Core Soil Microorganisms and Abiotic Properties as Key Mechanisms of Complementary Nanoscale Zerovalent Iron and Nitrification Inhibitors in Decreasing Paclobutrazol Residues and Nitrous Oxide Emissions.

Agrochemical residues and nitrous oxide (N2O) emissions have caused considerable threats to agricultural soil ecology. Nanoscale zerovalent iron (nZVI) and nitrification inhibitors might be complementary to each other to diminish soil agrochemical residues and N2O emissions and enhance soil bacterial community diversities. Compared to the control, the nZVI application declined soil paclobutrazol residues by 5.9% but also decreased the bacterial community co-occurrence network node. Combined nZVI and Dicyandiamide applications significantly decreased soil N2O emission rates and paclobutrazol residues but promoted Shannon diversity of the bacterial community. The increased soil pH, ammonium nitrogen, and Actinobacteriota could promote soil paclobutrazol dissipation. The nZVI generated double-edged sword effects of positively decreasing paclobutrazol residues and N2O emissions but negatively influencing soil multifunctionalities. The nZVI and Dicyandiamide could be complementary to each other in diminishing soil agrochemical residues and N2O emission rates but promoting soil bacterial community diversities simultaneously.

The impact of chelation compliance in health outcome and health related quality of life in thalassaemia patients: a systematic review.

Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.

Genotoxic effects induced by iprodione and tebuconazole in meristematic cells of Allium cepa: responses dependent on concentration and exposure time.

The present work explores the genotoxicity of the fungicides iprodione (IP) and tebuconazole (TB) using the Allium cepa assay as an in vivo biological model. Both short-term and long-term exposures were studied, revealing concentration- and time-dependent cytological and genotoxic effects. IP exhibited genotoxicity over a wider concentration range (5-50 µg/ml) and required 30 h of exposure, while TB showed genotoxicity at higher concentrations (10 and 30 µg/ml) within a 4-h exposure period. The study highlights the importance of assessing potential risks associated with fungicide exposure, including handling, disposal practices, and concerns regarding food residue. Moreover, the research underscores the genotoxic effects of IP and TB on plant cells and provides valuable insights into their concentration and time-response patterns.

Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.

Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild to Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial.

Importance: Treatment options for COVID-19 are warranted irrespective of the presence of risk factors for severe disease. Objective: To assess the efficacy and safety of ensitrelvir in patients with mild to moderate COVID-19. Design, Setting, and Participants: This phase 3 part of a phase 2/3, double-blind, placebo-controlled randomized clinical trial was conducted from February 10 to July 10, 2022, with a 28-day follow-up period, at 92 institutions in Japan, Vietnam, and South Korea. Patients (aged 12 to <70 years) with mild to moderate COVID-19 within 120 hours of positive viral test results were studied. Interventions: Patients were randomized (1:1:1) to receive 125 mg of once-daily ensitrelvir (375 mg on day 1), 250 mg of once-daily ensitrelvir (750 mg on day 1), or placebo for 5 days. Main Outcomes and Measures: The primary end point was the time to resolution of the composite of 5 characteristic symptoms of SARS-CoV-2 Omicron infection, assessed using a Peto-Prentice generalized Wilcoxon test stratified by vaccination history. Virologic efficacy and safety were also assessed. Results: A total of 1821 patients were randomized, of whom 1030 (347 in the 125-mg ensitrelvir group, 340 in the 250-mg ensitrelvir group, and 343 in the placebo group) were randomized in less than 72 hours of disease onset (primary analysis population). The mean (SD) age in this population was 35.2 (12.3) years, and 552 (53.6%) were men. A significant difference was observed between the 125-mg ensitrelvir group and the placebo group (P = .04 with a Peto-Prentice generalized Wilcoxon test). The difference in median time was approximately 1 day between the 125-mg ensitrelvir group and the placebo group (167.9 vs 192.2 hours; difference, -24.3 hours; 95% CI, -78.7 to 11.7 hours). Adverse events were observed in 267 of 604 patients (44.2%) in the 125-mg ensitrelvir group, 321 of 599 patients (53.6%) in the 250-mg ensitrelvir group, and 150 of 605 patients (24.8%) in the placebo group, which included a decrease in high-density lipoprotein level (188 [31.1%] in the 125-mg ensitrelvir group, 231 [38.6%] in the 250-mg ensitrelvir group, and 23 [3.8%] in the placebo group). No treatment-related serious adverse events were reported. Conclusions and Relevance: In this randomized clinical trial, 125-mg ensitrelvir treatment reduced the time to resolution of the 5 typical COVID-19 symptoms compared with placebo in patients treated in less than 72 hours of disease onset; the absolute difference in median time to resolution was approximately 1 day. Ensitrelvir demonstrated clinical and antiviral efficacy without new safety concerns. Generalizability to populations outside Asia should be confirmed. Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT2031210350.

Design, synthesis, and bioactivity studies of chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine.

In this study, 30 chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine were designed and synthesized. The results of antibacterial activity showed that EC50 values of N26 against Xoo, Pcb was 36.41, 38.53 µg/mL, respectively, which were better than those of thiodiazole copper, whose EC50 values were 60.62, 106.75 µg/mL, respectively. The bacterial inhibitory activity of N26 against Xoo was verified by SEM. Antibacterial mechanism between N26 and Xoo was preliminarily explored, the experimental results showed that when the drug concentration was 100 mg/L, N26 had a good cell membrane permeability of Xoo, and it can inhibit the production of EPS content and extracellular enzyme content to disrupt the integrity of the Xoo biofilms achieving the effect of inhibiting Xoo. At 200 mg/L, N26 can protect and inhibit the lesions of post-harvested potatoes in vivo. The activities of N1-N30 against TMV were determined with half leaf dry spot method. The EC50 values of the curative and protective activity of N22 was 77.64 and 81.55 µg/mL, respectively, which were superior to those of NNM (294.27, 175.88 µg/mL, respectively). MST experiments demonstrated that N22 (Kd = 0.0076 ± 0.0007 µmol/L) had a stronger binding ability with TMV-CP, which was much higher than that of NNM (Kd = 0.7372 ± 0.2138 µmol/L). Molecular docking results showed that N22 had a significantly higher affinity with TMV-CP than NNM.

Effects on hearing after long-term use of iron chelators in beta-thalassemia: Over twenty years of longitudinal follow-up.

OBJECTIVE: The role of iron chelation in causing hearing loss (HL) is still unclear. The present study assessed the prevalence of HL among transfusion-dependent thalassemia (TDT) patients who underwent audiological follow-up over a 20-year period. METHODS: We retrospectively analyzed clinical records and audiological tests from January 1990 (T0) to December 2022 (T22) of a group of TDT patients who received iron chelation therapy with deferoxamine (DFO), deferiprone (DFP) or deferasirox (DFX), in monotherapy or as part of combination therapy. RESULTS: A total of 42 adult TDT patients (18 male, 24 female; age range: 41-55 years; mean age: 49.2 ± 3.7 years) were included in the study. At the T22 assessment, the overall prevalence of sensorineural HL was 23.8 % (10/42). When patients were stratified into two groups, with and without ototoxicity, no differences were observed for sex, age, BMI, creatinine level, pre-transfusional hemoglobin, start of transfusions, cardiac or hepatic T2 MRI; only ferritin serum values and duration of chelation were significantly higher (p = 0.02 and p = 0.01, respectively) in patients with hearing impairment in comparison to those with normal hearing. CONCLUSION: This study with long-term follow-up suggests that iron chelation therapy might induce ototoxicity; therefore, a long and accurate audiological follow-up should be performed in TDT patients.

Determination of chiral prothioconazole and its chiral metabolite in water, juice, tea, and vinegar using emulsive liquid-liquid microextraction combined with ultra-high performance liquid chromatography.

Emulsive liquid-liquid microextraction (ELLME), a simple, rapid, and environmentally friendly technique, was established to identify chiral prothioconazole and its chiral metabolite in water, juice, tea, and vinegar using ultra-high-performance liquid chromatography (UPLC). Environmentally friendly extractant was mixed with pure water to prepare a high-concentration emulsion, which was added to samples to complete the emulsification and extraction in 1 s. Afterward, an electrolyte solution was added to complete the demulsification without centrifugation. ELLME did not use dispersants compared to the familiar dispersive liquid-liquid microextraction (DLLME), thus reducing the use of toxic solvents and avoiding the effect of dispersants on the partition coefficient. The linear range was from 0.01 to 1 mg/L. The limit of detection was 0.003 mg/L. The extraction recoveries ranged from 82.4 % to 101.6 %, with relative standard deviations of 0.7-5.2 %. The ELLME method developed has the potential to serve as an alternative to DLLME.

Combination chelation therapy.

Combination chelation therapies are considered in transfusion-dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real-life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies.

Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections.

Millions who live in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections, which cause Chagas disease and human African trypanosomiasis (HAT). Improved HAT treatments are available, but Chagas disease therapies rely on two nitroheterocycles, which suffer from lengthy drug regimens and safety concerns that cause frequent treatment discontinuation. We performed phenotypic screening against trypanosomes and identified a class of cyanotriazoles (CTs) with potent trypanocidal activity both in vitro and in mouse models of Chagas disease and HAT. Cryo-electron microscopy approaches confirmed that CT compounds acted through selective, irreversible inhibition of trypanosomal topoisomerase II by stabilizing double-stranded DNA:enzyme cleavage complexes. These findings suggest a potential approach toward successful therapeutics for the treatment of Chagas disease.

Ovulation induction with letrozole and dexamethasone in infertile patients with letrozole-resistant polycystic ovary syndrome.

PURPOSE: To assess efficacy of adjuvant dexamethasone during letrozole cycles for ovulation induction (OI) in women with letrozole-resistant polycystic ovary syndrome (PCOS). METHODS: We retrospectively evaluated 42 cycles of OI from 28 infertile women with letrozole-resistant PCOS between September 2019 and November 2022. Letrozole was initiated on cycle day 3 for 5 days and increased via a stair-step approach to 7.5 mg as indicated. Patients were deemed letrozole-resistant if no dominant follicle was identified on transvaginal ultrasound following this dose. Resistant patients then received 5 additional days of letrozole 7.5 mg with low-dose dexamethasone 0.5 mg for 7 days and had a repeat ultrasound. The primary outcome was ovulation rate determined by the presence of a dominant follicle on ultrasound. Secondary outcomes included endometrial thickness, number of measurable follicles, and pregnancy outcomes among responders. RESULTS: Twenty-two of 28 (79%) letrozole-resistant PCOS patients had evidence of ovulation after the addition of dexamethasone in 35 out of 42 (83%) cycles. Clinical pregnancy occurred in 20% of ovulatory cycles with a cumulative rate of 32%. All clinical pregnancies resulted in a live birth. Patients who responded to adjuvant dexamethasone were more likely to have a shorter duration of infertility; however, there were no differences in other demographics, serum androgens including DHEA-S, or pretreatment glycemic status. CONCLUSION: Adding dexamethasone to letrozole increased ovulation rates in letrozole-resistant PCOS patients undergoing OI with similar pregnancy outcomes to prior studies. The addition of dexamethasone is an effective, inexpensive, and safe option for PCOS patients otherwise at risk for cycle cancelation.

Nephrolithiasis in two patients on iron chelation therapy: A case report.

Drug-induced nephrolithiasis can arise from insoluble components within medications or crystallization of metabolites due to changes in metabolism and urinary pH. The connection between drugs utilized for iron chelation therapy (ICT) and nephrolithiasis is not well understood. In this report, we describe two pediatric patients diagnosed with nephrolithiasis while undergoing treatment with the chelating agents deferasirox, deferiprone, and deferoxamine for iron overload secondary to repeat blood transfusion.

[QuEChERS-liquid chromatography-tandem mass spectrometry for determination of 22 triazole pesticide residues in Chinese herbal medicines].

Eight well-known herbals in Zhejiang Province, Zhebawei, are commonly used as traditional Chinese herbal medicines owing to their rich active ingredients. However, the unavoidable use of pesticides during agricultural production has led to pesticide residue problems in these herbs. In this study, a simple, rapid, and accurate method was established to determine 22 triazole pesticide residues in Zhebawei. An improved QuEChERS method was used for sample pretreatment, and Rhizoma Atractylodis Macrocephalae was used as a representative sample. The sample was extracted with acetonitrile to eliminate some polar and nonpolar compounds, pigments, and other impurities, and the purification effects of multiwalled carbon nanotubes (MWCNTs), amino-modified multiwalled carbon nanotubes (MWCNTs-NH2), carboxylated multiwalled carbon nanotubes (MWCNTs-COOH), crosslinked polyvinylpyrrolidone (PVPP), zirconium dioxide (ZrO2), 3-(N,N-diethylamino)-propyltrimethoxysilane (PSA), octadecyl (C18), and graphitized carbon black (GCB) were compared. MWCNTs-COOH and C18 were selected as the purification adsorbents, and their dosages were systematically optimized. The combination of 10 mg of MWCNTs-COOH and 20 mg of C18 was eventually selected as the purification adsorbents. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis, and box graphs were plotted to present the dispersion of each group of recoveries, thus enabling the identification of the data outliers, dispersion distribution, and data symmetry. The established method was systematically verified and showed good linearity over the concentration range of 1-200 µg/L (except for bromuconazole, epoxiconazole, and etaconazole) with correlation coefficients >0.99. The average recoveries of the 22 pesticides at spiked levels of 10, 20, 100, and 200 µg/kg were in the range of 77.0%-115% with relative standard deviations (RSDs) <9.4%. The limits of detection and quantification were 1-2.5 µg/kg and 10-20 µg/kg, respectively. The applicability of the developed method to other herbals was investigated at 100 µg/kg, and the average recoveries of the target pesticides in different matrices ranged from 76.4% to 123% with RSDs <12.2%. Finally, the method established was used to detect triazole pesticide residues in 30 actual Zhebawei samples. The results showed that triazole pesticides were present in Bulbus Fritillariae Thunbergii and Dendranthema Morifolium. Difenoconazole was detected in Bulbus Fritillariae Thunbergii at contents ranging from 41.4 µg/kg to 110 µg/kg, while difenoconazole, myclobutanil, triadimenol and propiconazole were detected in Dendranthema Morifolium at contents ranging from 16.1 µg/kg to 250 µg/kg. The established method can meet the requirements for the accurate quantitative analysis of triazole fungicides in Zhebawei.

Vacuum-assisted thermal bonding of ß-cyclodextrin and its derivatives as chiral stationary phases for high-performance liquid chromatography.

In this work, the vacuum-assisted thermal bonding method was proposed for the covalent coupling of ß-cyclodextrin (ß-CD) (CD-CSP), hexamethylene diisocyanate cross-linked ß-CD (HDI-CSP) and 3, 5-dimethylphenyl isocyanate modified ß-CD (DMPI-CSP) onto the isocyanate silane modified silica gel. Under vacuum conditions, the side reaction due to the water residue from the organic solvent, air, reaction vessels and silica gel could be avoided, and the optimal temperature and time of vacuum-assisted thermal bonding method were determined as 160°C and 3 h. These three CSPs were characterized by FT-IR, TGA, elemental analysis and the nitrogen adsorption-desorption isotherms. The surface coverage of CD-CSP and HDI-CSP on silica gel was determined as ∼0.2 µmol m-2, respectively. The chromatographic performances of these three CSPs were systematically evaluated by separating 7 flavanones, 9 triazoles and 6 chiral alcohols enantiomers under the reversed-phase condition. It was found that the chiral resolution ability of CD-CSP, HDI-CSP and DMPI-CSP was complementary to each other. Among them, CD-CSP could separate all 7 flavanones enantiomers with the resolution of 1.09-2.48. HDI-CSP had a good separation performance for triazoles enantiomers with one chiral center. DMPI-CSP showed excellent separation performance for chiral alcohol enantiomers, among which the resolution of trans-1, 3-diphenyl-2-propen-1-ol reached 12.01. Generally, the vacuum-assisted thermal bonding had been demonstrated as a direct and efficient method for the preparation of chiral stationary phases of ß-CD and its derivatives.

Iron chelation therapy.

Iron overload is a pathological condition resulting from a congenital impairment of its regulation, increased intestinal iron absorption secondary to bone marrow erythroid hyperplasia, or a chronic transfusional regimen. In normal conditions, intracellular and systemic mechanisms contribute to maintaining iron balance. When this complex homeostatic mechanism fails, an iron overload could be present. Detecting an iron overload is not easy. The gold standard remains the liver biopsy, even if it is invasive and dangerous. Identifying iron using noninvasive techniques allowed a better understanding of the rate of iron overload in different organs, with a low risk for the patient. Estimating serum ferritin (mg/L) is the easiest and, consequently, the most employed diagnostic tool for assessing body iron stores, even if it could be a not specific method. The most common hematological causes of iron overload are myelodysplastic syndromes, sickle cell disease, and thalassemia. In all of these conditions, three drugs have been approved for the treatment of iron overload: deferiprone, deferoxamine, and deferasirox. These chelators have been demonstrated to help lower tissue iron levels and prevent iron overload complications, improving event-free survival (EFS). Nowadays, the decision to start chelation and which chelator to choose remains the joint decision of the clinician and patient.

Health economic analysis of patients treated with isavuconazole in a German comprehensive cancer centre.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening and demand timely and appropriate treatment. Research showed that isavuconazole treatment positively affects clinical outcome and length of hospital stay (LOS). OBJECTIVES: The aim of this study was to assess the hospital costs of patients diagnosed with IFD and treated with isavuconazole using real-world data from a German cancer centre. PATIENTS/METHODS: Data and LOS collected from Jan-2016 to Jun-2021 at Department I of Internal Medicine, University Hospital Cologne were retrieved. Case-related resources consumed during the hospital stay across isavuconazole routes of administration (oral, parenteral, and mixed administration) were identified, quantified, valued and compared via a cost analysis that adopted the healthcare payer perspective. RESULTS: In total, 101 cases with isavuconazole treatment were identified (oral: n = 22, 21.8%; parenteral: n = 59, 58.4%; mixed: n = 20, 19.8%). Median total LOS was greater in the mixed group (46.5 days; p = .009). Median ICU LOS and ventilation duration were both longest in the parenteral-only group (16 days, p = .008; 224 h, p = .003). Invasive aspergillosis was the most frequent isavuconazole indication (n = 86, 85.2%). Average hospital costs were highest in the mixed group (€ 101,226). The median overall costs of cases treated with isavuconazole was € 52,050. CONCLUSIONS: Treating IFD is resource intensive, often requires intensive care and implies high rates of in-hospital mortality. Our study emphasises the high hospital treatment costs and thus the need for reimbursement systems to enable live-saving costly treatments.

Efficacy and Tolerability of Twice-Daily Dosing Schedule of Deferasirox in Transfusion-Dependent Paediatric Beta-Thalassaemia Patients: A Randomized Controlled Study.

Background: Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. Methods: This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. Results: Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. Conclusion: This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.

Synthesis and biological evaluation of 1,2,3-triazole hybrids of 4-methoxy ethyl cinnamate isolated from Hedychium spicatum (Sm) rhizomes: identification of antiproliferative lead actives against prostate cancer.

A series of 1, 2, 3- triazole hybrids (9a-9n) were synthesised from major phenolic constituent, 4-methoxy ethyl cinnamate (5) isolated from rhizomes of Hedychium spicatum (Sm), a traditional medicinal plant used in variety of disease conditions. All the synthesised analogues were tested for their in vitro antiproliferative potential against HCT 116 (colon cancer), A549 (lung cancer), DU-145 (prostate cancer), Hep G2 (hepatoma) and HEK-293 (normal) cell lines. Among the compounds tested, compounds 9i and 9k potently arrested proliferation of DU-145 (prostate cancer) cell line. Compound 9i displayed 20 times better antiproliferative potential than parent compound and almost identical inhibitory activity to that of the standard drug, doxorubicin. The flow cytometric analysis revealed that 9i arrested cells in G2/M phase of cell cycle and induced apoptosis. Overall, the hybrid derivative 9i was found to be a potential antiproliferative lead against prostate cancer.

Triazole based novel molecules as potential therapeutic agents: Synthesis, characterization, biological evaluation, in-silico ADME profiling and molecular docking studies.

In this study, eight new compounds (7a-h) based on triazole compounds containing ester groups were synthesized with high yields. The structures of the synthesized compounds (7a-h) were elucidated by various spectroscopic methods (element analysis, FT-IR, 1H-(13C) NMR). Antioxidant, anticancer, and α-amylase enzyme inhibition activities of synthesized new triazole derivatives were carried out, and the effects of different groups on the activity were investigated. When the determined antioxidant properties of the compounds were examined, all synthesized compounds showed a moderate radical scavenging effect against radicals depending on the concentration (6.25-200 g/mL). All compounds except the three derivatives were found to have higher IC50 values than the standard drug acarbose (IC50: 891 µg/mL) according to the α-amylase enzyme inhibition results. Compound 7g (IC50: 50 g/mL) was discovered to have nearly eighteen (18) times the activity of the conventional medication acarbose (IC50: 891 µg/mL). Compounds synthesized for anticancer activity studies were screened against the Hela cell line, and the results were compared with standard cis-platinum (IC50: 16.30 µg/mL). Compound 7g (IC50: 19.78 µg/mL) was found to have almost the same activity as cis-platinum. Using Qikprop, the compounds were thoroughly tested for ADME qualities, and none violated any drug similarity standards. According to ADME data, whole physicochemical drug-likeness parameters of molecules remained within defined ranges as stipulated in the Lipinski rules (RO5) and revealed a high bioavailability profile. The molecular docking results with 2QV4 and 4GQR alpha-amylase enzymes demonstrated that all molecules have a high affinity, indicating polar and apolar interaction with critical amino acids in the α-amylase binding pocket.

Design, synthesis and antifungal activities of novel triazole derivatives with selenium-containing hydrophobic side chains.

In this work, a series of novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). All compounds were characterized by HRMS, 1H NMR and 13C NMR. Then, their antifungal activities against eight human pathogenic fungi were evaluated in vitro by testing the minimal inhibitory concentrations. The results showed that nearly all tested compounds were found to be more potent against all tested fungal strains than control drug fluconazole. Further mechanism study demonstrated that the target compounds had fungal CYP51 inhibitory activity. Meanwhile, representative compounds revealed low cytotoxic effects toward mammalian cell lines. In addition, the docking results showed that the target compounds bound to Candida albicans CYP51 in a better pattern than fluconazole, especially in the narrow hydrophobic cleft. Overall, the novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains can be further developed for the potential treatment of invasive fungal infections.