittent surface coating technique, followed by spray drying and finally by film casting and the continuous surface coating technique, thereby underlining the importance for further research into the underexplored bead coating process.

Prophylactic efficacy of enteral antifungal administration of miconazole for intestinal perforation, especially for necrotizing enterocolitis: a historical cohort study at a single institution.

Despite improvements in neonatal intensive care, the outcomes of extremely-low-birth-weight infants (ELBWIs) with surgical diseases remain to be improved. We started administering enteral miconazole (MCZ) to ELBWIs from 2002 to prevent fungal infection. Since then, the incidence of intestinal perforation has significantly decreased. We investigated this prophylactic effect of MCZ against necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) and explored a new prophylactic concept against intestinal perforation. We designed a historical cohort study to evaluate the effect of MCZ for intestinal perforation in ELBWIs who underwent treatment in our neonatal intensive-care unit between January 1998 and December 2005. We divided these cases into two groups: the Pre-MCZ group and the Post-MCZ group. We compared the morbidity, clinical outcomes and pathological features of NEC and FIP. The rate of intestinal perforation with NEC was significantly reduced after the introduction of MCZ (p = 0.007, odds ratio; 3.782, 95% confidence interval; 1.368-12.08). The pathological findings of NEC specimens showed that the accumulation of inflammatory cells was significantly reduced in the Post-MCZ group when compared with the Pre-MCZ group (p < 0.05). The efficacy of the enteral administration of MCZ on intestinal perforation with NEC highlights a new prophylactic concept in the clinical management of ELBWIs.

The corrosion promoting mechanism of Aspergillus niger on 5083 aluminum alloy and inhibition performance of miconazole nitrate

The corrosion behavior of 5083 aluminum alloy in the medium with Aspergillus niger and the inhibitory effect of miconazole nitrate (MN) were studied. High-performance liquid chromatography analysis confirmed that oxalic acid was the major ingredient of the metabolites of Aspergillus niger, which was responsible for the severe corrosion of aluminum alloy. According to weight loss test, the inhibition efficiency of MN against the corrosion of aluminum alloy caused by A. niger in culture medium reached 90% at 20 mg/L. The results herein demonstrate that MN possesses a considerable potential for preventing the microbiologically influenced corrosion caused by fungus.

Antifungal drug miconazole ameliorated memory deficits in a mouse model of LPS-induced memory loss through targeting iNOS

Alzheimer’s disease (AD) is closely related to neuroinflammation, and the increase in inflammatory cytokine generation and inducible nitric oxide synthase (iNOS) expression in the brain of a patient with AD is well known. Excessive cytokines can stimulate iNOS in microglia and astroglia and overproduce nitric oxide, which can be toxic to neurons. The disease–gene–drug network analysis based on the GWAS/OMIM/DEG records showed that miconazole (MCZ) affected AD through interactions with NOS. Inhibiting iNOS can reduce neuroinflammation, thus preventing AD progression. To investigate the prophylactic role of antifungal agent in the AD development, a lipopolysaccharide-induced memory disorder mouse model was used, and cognitive function was assessed by Morris water maze test and passive avoidance test. MCZ treatment significantly attenuated cognitive impairment, suppressed iNOS and cyclooxygenase-2 expression, and activation of astrocyte and microglial BV2 cells, as well as reduced cytokine levels in the brains and lipopolysaccharide-treated astrocytes and microglia BV2 cells. In further mechanism studies, Pull-down assay and iNOS luciferase activity data showed that MCZ binds to iNOS and inhibited transcriptional activity. Our results suggest that MCZ is useful for ameliorating the neuroinflammation-mediated AD progression by blocking iNOS expression.

A New Analytical HPLC Method for Quantification of Mometasone Furoate, Nadifloxacin and Miconazole Nitrate in Semisolid Dosage Form

A New Analytical HPLC Method for Quantification of Mometasone Furoate, Nadifloxacin and Miconazole Nitrate in Semisolid Dosage Form

Antifungal susceptibility of oral isolates of Candida species from chronic kidney disease patients on chronic dialysis

Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36°C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.

Development and characterization of miconazole nitrate transfersomal gel

Miconazole nitrate (MIC) is an antifungal drug used for the treatment of superficial fungal infections. However, it has low skin permeability. Hence, the basic idea behind the development of such a system, transfersomes is to maintain a sustain release of drug from the dosage form and for target delivery. Miconazole nitrate was formulated as transfersomes, half-life can be increased and the desired effect can be obtained. MIC transfersomes were prepared using a thin lipid film hydration technique. The prepared transfersomes were evaluated with respect to entrapment efficiency (EE%), particle size, and quantity of in vitro drug released to obtain an optimized formulation. The optimized formulation of MIC transfersomes was incorporated into a Carbapol 934 gel base which was for drug content, pH, spreadability, viscosity, in vitro permeation, and in vitro activity. The prepared MIC transfersomes had a high EE% ranging from 65.45% to 80.11%, with small particle sizes ranging from 368 nm to 931 nm. The in vitro release study suggested that there was an inverse relationship between EE% and in vitro release. In 24 hrs the drug release was observed ranging from 79.08% to 88.72%. The kinetic analysis of all release profiles was found to follow Higuchi’s diffusion model. All independent variables had a significant effect on the dependent variables (p-values &lt; 0.05). Therefore, Miconazole nitrate in the form of transfersomes has the ability to penetrate the skin, overcoming the stratum corneum barrier. When the data subjected to zero order and first order kinetics model, a linear relationship was observed with high R2 values for zero order model as compared to first order model and suggested that the formulations followed zero order sustained release.

Quantum chemical and experimental exploration of biological activity and inhibitory potential of new acylated oligosaccharides from Pistacia integerrima J. L. Stewart ex Brandis

The new biologically active integrisides A (1) and B (2) have been isolated from the methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis. The antibacterial activity of both the integrisides were tested against four pathogenic bacterial strains, two Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and two Gram-negative (Escherichia coli, Pseudomonas aeruginosa) as well as four fungal strains (Microsporum canis, Aspergillus clavatus, Candida albicans and Candida glabrata). Both the isolated compounds showed significant results analogous with Imipenam and Miconazole standard drugs. Carbonic anhydrase-II inhibition of integriside A (1) and B (2) with IC50 value 1.56 µM and 2.85 µM respectively, as compared to standard drug acetazolamide (1.57 µM). Cholinesterase activity was carried out with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) IC50 values of integriside A (1) (8.6, 4.8) and B (2) (0.91, 2.5) were found as compared with standard galanthamine (0.05, 0.92) and Eserine (0.6, 8.7). Here, various molecular descriptors, frontier molecular orbitals (FMO), electron affinity (E.A), ionization potential (IP), molecular electrostatic potential (MEP), and Hirshfeld analysis were carried out to understand the active sites and biological active nature of the integrisides A (1) and B (2). The energy gap, MEP, Hirshfeld analysis, and reactivity descriptors values demonstrate that the integriside A (1) and B (2) retain decent reactivity, which is in good agreement with current experimental and quantum chemical studies.

Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole.

Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = NO3− (1), ClO4− (2)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, 1H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26–0.47 μM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.