Synthesis, insecticidal Activity, and molecular docking analysis of some benzo[h]quinoline derivatives against Culex pipiens L. Larvae.

Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.

Synthesis and in silico studies of certain benzo[f]quinoline-based heterocycles as antitumor agents.

A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,ß-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were - 6.6320 kcal/mol (with RMSD of 0.9477 Å) and - 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties.

ß-Enaminonitrile in the synthesis of tetrahydrobenzo[b]thiophene candidates with DFT simulation, in vitro antiproliferative assessment, molecular docking, and modeling pharmacokinetics.

Among sulfur-including heterocycles, the benzothiophene skeleton is one of the worthy structure fragments that exhibit structural similarities with active substrates to develop various potent lead molecules in drug design. Thus, some tetrahydrobenzo[b]thiophene candidates were prepared from the ß-enaminonitrile scaffold via reactions with diverse carbon-centered electrophilic reagents and supported with DFT studies. The in vitro antiproliferative effect was screened against MCF7 and HePG2 cancer cell lines, and the results displayed the highest potency of imide 5, Schiff base 11, and phthalimido 12 candidates. A molecular docking study was operated to explore the probable binding modes of interaction, and the results revealed the good binding affinity of compounds 5, 11, and 12 toward the tubulin protein (PDB ID 5NM5) with respect to paclitaxel (a tubulin inhibitor) and co-crystallized ligand (GTP). Besides, modeling pharmacokinetics analyses displayed their desirable drug-likeness and bioavailability properties.

Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies.

Some hexahydroquinoline candidates were prepared by reacting 2-amino-3-cyano-1-cyclohexylhexahydroquinoline with oxalyl chloride and triethyl orthoformate. The computational chemical approach agreed with the product-testing results. The produced substances were examined in vitro for their antiproliferative activity against liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT116) cell lines. The highest potency against the four cell lines was exhibited by hydrazide, thiosemicarbazide, and thiazolidinone derivatives. The best docking score was presented by thiosemicarbazide and thiazolidinone derivatives as they showed the highest binding to the Mcl-1 enzyme with binding energies of -8.97 and -8.90 kcal mol-1, respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of -8.74 kcal mol-1. Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.

Synthesis and antimicrobial activity of thiophene-based heterocycles derived from thiophene-2-carbohydrazide.

Aim: Thiophene-based heterocycles were synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Candida albicans strains. Methods: Antimicrobial activity was determined using the broth microdilution method. Results: Spiro-indoline-oxadiazole 17 displayed the highest activity against C. difficile while having no effects against other bacterial strains. Compounds 8 and 16 displayed strong effects against TolC, an outer membrane protein, mutant E. coli. The results of computational chemical study and outcomes of experiments were in good agreement. A molecular docking study was conducted using a molecular operating environment to simulate the binding energies of the potent compounds with D-alanine ligase protein. Conclusion: This study suggests that spiro-indoline-oxadiazole 17 could be a good anticlostridial agent.

A series of thiophene-based heterocycles was synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Candida albicans strains. Notablly, a spiro­indoline­oxadiazole derivative displayed the highest activity against C. difficile with minimum inhibitory concentration values of 2 to 4 µg/ml. Interestingly, this compound exhibited no effects against other tested bacterial strains. For C. difficile, drugs that can inhibit it without affecting other Gram-positive or Gram-negative bacteria (not affecting the normal microbiota) are needed. This compound could be a good anticlostridial agent.

Synthesis, computational chemical study, antiproliferative activity screening, and molecular docking of some thiophene-based oxadiazole, triazole, and thiazolidinone derivatives.

Thiophene-2-carbohydrazide was used in this study to produce some thiophene-containing oxadiazole, triazole, and thiazolidinone derivatives through reactions with various carbon-centered electrophiles. Besides, the hydrazone obtained was allowed to react with mercaptoacetic acid and acetic anhydride to construct thiazolidinone and oxadiazole derivatives. The results of computational chemical study and outcomes of the experiments were in good agreement. The in vitro antiproliferative activity of the produced compounds was examined against two human cell lines namely, breast adenocarcinoma (MCF7) and colon cancer (HCT116) cell lines using doxorubicin as a reference anticancer agent. The produced hydrazones and spiro-indolin-oxadiazole derivatives were the most potent against the two cancer cell lines. The molecular docking was conducted to demonstrate the binding energies of produced substances toward human carbonic anhydrase IX (CA IX) protein. The binding energies of these ligands were near to that of the co-crystallized ligand (9FK). Compound 11b exhibits a binding energy of -5.5817 kcal mol-1, indicating tight binding to some key nucleobases and amino acids of CA IX protein, while compound 11a displays a higher binding energy compared to the reference ligand (9FK). This suggests that compounds 11b and 11a display a notably strong binding affinity towards the human carbonic anhydrase IX (CA IX) protein. ADME profiles of the potent compounds including physicochemical characteristics, lipophilicity, and drug-likeness were predicted.

Religious, Cultural, and Sex Influences on Advance Care Directives in Patients Admitted to a Tertiary Care Center in Kenya.

INTRODUCTION: Advance care directives (AD) are instructions from patients regarding the care they would prefer if they could not make medical decisions in the future. It is widely recognized that racial and ethnic as well as sex differences, particularly in the West, can influence AD. However, to the best of our knowledge, there is limited understanding of how these factors impact AD in sub-Saharan Africa. METHODS: This prospective cross-sectional study was conducted at the Aga Khan University Hospital, Nairobi. We enrolled patients above the age of 18 years who were admitted to the general medical wards. The data were collected using a structured questionnaire that consisted of questions based on demographics and AD. Descriptive statistics were used to summarize the data, including frequencies and percentages, as well as medians and interquartile ranges. RESULTS: The study involved 286 participants, with a median age of 44.0 years (IQR: 37.0 - 52.0). Roughly half of the participants were male (51.7%), and the majority identified themselves as Christians (77.3%) and of African ethnicity (78.3%). Upon further analysis, it was discovered that only 35.3% had an awareness of AD. Notably, individuals from the Hindu religion and Asian ethnicity demonstrated significantly higher knowledge of AD. Furthermore, more males reported having a living will and believed that AD are crucial for patients who could not make independent medical decisions compared to females. CONCLUSION: This study indicated a lower awareness and knowledge of AD among the participants. Hindus and Asians exhibited higher levels of awareness regarding AD. Considering the diverse religious and cultural backgrounds in our setting, there is a pressing need for strategies to increase awareness surrounding AD.

Adsorption characteristics of nickel (II) from aqueous solutions by Zeolite Scony Mobile-5 (ZSM-5) incorporated in sodium alginate beads.

Nickel, a prevalent metal in the ecosystem, is released into the environment through various anthropogenic activities, leading to adverse effects. This research explored utilizing zeolite scony mobile-5 (ZSM-5) nanoparticles encapsulated in sodium alginate (SA) for nickel (II) removal from aqueous solutions. The adsorption characteristics of SA/ZSM-5 were examined concerning contact duration, initial metal ion concentration, pH level, temperature, and sorbent dosage. The findings revealed that a rising pH reduced Ni (II) uptake by the sorbent while increasing the Ni (II) concentration from 25 to 100 mg L-1 led to a decrease in removal percentage from 91 to 80% under optimal conditions. Furthermore, as sorbent dosage increased from 4 to 16 g L-1, uptake capacity declined from 9.972 to 1.55 mg g-1. Concurrently, SA/ZSM-5 beads' Ni (II) sorption capacity decreased from 96.12 to 59.14% with a temperature increase ranging from 25 to 55 °C. The Ni (II) sorption data on SA/ZSM-5 beads are aptly represented by Langmuir and Freundlich equilibrium isotherm models. Moreover, a second-order kinetic model characterizes the adsorption kinetics of Ni (II) on the SA/ZSM-5 beads. A negative free energy change (ΔG°) demonstrates that the process is both viable and spontaneous. The negative enthalpy values indicate an exothermic nature at the solid-liquid interface while negative entropy values suggest a decrease in randomness. In conclusion, this novel adsorbent exhibits promise for removing nickel from aqueous solutions and could potentially be employed in small-scale industries under similar conditions.

Correction: Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment.

[This corrects the article DOI: 10.1371/journal.pone.0196254.].

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives.

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with - 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

Stop-bang questionnaire for screening obstructive sleep apnea syndrome among hypertensive patients in Kenya.

INTRODUCTION: Obstructive sleep apnea (OSA) is a type of breathing problem during sleep caused by the blockage of the upper airway, which can cause cessation of airflow. There is limited research on the prevalence of OSA in hypertensive patients in sub-Saharan Africa (SSA). The study aimed to describe the prevalence and clinical characteristics of OSA among hypertensive patients at a tertiary hospital in Nairobi, Kenya. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital in Nairobi, Kenya. Two hundred and fifty-one hypertensive patients were screened for OSA risk using the STOP-Bang questionnaire (SBQ). Patients with a SBQ score of ≥ 4 were categorized as high risk for OSA. Descriptive statistics were employed to describe both categorical and continuous variables and binary logistic regression to assess factors associated with the high risk of OSA. RESULTS: The study reported that 78.5% of the participants had high-risk OSA. The median age and body mass index (BMI) were 57.0 years (IQR: 50.0-64.0) and 28.3 kg/m2, respectively. Age, neck circumference, gender, and BMI were significantly higher in the high-risk OSA group as compared to the low-risk group. CONCLUSION: The study highlights the importance of screening hypertensive patients for OSA using the SBQ in clinical settings, particularly in low-and middle-income countries (LMICs). Healthcare providers can use patient characteristics such as age, gender, neck circumference, and BMI to identify those at greater risk of developing OSA. Further research could focus on developing effective OSA prevention and treatment interventions in hypertensive patients.

An electronic health record system implementation in a resource limited country-lessons learned.

Electronic health records have revolutionized the medical world by improving medical care, refining provider documentation, standardizing care, and minimizing sentinel events. Successful implementation of electronic health records remains a daunting task and requires careful strategic planning and buy-in from key stakeholders. Much has been published in resource-rich settings and high-income countries about implementations of electronic health records. However, little is known about the experience in resource-limited settings where challenges remain unique and distinct from other parts of the world. Our intention is to share lessons learned during implementation of a web-based electronic health record at a tertiary care center in Kenya.

Photosensitization of TiO2 microspheres by novel Quinazoline-derivative as visible-light-harvesting antenna for enhanced Rhodamine B photodegradation.

Water pollution is one of the global threats severely affecting our planet and human health. Organic textile dyes are one of the common organic water pollutants that are presentient to degradation by traditional physical methods. Semiconductor-assisted photocatalysis is considered a green, efficient, and sustainable technology for wastewater treatment. To maximize the efficient utilization of solar radiation, it is of pivotal significance to explore novel organic molecules to be employed as efficient dye sensitizers for wide-bandgap semiconductors to extend their performance to the Visible-light region. Hence, in this work, we are proposing the design and synthesis of novel structures of QAD molecule as a dye photosensitizer with extended visible light absorptivity due to the extended π-π/n-π conjugations, to promote the performance of TiO2 nanoparticles to the visible-light region and enhance the charge separation. The physicochemical characterizations confirmed the successful synthesis of QAD, TiO2, and QAD/TiO2 samples with the proposed structures. The anchoring of QAD molecules on the surface of TiO2 caused a substantial improvement in the optical characteristics of TiO2 as well as overcoming its common drawbacks by decreasing its bandgap energy to 2.6 eV, a remarkable reduction of PL intensity indicating reducing the e-h recombination and enhancing the charge separation, and creation of efficient visible light-harvesting antenna in the range of 400-600 nm. Besides, the QAD/TiO2 sample achieved a 3-fold enhancement in the observed rate constant of the photodegradation of Rhodamine B dye compared to the bare TiO2. The parameters affecting the photodegradation process were optimized and the sample displayed outstanding stability after 4 consecutive cycles. Finally, the effect of the scavengers was investigated and [Formula: see text] was proposed to be the most reactive species and the mechanism of the enhancement was suggested based on the electron injection from the QAD's HOMO level to the TiO2's CB. Finally, this work opens the door for various studies for the investigation of the proposed structures or similar structures in various photocatalytic/biomedical applications.

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy.

Bacterial superantigens (SAgs) are effective T-cell stimulatory molecules that lead to massive cytokine production. Superantigens crosslink between MHC class II molecules on the Antigen Presenting Cells (APC) and TCR on T-cells. This enables them to activate up to 20% of resting T cells, whilst conventional antigen presentation results in the activation of 0.001-0.0001% of the T cell population. These biological properties of superantigens make them attractive for use in immunotherapy. Previous studies have established the effectiveness of superantigens as therapeutic agents. This, however, was achieved with severe side effects due to the high lethality of the native toxins. Our study aims to produce superantigen-based peptides with minimum or no lethality for safer cancer treatment. In previous work, we designed and synthesized twenty overlapping SPEA-based peptides and successfully mapped regions in SPEA superantigen, causing a vasodilatory response. We screened 20 overlapping SPEA-based peptides designed and synthesized to cover the whole SPEA molecule for T-cell activation and tumor-killing ability. In addition, we designed and synthesized tumor-targeted superantigen-based peptides by fusion of TGFαL3 either from the N' or C' terminal of selected SPEA-based peptides with an eight-amino acid flexible linker in between. Our study identified parts of SPEA capable of stimulating human T-cells and producing different cytokines. We also demonstrated that the SPEA-based peptide conjugate binds specifically to cancer cells and can kill this cancer. Peptides induce T-cell activation, and tumor killing might pave the way for safer tumor-targeted superantigens (TTS). We proposed the combination of our new superantigen-based peptide conjugates with other immunotherapy techniques for effective and safer cancer treatment.

Discrimination and Abuse Among Healthcare Workers from Patients and their Relatives at a Tertiary Hospital in Kenya.

Discrimination and abuse of healthcare workers (HCWs) by patients and their relatives remains a pressing and prevalent problem in various healthcare settings, negatively affecting professional outcomes. Despite this, little has been reported about discrimination and abuse in many low- and middle-income countries such as Kenya. We conducted a cross-sectional survey study between May - August 2021 among healthcare workers at a hospital in Kenya. Email invitations were sent, and the survey was in English, and the data was collected through and online survey. Discrimination based on gender was reported by 24.9% of all HCWs; 39.9% of doctors, 17.2% of nurses, and 10.9% of allied staff whereas racial discrimination was reported by 28.8% of all HCWs; 49.0% of doctors, 18.9% of nurses, and 8.9% of allied staff. Verbal or emotional abuse was the most common form of abuse and was reported by 56.8% of all HCWs while physical abuse was reported by 4.9% of all HCWs. For those that reported discrimination based on gender, 77.4% reported patient and their family members as the main source, whereas 81.2% of those that reported discrimination based on race reported the main source was from patient and their family members. Despite strict laws against discrimination and abuse, a significant portion of healthcare providers suffer from discrimination and abuse primarily from patients and their family members. In addition to education programs and policies to curb such behavior in the work environment, coping mechanisms should be actively sought to help healthcare providers deal with such actions.

COVID-19 Presenting as a Seizure: A Kenyan Case Report.

The new coronavirus quickly spread throughout the world in late 2019 and became a pandemic in early 2020. The most common symptoms observed are fever, dry cough, loss of taste and smell, and respiratory distress. Other rarer complications can involve the cardiovascular, gastrointestinal, or neurological systems. Of the neurological complications, epileptic seizures are a subject of particular interest due to their relatively unknown and widespread etiologies. It is understood that the entry or production of pro-inflammatory cytokines during a COVID-19 infection can result in neurotransmitter modulation and ion channel dysfunction, leading to neuronal hyperexcitability, presenting as seizures. To the best of our knowledge, we present the first case in sub-Saharan Africa of a COVID-19 positive patient presenting to our institution with a reported seizure followed by confusion. Our case highlights the need to broaden our differential diagnosis to include COVID-19 infections in patients presenting with seizures.

Synthesis, SAR studies, and insecticidal activities of certain N-heterocycles derived from 3-((2-chloroquinolin-3-yl)methylene)-5-phenylfuran-2(3H)-one against Culex pipiens L. larvae.

An acid hydrazide derivative was synthesized and transformed into a variety of valuable N-heterocycles such as pyridazinone, oxadiazole, triazolopyridazinone, and triazole derivatives via reactions with certain carbon electrophiles such as 4-methoxybenzaldehyde, indole-3-carbaldehyde, pentan-2,4-dione, and carbon disulfide. The chemical structures of all prepared compounds were verified via their analytical and spectroscopic data. The insecticidal activity of the N-heterocycles was evaluated against field and lab strains of the third larval instar of Culex pipiens. All tested compounds exhibited higher larvicidal activity against the lab strains compared to the field strains, with dissimilar ratios. The obtained results demonstrate that the high toxicity achieved by oxadiazole followed the order of furanone, pyridazinone and hydrazide, with lower LC50 values of the hydrazone and N-acetylpyridazinone derivatives compared to that of imidacloprid. Interestingly, these compounds are promising agents for insect pest control, especially since they are insoluble in water and can overcome the disadvantages of neonicotinoid applications in pest management programs.

Cerebral Fat Embolism: A Rare East African Conundrum.

Cerebral fat embolism (CFE) is a potentially fatal condition associated with displaced long bone fracture of the lower extremities. CFE, usually seen in young men, has an incidence ranging between 0.9% and 11% in patients with long bone fractures. CFE can present with various neurological symptoms, and a diffusion-weighted magnetic resonance imaging (MRI) (DWI) remains the definitive diagnostic study. Early treatment of the fracture is crucial in the management of CFE. To the best of our knowledge, we are the first to report a case of CFE in East Africa.