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ACS Omega Jun 2024Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can...
Chikungunya virus (CHIKV) has been reported in over 120 countries and is the causative agent of Chikungunya fever. The debilitating nature of this disease, which can persist months to years after acute infection, drastically impacts the quality of life of patients. Yet, specific antivirals are lacking for the treatment of this disease, which makes the search for new drugs necessary. In this context, the nsP2 protease emerges as an attractive therapeutic target, and drug repurposing strategies have proven to be valuable. Therefore, we combined in silico and in vitro methods to identify known drugs as potential CHIKV nsP2 protease inhibitors with antiviral properties within DrugBank. Herein, we developed a hybrid virtual screening pipeline comprising pharmacophore- and target-based screening, drug-like, and pharmaceutical filtering steps. Six virtual hits were obtained, and two of them, capecitabine (CPB) and oxibendazole (OBZ), were evaluated against CHIKV replication in Vero cells. CPB did not present antiviral activity, whereas OBZ inhibited the replication of two different strains of CHIKV, namely, 181-25 (Asian genotype) and BRA/RJ/18 (clinical isolate from ECSA genotype). OBZ showed potent antiviral activity against the CHIKV BRA/RJ/18 (EC = 11.4 μM) with a high selectivity index (>44). Analogs of OBZ (albendazole, fenbendazole, and mebendazole) were also evaluated, but none exhibited anti-CHIKV activity, and further, their stereoelectronic features were analyzed. Additionally, we observed that OBZ acts mainly at post-entry steps. Hence, our results support further in vivo studies to investigate the antiviral potential of OBZ, which offers a new alternative to fight CHIKV infections.
PubMed: 38947813
DOI: 10.1021/acsomega.4c03417 -
Pharmaceuticals (Basel, Switzerland) May 2024Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of...
Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of . In the present study, we describe in detail the direct HPLC resolution of on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water-acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase.
PubMed: 38931363
DOI: 10.3390/ph17060696 -
Transactions of the Royal Society of... Jun 2024We performed a review of published and gray literature of human Hymenolepis diminuta cases across Europe up to July 2022. Of all detectable publications and records, we...
We performed a review of published and gray literature of human Hymenolepis diminuta cases across Europe up to July 2022. Of all detectable publications and records, we further analyzed only those that contained demographic, clinical or epidemiological data regarding the infected subjects. Additionally, one case of hymenolepiasis in a 16-mo-old boy living in the urban part of Belgrade was included in the analysis. Published studies were based in 13/50 European countries and identified 104 laboratory-confirmed cases in total. Almost one-half (49%) of all cases originated from Mediterranean countries. Among symptomatic children, the infection most often manifested with diarrhea, abdominal pain, allergic reaction and behavioral changes. The diagnosis was made by the detection and identification of H. diminuta eggs or parts of strobila in stool samples, although cases of misdiagnosis were also reported. The parasite clearance was established with praziquantel or niclosamide, while the administration of albendazole or mebendazole led to unfavorable results. Future multicentric prospective studies focused on infection screening and the gathering of detailed sociodemographic and clinical data could provide an updated insight into the true distribution and characteristics of H. diminuta infection across Europe.
PubMed: 38864212
DOI: 10.1093/trstmh/trae037 -
BMJ Case Reports Jun 2024Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second...
Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second trimester) in her 20s who presented with 3-day steady epigastric pain radiating to the back and passage of worm from the mouth. She was diagnosed with mild acute pancreatitis, given a significantly elevated serum lipase and absence of organ failures. Fecalysis showed ova; hence, she was treated with mebendazole. Plain MR cholangiopancreatography showed an 842 mL necrotic pancreatic fluid collection and tubular flow void foci within the gallbladder and duodenum consistent with helminthiasis. The patient was managed conservatively in the absence of indications for drainage. The abdominal pain remarkably improved, and she underwent eventual vacuum-assisted delivery to a healthy term baby 4 months after the bout of acute pancreatitis.
Topics: Humans; Female; Ascariasis; Pregnancy; Pancreatitis, Acute Necrotizing; Animals; Ascaris lumbricoides; Pregnancy Complications, Parasitic; Adult; Mebendazole; Abdominal Pain; Cholangiopancreatography, Magnetic Resonance
PubMed: 38862191
DOI: 10.1136/bcr-2024-260316 -
Frontiers in Pharmacology 2024Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact...
Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact kidney function and lead eventually to renal failure. Tolvaptan is the only disease-modifying drug approved for the treatment of ADPKD, however its poor side effect and safety profile necessitates the need for the development of new therapeutics in this area. Using a combination of transcriptomic and machine learning computational drug discovery tools, we predicted that a number of existing drugs could have utility in the treatment of ADPKD, and subsequently validated several of these drug predictions in established models of disease. We determined that the anthelmintic mebendazole was a potent anti-cystic agent in human cellular and models of ADPKD, and is likely acting through the inhibition of microtubule polymerisation and protein kinase activity. These findings demonstrate the utility of combining computational approaches to identify and understand potential new treatments for traditionally underserved rare diseases.
PubMed: 38846086
DOI: 10.3389/fphar.2024.1397864 -
European Journal of Pharmaceutics and... Jul 2024Developing co-amorphous systems is an attractive strategy to improve the dissolution rate of poorly water-soluble drugs. Various co-formers have been investigated....
Developing co-amorphous systems is an attractive strategy to improve the dissolution rate of poorly water-soluble drugs. Various co-formers have been investigated. However, previous studies revealed that it is a challenge to develop satisfied acidic co-formers, e.g., acidic amino acids showed much poorer co-former properties than neutral and basic amino acids. Only a few acidic co-formers have been reported, such as aspartic acid, glutamic acid, and some other organic acids. Thus, this study aims to explore the possibility of adenosine monophosphate and adenosine diphosphate used as acidic co-formers. Mebendazole, celecoxib and tadalafil were used as the model drugs. The drug-co-former co-amorphous systems were prepared via ball milling and confirmed using XRPD. The dissolution study suggested that the solubility and dissolution rate of the drug-co-formers systems were increased significantly compared to the corresponding crystalline and amorphous drugs. The stability study revealed that using the two nucleotides as co-formers enhanced the physical stability of pure amorphous drugs. Molecular interactions were observed in MEB-co-former and TAD-co-former systems and positively affected the pharmaceutical performance of the investigated co-amorphous systems. In conclusion, the two nucleotides could be promising potential acidic co-formers for co-amorphous systems.
Topics: Solubility; Water; Drug Stability; Nucleotides; Celecoxib; Tadalafil; Chemistry, Pharmaceutical; Mebendazole; Drug Liberation
PubMed: 38768766
DOI: 10.1016/j.ejpb.2024.114333 -
Analytical Chemistry May 2024Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T), rarely used in low-field NMR, can be more effective than conventional T and T...
NMR Longitudinal Rotating Frame Relaxation Time (T) with a Weak Spin Locking Field as an Approach to Characterize Solid-State Active Pharmaceutical Ingredients: Proof of Concept.
Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T), rarely used in low-field NMR, can be more effective than conventional T and T relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field () of spinlock pulses. Here, we compared the capacity of T, T, and T to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T and T values of both forms were statistically identical at 0.47 T. Conversely, T of both forms measured with weak spinlock fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T, measured with weak spinlock fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.
Topics: Magnetic Resonance Spectroscopy; Mebendazole; Pharmaceutical Preparations; Magnetic Fields; Proof of Concept Study; Bulk Drugs
PubMed: 38739544
DOI: 10.1021/acs.analchem.3c04935 -
Clinical Case Reports May 2024Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this helminth. Treatment with...
KEY CLINICAL MESSAGE
Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this helminth. Treatment with mebendazole was administered to all family members and it was found that the entire family had been cured.
ABSTRACT
Vulvovaginitis, an inflammation of the vulvovaginal mucous membranes, is a common reason for pediatric gynecology consultations. One of the causes of this condition is a parasitic worm known as (). In girls, adult worms can infiltrate the vagina and release eggs, leading to the development of vulvovaginitis. Furthermore, these worms have the ability to invade the endometrial cavity too. Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by . All members of her family were also infected by this parasitic helminth. In the vaginal sample, apart from the eggs, the female adult worm was observed under the microscope. Treatment with mebendazole was administered to all family members, and their progress was followed for a period of 3 weeks, during which it was found that the entire family had been cured. This patient experienced significant improvement in symptoms related to severe anxiety, nervousness, vaginal inflammation, itching, and vulvovaginitis caused by . To prevent infection by , it is crucial to disinfect underwear and bed sheets. In kindergartens, the spread of this parasite should not be underestimated, and asymptomatic individuals who have been exposed to infected persons should receive treatment to prevent an epidemic. Maintaining cleanliness and hygiene, especially after using the toilet, is of the most importance, particularly for girls who are more susceptible to infection. Additionally, it is essential for all family members to be aware of the transmission routes of this parasite.
PubMed: 38725928
DOI: 10.1002/ccr3.8902 -
Journal of Epidemiology and Global... May 2024Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a...
BACKGROUND
Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a periodic deworming program through the use of single-dose therapy in the endemic regions. Therefore, the purpose of this study was to synthesize evidence about the efficacy of anthelminthic drugs against STH infections among preschool and school-age children.
METHODS
The Preferred Reposting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were followed in this study. Relevant electronic databases, including PubMed, Scopus, Embase, DOAJ, Science Direct, the WHO Clinical Trials.gov library, Google Scholar, and AJOL databases, were searched for relevant publications. Randomized controlled trials (RCTs) and non-randomized interventional studies focused on the efficacy of albendazole and mebendazole against STHs in children were included in the study. Review Manager was used to analyze the data. A random effects model was used to obtain the pooled estimated efficacy. To evaluate heterogeneity, the I test and Cochrane Q (χ) were employed. The risk of publication bias was investigated using Egger's test and the funnel plot. The protocol of this review was registered at the PROSPERO international prospective register of systematic reviews (CRD42023401196).
RESULTS
Of the 69 publications selected for the systematic review, 66 with complete data were included in the meta-analysis. Single doses of albendazole and mebendazole have shown satisfactory efficacy [egg reduction rate (ERR)] against Ascaris lumbricoides [95.54% (95% CI: 88.75-102.34%) and 98.69% (95% CI: 97.68-99.65%), respectively. The effectiveness of these two drugs against Trichuris trichiura and hookworms was comparatively low (< 80% ERR), except for albendazole, which showed high ERRs [93.44% (95%CI: 92.39-94.49%)] against hookworms. The cure rate (CR) of albendazole against T. trichiura, A. lumbricoides, and hookworms were 50.8%, 91.3%, and 78.32%, respectively. Likewise, mebendazole showed CRs of 48.15%, 92.8%, and 49.32% against T. trichiura, A. lumbricoides, and hookworms, respectively. Subgroups such as studies conducted after 2000, diagnostic type (McMaster), and longer follow-up weeks significantly reduced the efficacy of the two drugs against T. trichura. While the combination of albendazole or mebendazole with other drugs and RCT showed significantly improved efficacy against T. trichura. The count of eggs per gram of stool (EPG) was identified as one of the variables that negatively and significantly influenced the efficacy of albendazole or mebendazole against A. lumbricoides.
CONCLUSION
Despite the wide range of ERRs and CR reported in the different articles included in this review, the pooled estimated efficacy of albendazole and mebendazole against STHs falls in the satisfactory category of WHO recommendations. Further evaluation of the combination of anthelminthic drugs as a preventive chemotherapy option and routine drug efficacy testing are necessary to prevent the emergence and widespread use of drug-resistant STHs.
PubMed: 38696109
DOI: 10.1007/s44197-024-00231-7 -
BMC Women's Health Apr 2024Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making...
BACKGROUND
Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making their caretakers a population at risk for the transmission of this helminth. It can occasionally affect extraintestinal organs and tissues, including the female genital tract. Infestation can be asymptomatic or manifest as different kinds of gynaecological disorders, such as pelvic inflammation mimicking tumours, abnormal uterine bleeding, or vaginitis. Diagnosis is made by identifying ova in the sample collected from the perineal skin using a transparent adhesive tape or microscopic examination of resected tissue. Mebendazole is the first-line medication and should also be administered to all household members.
CASE PRESENTATION
We present a case of a patient who had undergone surgery for invasive cervical cancer with an accidental finding of E. vermicularis eggs in the cervix.
CONCLUSIONS
Although not very common, infestation with E. vermicularis should be considered in differential diagnoses of various gynaecological disorders accompanied by histological findings of granulomatous inflammation.
Topics: Humans; Female; Enterobiasis; Uterine Cervical Neoplasms; Enterobius; Animals; Mebendazole; Cervix Uteri; Diagnosis, Differential; Middle Aged; Adult
PubMed: 38678281
DOI: 10.1186/s12905-024-03073-4