Glutathione-Conjugated Fluorometric Ratiometric NIR-Silicon Nanoparticles and Its Applications for In Vitro and In Vivo Imaging.

Glutathione (GSH), a tripeptide molecule, is the most abundant nonprotein biothiol in living cells, playing a crucial role in preventing oxidative damage to cellular components and maintaining intracellular redox homeostasis. As a thiol molecule, GSH contains a sulfhydryl (-SH) group that is vital for the body's response to reactive oxygen species (ROS). To confirm whether GSH can be used as a bioindicator or in the early diagnosis of cancers at the cellular level, it is essential to achieve highly selective detection and conjugation of GSH to silicon nanoparticles (SiNPs) under pathological conditions. We are herein excited to report a type of fluorescent ratiometric near-infrared silicon nanoparticle (NIR-SiNP) probe, that is, glutathione peptide conjugated (NIR-SiNPs-GSH), which simultaneously possess small pore sizes at an average of 6.7 nm, an emission of 670 nm, a bioimaging functionality of living cancer cells and animals, and favorable biocompatibility. Taking advantage of these virtues, we further manifest that such resulting NIR-SiNPs, NIR-SiNPs-GSH bioprobes are marvelously worthy for immunofluorescence imaging of cancer cells and living mice. Furthermore, it was shown that DAPI and probes could selectively stain malignant tumor cell nuclei, indicating the possibility for bioimaging and identification of cancer cells and animals. In summary, the suggested NIR-SiNPs-GSH probe has the potential to be a very effective chemical tool for early tumor detection in the future.

A novel mucoadhesive paliperidone-nanoemulsion developed using the ultrasonication method in the treatment of schizophrenia.

Aim: To develop paliperidone mucoadhesive-nanoemulsion (PLP-NE) to enhance brain bioavailability. To evaluate comparative effects of PLP-NE and CS-PLP-NE in the treatment of schizophrenia, followed by a toxicity study of opt-NE. Material and methods: Oil: oleic acid, surfactant: Tween-80, and co-surfactant: Labrasol were chosen based on the solubility and maximum nanoemulsion area. The ultrasonication technique was applied with the aqueous micro titration method for the development of PLP-NE. The optimization of the method for the excellent PLP-NE was performed using a central composite design based on a five-factor and four-level. Oil (% v/v), S mix (v/v%), ultrasonication intensity in percentage, ultrasonication time in minutes, and temperature (°C) were optimized and used to the independent variables. Results: The parameters i.e., oil (5%), S mix (10%), ultrasonication time (5.0 min), ultrasonication intensity (25%), and temperature (38 °C) were optimized and used as independent and dependent variables for the development of novel PLP-NE. Based on experimental data, the dependent variables, i.e., globule size (53.90 ± 4.01 nm), % transmittance (92.56% ± 1.06%), PDI (0.218 ± 0.007), and zeta potential (-11.60 ± 0.031 mV), were determined. The smooth near about spherical shaped of PLP-NE globules with, refractive index i.e., 1.62 ± 0.021, viscosity: 39 ± 6 cp with the pH: 7.40 ± 0.089, and content of drug (97.98 ± 0.39%) for optimized-PLP-NE. The optimized PLP-NE with oleic acid, Tween-80, and Labrasol was used to improve brain bioavailability with good permeation via the intranasal route. CS-PLP-NE yielded good mucoadhesive property results compared to paliperidone-nanoemulsion, and PLP-S containing a 0.751 minutes retention time with their deuterated-IS (0.806 min) and m/z of 427.2/207.2 with IS (m/z: 431.2/211.2) for PLP and PLP-IS. A calibration curve was plotted with a linear range of 1-2000 ng mL-1 with inter- and intraday accuracy (97.03-99.31%) and precision (1.69-50.05%). The results of AUC(0-24) and C max for PLP were found to be highly significant (p < 0.001) as an improvement of brain bioavailability in rats via intranasal delivery of CS-PLP-NE. Furthermore, the locomotion test, social interaction, and forced swimming test (forced swimming, climbing, and immobility) of a mucoadhesive CS-PLP-NE (intranasally) provided highly significant results with the improvement of behavioral analysis when compared to the PLP-NE and PLP-S studies. Conclusion: CS-PLP-NE (i.n.) showed highly significant results, i.e., p < 0.001 for the improvement of bioavailability of the brain in the treatment of schizophrenia. Optimized-mucoadhesive-CS-based-PLP-NE is safe and shows no toxicity.

Anti-Acanthamoebic effects of silver-conjugated tetrazole nanoparticle.

Tetrazoles are five-membered ring aromatic heterocyclic molecules that consist of one carbon and four nitrogen atoms. Several tetrazole-based drugs have shown promising activities against bacteria, fungi, asthma, cancer, hypertension etc. The overall aim of this study was to determine anti-Acanthamoebic properties of tetrazoles and tetrazole-conjugated silver nanoparticles. Tetrazole-conjugated silver nanoparticles were synthesized and confirmed using ultraviolet-visible spectrometry, Dynamic light scattering, and Fourier-transform infrared spectroscopy. Using amoebicidal, encystment, and excystment assays, the findings revealed that tetrazoles exhibited antiamoebic properties and these effects were enhanced when conjugated with silver nanoparticles. Importantly, conjugation with silver nanoparticles inhibited parasite-mediated human cell death in vitro, as measured by lactate dehydrogenase release, but it reduced toxic effects of drugs alone on human cells. Overall, these results showed clearly that tetrazoles exhibit potent antiamoebic properties which can be enhanced by conjugation with silver nanoparticles and these potential in the rational development of therapeutic interventions against parasitic infections such as keratitis and granulomatous amoebic encephalitis due to pathogenic Acanthamoeba.

Seasonal variations and social disparities in asthma hospitalizations and outcomes.

OBJECTIVE: Exposure to asthma exacerbating triggers may be dependent on the season and an individual's social factors and subsequent means to avoid triggers. We assessed for seasonal variations and differential outcomes based on race and income in admissions for asthma in a United States nationwide assessment. METHODS: This retrospective study assessed adult hospitalizations for asthma 2016-2019 using the National Inpatient Sample. Hospitalizations were categorized by season: winter (December-February), spring (March-May), summer (June-August), fall (September-November). Multivariable linear and logistic regression were used to assess associations between season, race, income quartile (determined by the median income within a patient's ZIP code), and outcomes. RESULTS: The study included 423,140 admissions with a mean age of 51 years, and 73% of the cohort being female and 56% non-white. Admissions peaked during winter (124, 145) and were lowest in summer (80,525). Intubation rates were increased in summer compared to winter (2.73 vs 1.93%, aOR = 1.19, 95% CI: 1.04-1.37) as were rates of noninvasive positive pressure ventilation (NIPPV) (7.92 vs 7.06%, aOR = 1.08, 95% CI: 1.00-1.17). Compared to white patients, intubation (2.53 vs 1.87%, absolute difference 0.66%, aOR = 1.14, 95% CI: 1.02-1.29) and NIPPV (9.95 vs 5.45%, absolute difference 4.5%, aOR = 1.69, 95% CI: 1.57-1.82) were increased in Black patients. No significant associations between income and clinical outcomes were found. CONCLUSIONS: Asthma admission peak during winter, while summer admissions and non-white race are associated with higher rates of NIPPV and intubation. Public health initiatives and strategically timed outpatient visits could combat seasonal variation and social disparities in asthma outcomes.

Problems in Commercial Kits of 25-Hydroxy Vitamin D and the Development of Simple, Robust and Faster HPLC Method.

Vitamin D is a lipid-soluble compound that plays a key role in bone mineral metabolism. The commercial current kits and several published assay methods (High-performance liquid chromatography (HPLC) and Immunoassay) are complicated due to the use of multiple reagents, larger sample volume, high backpressure, longer extraction time, evaporation under nitrogen after extraction, significant interference and antibody cross-reactivity. Here we report a new HPLC method for the determination of 25-hydroxyvitamin D2 (25-OHD2) and 25-hydroxyvitamin D3 (25-OHD3) that is simple (no evaporation), rapid (10-minute run time) and robust. Serum sample (300 µl) is mixed with 300 µl acetonitrile containing lauraphenone as internal standard. After vortexing and centrifugation, the supernatant was loaded into C18 extraction cartridges, washed with 70% methanol and then eluted with 200 µl of a mixture of 70% ethanol and 30% isopropyl alcohol (IPA). The eluent was mixed with 50 µl of water and injected into the HPLC-UV system for analysis. The method proved to be linear in the range of 10-750 nmol/L of 25-OHD2 and 25-OHD3. The intra- and inter-assay precision was less than 10 for both compounds at four different concentrations. The method was compared with (LC-MS/MS) and the correlation coefficients (R2) were 0.9454 and 0.9673 for 25-OHD2 and 25-OHD3 respectively. The proposed HPLC method is simple, rapid, robust and free from the most common problems encountered with commercial kits. It can be used in a high-volume laboratory that uses the HPLC method for the simultaneous determination of 25-OHD2 and 25-OHD3 in serum samples.

Occupational hazard in urolithiasis patients in Qatar: A single-center cross-sectional study.

BACKGROUND: Urolithiasis is one of the most prevalent urological diseases and is associated with a substantial economic burden. Its prevalence varies according to geographical location. Qatar is a Middle Eastern country located in the Afro-Asian Stone Belt. It has a dry and hot climate, which may predispose individuals working in these environments to form kidney stones (KSs). METHODS: A population sample of 4204 patients was categorized into five occupational classes. The frequencies and correlations of these occupations with KS formation were calculated. RESULTS: Among the total cases, 2000 presented with KSs, with the majority being of Asian descent (49%), followed by individuals of Middle Eastern descent (35.1%). Technicians accounted for 35.15% of KS cases followed by clerks (29.2%) and executives (14.6%). Among KS cases, 44% had a single stone, 30% had multiple stones, and 26% had two stones. In comparing both KS and non-KS groups, age, gender, occupation, and race were significantly associated with KS formation (p<0.05), while BMI did not show any significant correlation (p>0.05). Asian males aged 31-40, working as technicians, were significantly more prone to urolithiasis. In comparing age, BMI, and gender with stone characteristics, only age was found significantly associated with stone size (p<0.05). Occupation showed an impact on all studied stone characteristics. Clerks and technicians presented more frequently with stones within the 11-15 mm range, while executives more frequently presented with smaller stones (p<0.001). Stone density was more frequently <500 HU in workers, technicians and housewives and >500 HU in executives and clerks (p<0.001). CONCLUSIONS: Our findings revealed an elevated risk of urolithiasis among certain occupational groups, particularly technicians, who frequently work outdoors in high-temperature environments. Alternatively, the sedentary nature of clerical and executive positions can also contribute to the risk of urolithiasis.

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

Cytoreductive therapy in younger adults with polycythemia vera: a meta-analysis of safety and outcomes.

ABSTRACT: Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.

Can non-invasive cardiac hemodynamics and fluid content system (NICaS) parameters predict Acute Heart Failure outcomes in Caucasian and Asian patients in the emergency department?

PURPOSE: Acute heart failure (AHF) is a serious condition that requires prompt diagnosis and management. To optimize patient care, clinicians need a reliable, non-invasive method to assess hemodynamic parameters and total body congestion. Currently, no standardized technology is widely used for this purpose. However, NICaS technology, which measures hemodynamic parameters based on regional bioimpedance, has shown promise in monitoring AHF patients in a non-invasive and reliable manner. In this study, researchers aimed to evaluate the usefulness of NICaS technology in predicting patients' outcome in Caucasian and Asian AHF patients presenting to the emergency department (ED). PATIENTS AND METHODS: The study included 40 Caucasian patients from Italy (group A) and 71 Asian patients from Indonesia and Singapore (group B) with a diagnosis of AHF in the ED. The study compared data from NICaS parameters, clinical findings, laboratory, and radiological results with short-term events. RESULTS: In group A, NICaS data at ED arrival significantly predicted 30-day cardiovascular mortality and rehospitalization. At discharge, a value of cardiac output obtained using NICaS was a significant predictor for 30-day rehospitalization. In group B, NICaS variables, total peripheral resistance index on admission and during 48-72 â€‹h had prominent AUC compared to clinical congestion score and NT-proBNP in predicting mortality and rehospitalization. CONCLUSIONS: The results indicate that NICaS technology offers a simple, non-invasive, and reliable method of assessing cardiac hemodynamics and congestion in AHF patients. These measurements may enhance diagnosis, tailor management plans, stratify risk, and predict outcomes in both Caucasian and Asian patients.

In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives.

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Association between asthma and periodontitis.

The association between asthma and periodontitis is of interest. 20 periodontitis patients with asthma (asthma group) and 20 patients without asthma (non-asthma group) were included based on inclusion and inclusion criteria. Periodontitis was classified according to 2017 periodontal classification and periodontal parameters such as tooth loss, pocket depth, clinical attachment loss, alveolar bone loss, bone reduction index, plaque index, bleeding index and periodontal risk were assessed. Effect of anti-asthmatic drugs and asthma control on periodontal parameters was also assessed. Inter-group comparison of all the continuous variables was done using independent "t" test. Comparison of categorical variables was done using Chi-square test. P value <0.05 was considered statistically significant. Results showed greater severity and higher grade of periodontitis with asthma group as well as with patients on anti-asthmatic drugs and patients with poor controlled asthma. Hence, there is an association between asthma and periodontitis.

Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.

Unsymmetrical thiourea derivatives: synthesis and evaluation as promising antioxidant and enzyme inhibitors.

Background: Unsymmetrical thioureas 1-20 were synthesized and then characterized by various spectroscopy techniques such as UV, IR, fast atom bombardment (FAB)-MS, high-resolution FAB-MS, 1H-NMR and 13C-NMR. Methods: Synthetic compounds 1-20 were tested for their ability for antioxidant, lipoxygenase and xanthine oxidase activities. Results: Compounds 1, 2, 9, 12 and 15 exhibited strong antioxidant potential, whereas compounds 1-3, 9, 12, 15 and 19 showed good to moderate lipoxygenase activity. Ten compounds demonstrated moderate xanthine oxidase inhibition. Conclusion: Compound 15 displayed the highest potency among the series, exhibiting good antioxidant, lipoxygenase and xanthine oxidase activities. Theoretical calculations using density functional theory and molecular docking studies supported the experimental findings, indicating the potential of the synthesized compounds as potent antioxidants, lipoxygenases and xanthine oxidase agents.

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.

Accurate determination of Biotinidase activity in serum by HPLC and its utilization as second tier test for the confirmation of initial positive newborn screening results.

Diagnosis of Biotinidase deficiency (BTD) is extremely important to avoid several neurodevelopmental problems in early childhood. Colorimetric and fluorometric methods lack specificity and selectivity due to several interferences resulting in a high number of false positive results. We developed an HPLC method for BTD activity in serum with fluorescent detection. In colorimetric assays, biotinidase attacks the amide linkage of the artificial substrate biotinidyl-4-aminobenzoic acid (B-PABA) and releases p-aminobenzoic acid (PABA), which is converted to a purple dye by diazotization reaction. The newly developed method injects the reaction mixture directly into the HPLC column and quantifies using a six-point calibration curve without coupling and diazotization reaction. The method is linear over the 5-1000 µmol/L range. The detection and quantitation limits were 2.5 µmol/L and 5.0 µmol/L, respectively. When compared with colorimetric assay, the correlation coefficient (R2) was 0.9963. The within-assay and between-assay precision was <10.0% for four levels of quality control samples. No significant variation in BTD activity was detected due to hemolysis, icteric, and lipemic samples. The newly developed method eliminates the potential interference due to the presence of aromatic amines and significantly reduces the false positive results observed with the colorimetric method. It is simple, specific, sensitive, faster in sample preparation, and requires a small sample volume. The newly developed HPLC method was used in our laboratory as a secondary tier test for initial positive BTD samples from newborn screening programs. To our knowledge, no similar HPLC method has been reported to date.

Indenoquinoxaline-phenylacrylohydrazide hybrids as promising drug candidates for the treatment of type 2 diabetes: In vitro and in silico evaluation of enzyme inhibition and antioxidant activity.

Existing drugs that are being used to treat type-2 diabetes mellitus are associated with several side effects; thus, exploring potential drug candidates is still an utter need these days. Hybrids of indenoquinoxaline and hydrazide have never been explored as antidiabetic agents. In this study, a series of new indenoquinoxaline-phenylacrylohydrazide hybrids (1-30) were synthesized, structurally characterized, and evaluated for α-amylase and α-glucosidase inhibitory activities, as well as for their antioxidant properties. All scaffolds exhibited varying degrees of inhibitory activity against both enzymes, with IC50 values ranging from 2.34 to 61.12 µM for α-amylase and 0.42 to 54.72 µM for α-glucosidase. Particularly, compounds 10, 16, 17, 18, 24, and 25 demonstrated the highest efficacy in inhibiting α-amylase, while compounds 6, 7, 8, 10, 12, 14, 13, 16, 17, 18, 24, and 25 were the most effective α-glucosidase inhibitors, compared to standard acarbose. Moreover, most of these compounds displayed substantial antioxidant potential compared to standard butylated hydroxytoluene (BHT). Kinetics studies revealed competitive inhibition modes by compounds. Furthermore, a comprehensive in silico study and toxicity prediction were also conducted, further validating these analogs as potential drug candidates. The structured compounds demonstrated enhanced profiles, underscoring their potential as primary candidates in drug discovery.

Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.

The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.