Commonalities and differences in injured patient experiences of accessing and receiving quality injury care: a qualitative study in three sub-Saharan African countries.

OBJECTIVES: To understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries. DESIGN: A qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed. SETTING: Urban and rural settings in Ghana, South Africa and Rwanda. PARTICIPANTS: 59 patients with musculoskeletal injuries. RESULTS: We found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency. CONCLUSION: There are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.

Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights.

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

[Box: see text].

Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Modified Tilt-integral active disturbance rejection controller with inertia emulated direct current link for frequency control of marine microgrid.

The increasing integration of intermittent renewable sources (RSs) poses a dynamic frequency stability challenge for modern marine vessel microgrids. To address this issue, this paper proposes a novel control approach, specifically targeting frequency and tie-line power stabilization in a diverse source marine microgrid (MµG) with two intertied areas featuring renewable (wind-wave) sources. The suggested approach introduces a modified tilt-integral active disturbance rejection (TI-ADRC) controller designed to ensure effective damping of power frequency oscillations. As the control scheme depends on the optimal setting of the proposed controller, a recently developed marine predator technique (MPT) has been adopted. The performance of the proposed controller is compared with other recent controllers viz. PID, tilt-integral derivative (TID), two-degree-of-freedom (2DOF)-PID, fuzzy-PI, and ADRC to validate its superiority. To further enhance the system dynamics, a precise modeling of inertia emulated direct current (IEPDC) tie link is incorporated in microgrid system. The impact assessments, considering time delays with pre/post IEPDC link, demonstrate a substantial 57.79% and 81.53% reduction in peak frequency overshoot compared to DC link (conventional model) and AC link, respectively. The analysis of the eigen plot confirms the stability of the control system. Sensitivity assessments of the controller against ± 30% parametric variations and load fluctuations are conducted, affirming its robustness. Finally, the result from OPAL-RT confirm the practicality of the proposed method. It is asserted that the suggested controller is reliable and functions well in n the presence of diverse disruptions and parametric variations.

Designing and Synthesis of Novel Fexofenadine-Derived Hydrazone-Schiff bases as Potential Urease Inhibitors: In-Vitro, Molecular Docking and DFT Investigations.

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50=10.19±0.16 µM), 11 (IC50=15.05±1.11 µM), 10 (IC50=17.01±1.23 µM), 9 (IC50=17.22±0.81 µM), 13 (IC50=19.31±0.18 µM), and 14 (IC50=19.62±0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50=21.14±0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

A qualitative examination of factors influencing pregnancy-related anxiety in Northern Ghana.

INTRODUCTION: Despite high prevalence of anxiety among pregnant women in low- and -middle-income countries, research on context-specific conceptualisation, measurement, and predictors of pregnancy-related anxiety (PrA) is limited in these contexts. We explored local conceptualisations of factors influencing PrA in the Northern Region of Ghana. METHODS: We conducted 15 focus group discussions with antenatal care seekers in the Mion District, Savelugu Municipality, and Tamale Metropolis of the Northern Region, in July and August 2021. Multistage stratified purposive sampling was used to select respondents (n = 108). The data were audio-recorded and transcribed, and then we conducted a thematic analysis of the data. RESULTS: At the individual level, fear of anaemia; pre-existing health conditions; challenges with daily activities; and physical, emotional, and sexual abuses from spouses contributed to PrA. Health system failures resulting in unexpected out-of-pocket payments, negative health worker attitudes, diagnostic errors, constraints on birth preparation and birth process, and potential adverse birth outcomes were understood as driving PrA. Socio-cultural factors influencing PrA comprised beliefs and practices around baby naming/outdooring ceremonies, fear of spiritual attacks, social construction of gender roles, and contextual factors such as transportation challenges. CONCLUSION: Pregnant women in the region understood, experienced, and could identify perceived predictors of PrA. To address PrA, we recommend that mental health services should be integrated into the basic package of antenatal care and rural health services should be improved. Perceived predictors of PrA identified here could be included in the design of a context-specific PrA measure for use in the region.

Synthesis of hydrazone-based polyhydroquinoline derivatives - antibacterial activities, α-glucosidase inhibitory capability, and DFT study.

In recent years, polyhydroquinolines have gained much attention due to their widespread applications in medicine, agriculture, industry, etc. Here, we synthesized a series of novel hydrazone-based polyhydroquinoline derivatives via multi-step reactions. These molecules were characterized by modern spectroscopic techniques (1H-NMR, 13C NMR, and LC-HRMS) and their antibacterial and in vitro α-glucosidase inhibitory activities were assessed. Compound 8 was found to be the most active inhibitor against Listeria monocytogenes NCTC 5348, Bacillus subtilis IM 622, Brevibacillus brevis, and Bacillus subtilis ATCC 6337 with a zone of inhibition of 15.3 ± 0.01, 13.2 ± 0.2, 13.1 ± 0.1, and 12.6 ± 0.3 mm, respectively. Likewise, compound 8 also exhibited the most potent inhibitory potential for α-glucosidase (IC50 = 5.31 ± 0.25 µM) in vitro, followed by compounds 10 (IC50 = 6.70 ± 0.38 µM), and 12 (IC50 = 6.51 ± 0.37 µM). Furthermore, molecular docking and DFT analysis of these compounds showed good agreement with experimental work and the nonlinear optical properties calculated here indicate that these compounds are good candidates for nonlinear optics.

Novel hydrazone schiff's base derivatives of polyhydroquinoline: synthesis, in vitro prolyl oligopeptidase inhibitory activity and their Molecular docking study.

This research work reports the synthesis of new derivatives of the hydrazone Schiff bases (1-17) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,1H- and 13C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal. Three derivatives 3, 15 and 14 showed excellent inhibition with IC50 values 3.21 ± 0.15 to 5.67 ± 0.18 µM, while the remaining 12 compounds showed significant activity. Docking studies indicated a good correlation with the biochemical potency of compounds estimated in the in-vitro test and showed the potency of compounds 3, 15 and 14. The MD simulation results confirmed the stability of the most potent inhibitors 3, 15 and 14 at 250 ns using the parameters RMSD, RMSF, Rg and number of hydrogen bonds. The RMSD values indicate the stability of the protein backbone in complex with the inhibitors over the simulation time. The RMSF values of the binding site residues indicate that the potent inhibitors contributed to stabilizing these regions of the protein, through formed stable interactions with the protein. The Rg. analysis assesses the overall size and compactness of the complexes. The maintenance of stable hydrogen bonds suggests the existence of favorable binding interactions. SASA analysis suggests that they maintained stable conformations without large-scale exposure to the solvent. These results indicate that the ligand-protein interactions are stable and could be exploited to design new drugs for disease treatment.Communicated by Ramaswamy H. Sarma.

Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 µM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Governance for injury care systems in Ghana, South Africa and Rwanda: development and pilot testing of an assessment tool.

OBJECTIVES: This study aims to evaluate health systems governance for injury care in three sub-Saharan countries from policymakers' and injury care providers' perspectives. SETTING: Ghana, Rwanda and South Africa. DESIGN: Based on Siddiqi et al's framework for governance, we developed an online assessment tool for health system governance for injury with 37 questions covering health policy and implementation under 10 overarching principles of strategic vision, participation and consensus orientation, rule of law, transparency, responsiveness of institutions, equity, effectiveness or efficiency, accountability, ethics and intelligence and information. A literature review was also done to support the scoring. We derived scores using two methods-investigator scores and respondent scores. PARTICIPANTS: The tool was sent out to purposively selected stakeholders, including policymakers and injury care providers in Ghana, Rwanda and South Africa. Data were collected between October 2020 and February 2021. PRIMARY AND SECONDARY OUTCOMES: Investigator-weighted and respondent percentage scores for health system governance for injury care. This was calculated for each country in total and per principle. RESULTS: Rwanda had the highest overall investigator-weighted percentage score (70%), followed by South Africa (59%). Ghana had the lowest overall investigator score (48%). The overall results were similar for the respondent scores. Some areas, such as participation and consensus, scored high in all three countries, while other areas, such as transparency, scored very low. CONCLUSION: In this multicountry governance survey, we provide insight into and evaluation of health system governance for trauma in three low- and middle-income countries (LMICs) in sub-Saharan Africa. It highlights areas of improvement that need to be prioritised, such as transparency, to meet the high burden of trauma and injuries in LMICs.

Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking.

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.

Barriers to equitable access to quality trauma care in Rwanda: a qualitative study.

OBJECTIVES: Using the 'Four Delay' framework, our study aimed to identify and explore barriers to accessing quality injury care from the injured patients', caregivers' and community leaders' perspectives. DESIGN: A qualitative study assessing barriers to trauma care comprising 20 in-depth semistructured interviews and 4 focus group discussions was conducted. The data were analysed thematically. SETTING: This qualitative study was conducted in Rwanda's rural Burera District, located in the Northern Province, and in Kigali City, the country's urban capital, to capture both the rural and urban population's experiences of being injured. PARTICIPANTS: Purposively selected participants were individuals from urban and rural communities who had accessed injury care in the previous 6 months or cared for the injured people, and community leaders. Fifty-one participants, 13 females and 38 males ranging from 21 to 68 years of age participated in interviews and focus group discussions. Thirty-six (71%) were former trauma patients with a wide range of injuries including fractured long bones (9, 45%), other fractures, head injury, polytrauma (3, 15% each), abdominal trauma (1, 5%), and lacerations (1, 5%), while the rest were caregivers and community leaders. RESULTS: Multiple barriers were identified cutting across all levels of the 'Four Delays' framework, including barriers to seeking, reaching, receiving and remaining in care. Key barriers mentioned by participants in both interviews and focus group discussions were: lack of community health insurance, limited access to ambulances, insufficient number of trauma care specialists and a high volume of trauma patients. The rigid referral process and lack of decentralised rehabilitation services were also identified as significant barriers to accessing quality care for injured patients. CONCLUSIONS: Future interventions to improve access to injury care in Rwanda must be informed by the identified barriers along the spectrum of care, from the point of injury to receipt of care and rehabilitation.

New supramolecules of bis(acylhydrazones)-linked bisphenol sulfide for Alzheimer's: targeting cholinesterases by in vitro and in silico approaches.

In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.

Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes.

Polyhydroquinoline derivatives (1-15) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds (1-15) were deduced through different spectroscopic techniques such as 1H NMR, 13C NMR, and HR-ESI-MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC50 = 0.56 ± 0.01 µM), 10 (IC50 = 0.94 ± 0.01 µM), 4 (IC50 = 1.47 ± 0.01 µM), 2 (IC50 = 2.20 ± 0.03 µM), 6 (IC50 = 2.20 ± 0.03 µM), 12 (IC50 = 2.22 ± 0.07 µM), 7 (IC50 = 2.76 ± 0.04 µM), 9 (IC50 = 2.78 ± 0.03 µM), and 3 (IC50 = 2.88 ± 0.05 µM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (8, 5, 14, 15, and 13) showed significant α-glucosidase inhibitory potential with IC50 values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 µM, respectively. Among the synthesized series, two compounds, i.e., 11 and 10, showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug "acarbose" (IC50 = 873.34 ± 1.67 µM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results.

Social Determinants of Seeking and Reaching Injury Care in South Africa: A Community-Based Qualitative Study.

Background: Timely access to quality injury care saves lives and prevents disabilities. The impact of social determinants of health on the high injury prevalence in South Africa is well documented, however, evidence of their role in accessing injury care is lacking. This study explored the social determinants of seeking and reaching injury care in South Africa. Methods: This was a qualitative study involving rural and urban patients, community members, and healthcare providers in Western Cape, South Africa. Data were obtained through semi-structured interviews and focus group discussions using an interview guide informed by the four-delays framework. Inductive and deductive approaches were used for thematic analysis. Results: A total of 20 individual interviews and 5 focus group discussions were conducted. There were 28 males (individual interviews: 13; focus groups: 15) and 22 females (individual interviews: 7; focus groups: 15), and their mean age was 41 (standard deviation ±15) years. Barriers to seeking and reaching injury care cut across five social determinants of health domains: healthcare access and quality; neighbourhood and environment; social and community context; education; and economic stability. The most prominent social determinants of seeking and reaching injury care were related to healthcare access and quality, including perceived poor healthcare quality, poor attitude of healthcare workers, long waiting time, and ambulance delays. However, there was a strong interconnection between these and neighbourhood and environmental determinants such as safety concerns, high crime rates, gangsterism, lack of public transportation, and social and community factors (presence/absence of social support and alcohol use). Barriers related to education and economic stability were less prevalent. Conclusion: We found a substantial role of neighbourhood, social, and community factors in seeking and reaching injury care. Therefore, efforts aimed at improving access to injury care and outcomes must go beyond addressing healthcare factors to include other social determinants and should involve collaborations with multiple sectors, including the community, the police, the transport department, and alcohol regulation agencies.

Synthesis and characterization of biologically active flurbiprofen amide derivatives as selective prostaglandin-endoperoxide synthase II inhibitors: In vivo anti-inflammatory activity and molecular docking.

A novel series of twenty two flurbiprofen amides (1-22) were designed and synthesized in good to excellent yields by reacting flurbiprofen acid with various aromatic/aliphatic primary amines in the presence of 1,1­carbonyldiimidazole (CDI) in basic medium using acetonitrile as solvent. Structures of the synthesized derivatives were elucidated with the help of HR-ESI-MS, 1H-, and 13C NMR spectroscopy and finally screened them for their in-vivo anti-inflammatory potential using carrageenan induced mice paw oedema assay. Among the series, four compounds (8, 14, 15, and 20) displayed excellent activity ranging from 59.0 to 77.7 % decrease, while eight compounds (1, 3, 7, 10, 12, 13, 17, and 18) exhibited good activity in the decrease range of 37.0-50.0 %. Additionally, four compounds (2, 6, 16, and 22) attributed less activity, while the remaining six compounds (4, 5, 9, 11, 19, and 21) were found to be inactive. Furthermore, the In-silico studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of prostaglandin endoperoxide-synthase II enzyme.

Cow bone-derived biochar enhances microbial biomass and alters bacterial community composition and diversity in a smelter contaminated soil.

Bone waste could be utilized as a potential amendment for remediation of smelter-contaminated soils. Nevertheless, the influences of cow bone-derived biochar (CB) on soil microbial biomass and microbial community composition in multi-metal contaminated mining soils are still not clearly documented. Hence, the cow bone was used as feedstock material for biochar preparation and pyrolyzed at two temperatures such as 500 °C (CB500) and 800 °C (CB800), and added to a smelter soil at the dosage of 0 (unamended control), 2.5, 5, and 10% (w/w); then, the soil treatments were cultivated by maize. The CB effect on soil biochemical attributes and response of soil microbial biomass, bacterial communities, and diversity indices were examined after harvesting maize. Addition of CB enhanced total nutrient contents (i.e., total nitrogen up to 26% and total phosphorus P up to 27%) and the nutrients availability (i.e., NH4 up to 50%; NO3 up to 31%; Olsen P up to 48%; extractable K up to 18%; dissolved organic carbon up to 74%) in the treated soil, as compared to the control. The CB500 application revealed higher microbial biomass C (up to 66%), P (up to 41%), and bacterial gene abundance (up to 76%) than the control. However, comparatively a lower microbial biomass nitrogen and diversity indices were observed in the biochar (both with CB500 and CB800) treated soils than in the unamended soils. At the phylum level, the highest dose (10% of CB500 and CB800 resulted in contrasting effects on the Proteobacteria diversity. The CB50010 favored the Pseudomonas abundance (up to 793%), Saccharibacteria (583%), Parcubacteria (138%), Actinobacteria (65%), and Firmicutes (48%) microbial communities, while CB80010 favored the Saccharibacteria (386%), Proteobacteria (12%) and Acidobacteria (11%), as compared to the control. These results imply that CB500 and CB800 have a remarkable impact on microbial biomass and bacterial diversity in smelter contaminated soils. Particularly, CB500 was found to be suitable for enhancing microbial biomass, bacterial growth of specific phylum, and diversity, which can be useful for bioremediation of mining soils.

Biooriented Synthesis of Ibuprofen-Clubbed Novel Bis-Schiff Base Derivatives as Potential Hits for Malignant Glioma: In Vitro Anticancer Activity and In Silico Approach.

This research work is based on the synthesis of bis-Schiff base derivatives of the commercially available ibuprofen drug in outstanding yields through multistep reactions. Structures of the synthesized compounds were confirmed by the help of modern spectroscopic techniques including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1H NMR, and 13C NMR. The synthesized compounds were evaluated for their anticancer activity using a normal human embryonic kidney HEK293 cell and U87-malignant glioma (ATCC-HTB-14) as a cancer cell line. All of the synthesized compounds among the series exhibited excellent to less antiproliferative activity having IC50 values ranging from 5.75 ± 0.43 to 150.45 ± 0.20 µM. Among them, compound 5e (IC50 = 5.75 ± 0.43 µM) was found as the most potent antiprolifarative agent, while 5f, 5b, 5a, 5n, 5r, 5s, 5g, 5q, 5i, and 5j exhibited good activity with IC50 values from 24.17 ± 0.46 to 43.71 ± 0.07 µM. These findings suggest that these cells (HEK293) are less cytotoxic to the activities of compounds and increase the cancer cell death in brain, while the lower cytotoxicity of the potent compounds in noncancerous cells suggests that these derivatives will provide promising treatment for patients suffering from brain cancer. The results of the docking study exposed a promising affinity of the active compounds toward casein kinase-2 enzyme, which shows green signal for cancer treatment.

Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies.

A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a-m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a-m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC50 range: 0.64 ± 0.05 µM to 343.10 ± 1.62 µM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC50: 0.64 ± 0.05 µM) followed by 7d (IC50: 5.34 ± 0.16 µM), 7f (IC50: 6.46 ± 0.30 µM), 7g (IC50: 8.62 ± 0.19 µM), 7c (IC50: 9.84 ± 0.08 µM), 7m (IC50: 11.09 ± 0.79 µM), 7a (IC50: 11.84 ± 0.26 µM), 7e (IC50: 16.38 ± 0.53 µM), 7j (IC50: 18.65 ± 0.74 µM), 7h (IC50: 20.73 ± 0.59 µM), 7b (IC50: 27.26 ± 0.30 µM), 7k (70.28 ± 1.52 µM) and finally 7l (IC50: 343.10 ± 1.62 µM). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings.