Interplay between gain and loss in arrays of nonlinear plasmonic nanoparticles: toward parametric downconversion and amplification.

With the help of a theoretical model and finite-difference time-domain (FDTD) simulations based on the hydrodynamic-Maxwell model, we examine the effect of difference-frequency generation (DFG) in an array of L-shaped metal nanoparticles (MNPs) characterized by intrinsic plasmonic nonlinearity. The outcomes of the calculations reveal the spectral interplay between gain and loss in the vicinity of the fundamental frequency of the localized surface plasmon resonances. Subsequently, we identify different array thicknesses and pumping regimes facilitating parametric amplification and spontaneous parametric downconversion. Our results suggest that the parametric amplification regime becomes feasible on a scale of hundreds of nanometers and spontaneous parametric downconversion on the scale of tens of nanometers, opening up new exciting opportunities for developing building blocks of photonic metasurfaces.

Sertraline versus escitalopram in South Asians with moderate to severe major depressive disorder: (SOUTH-DEP) a double-blind, parallel, randomized controlled trial.

Objective: The study design included the double-blind, parallel, randomized controlled trial. The aim of this randomized controlled trial was to compare the efficacy and safety of sertraline and escitalopram in participants with moderate to severe major depressive disorder (MDD). Methods: The study was conducted in South Asian participants. A total of 744 participants with moderate to severe MDD were randomly assigned to receive either sertraline or escitalopram for 8 weeks. Drug dosages and titration schedules were based on the recommendations of the prescribing information for each product and according to the judgment of the clinicians involved in the study. The primary outcome measures were changes from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression (CGI) scale as well as the frequency of adverse events in both groups. Baseline MADRS scores in the escitalopram and sertraline groups were 28.2±0.47 (mean±SD) and 29.70±0.46 (mean±SD) respectively, and was no variability in the baseline assessments. Changes in MADRS as well as CGI scales at the end of the study were significant only for the sertraline group whereas they remained statistically nonsignificant for the escitalopram group. Results: The results of the study showed that sertraline was more efficacious than escitalopram in reducing depression rating scales such as MADRS and CGI, and that participants subjectively felt better regarding their symptoms in the sertraline group. Sertraline displays enhanced safety or tolerability than other groups of antidepressants, which frequently cause high levels of drowsiness, dizziness, blurred vision, and other undesirable effects. Adverse events were seen in both groups, but delayed ejaculation was the most frequent adverse event seen in both groups. However, a greater number of participants reported having nausea and insomnia in the sertraline group compared to the escitalopram group. Conclusion: Our study clearly highlights that there is a statistically significant difference in efficacy between sertraline and escitalopram at the doses used in our study. Sertraline was able to significantly lower the depression rating scales like MADRS and CGI in participants with moderate to severe MDD. Participants subjectively felt better regarding their symptoms in the sertraline group. The most frequent adverse event in both groups was delayed ejaculation. From an efficacy standpoint, sertraline was more efficacious than escitalopram. The study indicates that the prevalence of depressive disorders in South Asia is comparable to the global estimate, and Bangladesh and India has higher proportions of people with depressive disorders in South Asia. Additionally, females and older adults (75-79 years) have the highest burden of depressive disorders across all countries in the region. This study's limitation included the absence of a placebo arm. An additional limitation of the current study was the lack of an evaluation of inter-rater reliability and the research sample could not have been uniform in terms of the kind of depressive disorders and bipolarity.

Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer's Disease along with Molecular Docking Study.

Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1-21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase.

A Mathematical Model for Simulation of Vasoplegic Shock and Vasopressor Therapy.

OBJECTIVE: To develop a high-fidelity mathematical model intended to replicate the cardiovascular (CV) responses of a critically ill patient to vasoplegic shock-induced hypotension and vasopressor therapy. METHODS: The mathematical model consists of a lumped-parameter CV physiology model with baroreflex modulation feedback and a phenomenological dynamic dose-response model of a vasopressor. The adequacy of the proposed mathematical model was investigated using an experimental dataset acquired from 10 pigs receiving phenylephrine (PHP) therapy after vasoplegic shock induced via sodium nitroprusside (SNP). RESULTS: Upon calibration, the mathematical model could (i) faithfully replicate the effects of PHP on dynamic changes in blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR) (root-mean-squared errors between measured and calibrated mathematical responses: mean arterial BP 2.5+/-1.0 mmHg, CO 0.2+/-0.1 lpm, SVR 2.4+/-1.5 mmHg/lpm; r value: mean arterial BP 0.96+/-0.01, CO 0.65+/-0.45, TPR 0.92+/-0.10) and (ii) predict physiologically plausible behaviors of unmeasured internal CV variables as well as secondary baroreflex modulation effects. CONCLUSION: This mathematical model is perhaps the first of its kind that can comprehensively replicate both primary (i.e., direct) and secondary (i.e., baroreflex modulation) effects of a vasopressor drug on an array of CV variables, rendering it ideally suited to pre-clinical virtual evaluation of the safety and efficacy of closed-loop control algorithms for autonomous vasopressor administration once it is extensively validated. SIGNIFICANCE: This mathematical model architecture incorporating both direct and baroreflex modulation effects may generalize to serve as part of an effective platform for high-fidelity in silico simulation of CV responses to vasopressors during vasoplegic shock.

Development and validation of a multivariable mortality risk prediction model for COPD in primary care.

Risk stratification of chronic obstructive pulmonary disease (COPD) patients is important to enable targeted management. Existing disease severity classification systems, such as GOLD staging, do not take co-morbidities into account despite their high prevalence in COPD patients. We sought to develop and validate a prognostic model to predict 10-year mortality in patients with diagnosed COPD. We constructed a longitudinal cohort of 37,485 COPD patients (149,196 person-years) from a UK-wide primary care database. The risk factors included in the model pertained to demographic and behavioural characteristics, co-morbidities, and COPD severity. The outcome of interest was all-cause mortality. We fitted an extended Cox-regression model to estimate hazard ratios (HR) with 95% confidence intervals (CI), used machine learning-based data modelling approaches including k-fold cross-validation to validate the prognostic model, and assessed model fitting and discrimination. The inter-quartile ranges of the three metrics on the validation set suggested good performance: 0.90-1.06 for model fit, 0.80-0.83 for Harrel's c-index, and 0.40-0.46 for Royston and Saurebrei's [Formula: see text] with a strong overlap of these metrics on the training dataset. According to the validated prognostic model, the two most important risk factors of mortality were heart failure (HR 1.92; 95% CI 1.87-1.96) and current smoking (HR 1.68; 95% CI 1.66-1.71). We have developed and validated a national, population-based prognostic model to predict 10-year mortality of patients diagnosed with COPD. This model could be used to detect high-risk patients and modify risk factors such as optimising heart failure management and offering effective smoking cessation interventions.

N-([1,1'-biaryl]-4-yl)-1-naphthamide-based scaffolds synthesis, their cheminformatics analyses, and screening as bacterial biofilm inhibitor.

Naphthamides have pharmacological potential as they express strong activities against microorganisms. The commercially available naphthoyl chloride and 4-bromoaniline were condensed in dry dichloromethane (DCM) in the presence of Et3 N to form N-(4-bromophenyl)-1-naphthamide (86%) (3). Using a Pd(0) catalyzed Suzuki-Miyaura Cross-Coupling reaction of (3) and various boronic acids, a series of N-([1,1'-biaryl]-4-yl)-1-naphthamide derivatives (4a-h) were synthesized in moderate to good yields. The synthesized derivatives were evaluated for cytotoxicity haemolytic assay and biofilm inhibition activity through in silico and in vitro studies. Molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity risk, and other cheminformatics predict synthesized molecules as biologically active moieties, further validated through in vitro studies in which compounds (4c) and (4f) showed significant haemolytic activity whereas (4e) exhibited an efficient biofilm inhibition activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. When forming biofilms, bacteria become resistant to various antimicrobial treatments. Currently, research is focused on the development of agents that inhibit biofilm formation, thus the present work is valuable for preventing future drug resistance.

Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.

BACKGROUND: The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear. METHODS: We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting. RESULTS: From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region). CONCLUSIONS: There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.

Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women: 17-Year National Cohort Study.

BACKGROUND: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. OBJECTIVE: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. RESULTS: At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. CONCLUSION: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.

Endoscopic resection reduces morbidity when compared to surgery in veterans with large and complex colorectal polyps.

INTRODUCTION: Data supporting endoscopic resection (ER) over surgical resection (SR) for large and complex polyps come from high-volume centers. The aim of this study was to determine whether these favorable outcomes can be replicated among endoscopists at tertiary Veterans Affairs Medical Centers (VAMCs) who perform 25 to 30 ER cases a year. METHODS: Patients with adenomatous polyps or intra-mucosal cancers ≥ 2 cm in size who underwent ER or SR were identified from prospectively maintained databases at the 2 tertiary VAMCs in Veterans Integrated Service Network 6 (VISN6). The primary outcome was the rate of serious complications in the ER and SR groups. RESULTS: 310 ER and 81 SR patients met the inclusion criteria. ER was successful in 97% of all polyps, and 93% of polyps ≥ 4 cm. The rate of serious complications was significantly lower with ER compared to SR (0.6% vs. 22%, p = 0.00001). These findings persisted even after limiting the analysis to polyps ≥ 4 cm and after propensity score matching. If all ER patients had instead undergone laparoscopic surgery, the estimated risk of a serious complication was still higher than ER for all patients (8% vs. 0.6%, p < 0.0001) but not significantly higher for polyps ≥ 4 cm (8% vs 2%, p = 0.17). CONCLUSIONS: This study documents high success rates for ER in veterans with colorectal polyps ≥ 2 cm and ≥ 4 cm. When compared to a historical cohort of surgical patients, a strategy of attempting ER first reduced morbidity. A randomized trial is warranted to compare ER to laparoscopic surgery for polyps ≥ 4 cm.

Hormone replacement therapy and asthma onset in menopausal women: National cohort study.

BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma. OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women. METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs. RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset. CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

BACKGROUND: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. RESULTS: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. CONCLUSIONS: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. PROTOCOL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies (EUPAS22967).

Sustainable Management of Organic Wastes in Sharjah, UAE through Co-Composting.

Daily human activities and vast green areas produce substantial amounts of organic wastes that end up in landfills with minimal treatment. In addition to the problems associated with landfills, disposal through this method is unsustainable in the long run and does not allow recovering materials from the waste. This paper focuses on the co-composting of different organic wastes produced in The Emirate of Sharjah, United Arab Emirates (UAE), to optimize mixing proportions of three different kinds of wastes-sewage sludge (SS), green waste (GW), and food waste (FW). All three organic wastes were analyzed to determine their chemical composition and the mixing proportions. Ten different mixing proportions as a function of carbon:nitrogen (C:N ratios) were determined and mixed in a NatureMill composter. Compost samples were tested for pH, salinity, conductivity, moisture content, organic matter, organic carbon, phosphorus, total nitrogen, and final C:N ratio after 6 weeks. Results indicate that a period of 5-6 weeks is sufficient for the compost to stabilize. The varying mixing proportions produced a good-quality compost (C:N up to 20:1) with high nutrient content. The study reaffirms that co-composting can be a potential sustainable organic waste management option for the United Arab Emirates.

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study.

BACKGROUND: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS: At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS: Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.

Machine learning driven non-invasive approach of water content estimation in living plant leaves using terahertz waves.

BACKGROUND: The demand for effective use of water resources has increased because of ongoing global climate transformations in the agriculture science sector. Cost-effective and timely distributions of the appropriate amount of water are vital not only to maintain a healthy status of plants leaves but to drive the productivity of the crops and achieve economic benefits. In this regard, employing a terahertz (THz) technology can be more reliable and progressive technique due to its distinctive features. This paper presents a novel, and non-invasive machine learning (ML) driven approach using terahertz waves with a swissto12 material characterization kit (MCK) in the frequency range of 0.75 to 1.1 THz in real-life digital agriculture interventions, aiming to develop a feasible and viable technique for the precise estimation of water content (WC) in plants leaves for 4 days. For this purpose, using measurements observations data, multi-domain features are extracted from frequency, time, time-frequency domains to incorporate three different machine learning algorithms such as support vector machine (SVM), K-nearest neighbour (KNN) and decision-tree (D-Tree). RESULTS: The results demonstrated SVM outperformed other classifiers using tenfold and leave-one-observations-out cross-validation for different days classification with an overall accuracy of 98.8%, 97.15%, and 96.82% for Coffee, pea shoot, and baby spinach leaves respectively. In addition, using SFS technique, coffee leaf showed a significant improvement of 15%, 11.9%, 6.5% in computational time for SVM, KNN and D-tree. For pea-shoot, 21.28%, 10.01%, and 8.53% of improvement was noticed in operating time for SVM, KNN and D-Tree classifiers, respectively. Lastly, baby spinach leaf exhibited a further improvement of 21.28% in SVM, 10.01% in KNN, and 8.53% in D-tree in overall operating time for classifiers. These improvements in classifiers produced significant advancements in classification accuracy, indicating a more precise quantification of WC in leaves. CONCLUSION: Thus, the proposed method incorporating ML using terahertz waves can be beneficial for precise estimation of WC in leaves and can provide prolific recommendations and insights for growers to take proactive actions in relations to plants health monitoring.

Bi-heterocyclic benzamides as alkaline phosphatase inhibitors: Mechanistic comprehensions through kinetics and computational approaches.

Novel bi-heterocyclic benzamides were synthesized by sequentially converting 4-(1H-indol-3-yl)butanoic acid (1) into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3), and a nucleophilic 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4). In a parallel series of reactions, various electrophiles were synthesized by reacting substituted anilines (5a-k) with 4-(chloromethyl)benzoylchloride (6) to afford 4-(chloromethyl)-N-(substituted-phenyl)benzamides (7a-k). Finally, the nucleophilic substitution reaction of 4 was carried out with newly synthesized electrophiles, 7a-k, to acquire the targeted bi-heterocyclic benzamides, 8a-k. The structural confirmation of all the synthesized compounds was done by IR, 1 H NMR, 13 C NMR, EI-MS, and CHN analysis data. The inhibitory effects of these bi-heterocyclic benzamides (8a-k) were evaluated against alkaline phosphatase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 8b inhibited alkaline phosphatase non-competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 1.15 µM. The computational study was in full agreement with the experimental records and these ligands exhibited good binding energy values. These molecules also exhibited mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds to render normal calcification of bones and teeth.

2-Mercaptobenzimidazole Schiff Bases: Design, Synthesis, Antimicrobial Studies and Anticancer Activity on HCT-116 Cell Line.

BACKGROUND: Increased rate of mortality due to the development of resistance to currently available antimicrobial and anticancer agents initiated the need to develop new chemical entities for the treatment of microbial infections and cancer. OBJECTIVE: The present study was aimed to synthesize and evaluate antimicrobial and anticancer activities of Schiff bases of 2-mercaptobenzimidazole. METHODS: The Schiff bases of 2-mercaptobenzimidazole were synthesized from 4-(2-(1H-benzo[d]- imidazol-2-ylthio)acetamido)benzohydrazide. The synthesized compounds were evaluated for antimicrobial and anticancer activities by tube dilution method and Sulforhodamine-B (SRB) assay, respectively. RESULTS: Compounds 8 (MICpa, an = 2.41, 1.20 µM/ml), 10 (MICse, sa = 2.50 µM/ml), 20 (MICec = 2.34 µM/ml) and 25 (MICca = 1.46 µM/ml) showed significant antimicrobial activity against tested bacterial and fungal strains and compounds 20 (IC50 = 8 µg/ml) and 23 (IC50 = 7 µg/ml) exhibited significant anticancer activity. CONCLUSION: In general, the synthesized derivatives exhibited moderate antimicrobial and anticancer activities. Compounds 8 and 25 having high antifungal potential among the synthesized compounds may be taken as lead molecules for the development of novel antifungal agents.