Morphology and seed protein profile for a new species of the genus Cleome L. (Cleomaceae) from Pakistan

A new species of the genus Cleome L. from Pakistan is described and illustrated. The new species is described under the name C. karachiensis sp. nov. and compared with two closely related species i.e., Cleome brachycarpa and C. viscosa in terms of morphology, palynology, seed morphology and seed protein profile. A key to the species of genus Cleome L. from Pakistan is also provided

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-27, pub-electronic 2021-10-30Publication status: PublishedAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease

A LATENT GROWTH MODELLING APPROACH TO INVESTIGATING GENDER DIFFERENCES IN THE DEVELOPMENT OF BEHAVIOURAL SELF-REGULATION AND ACADEMIC OUTCOMES FROM KINDERGARTEN TO GRADE 2

A growing body of literature indicates the behavioural aspect of self-regulation, including paying attention, remembering instructions, controlling impulses and directing one’s action, amidst environmental distractions, is a critical component of successful school functioning. Some studies have identified differences between male and female students’ behavioural self-regulation abilities; however, it is unclear whether improvements in this ability are influenced by gender and whether they parallel growth in the development of reading and math abilities. The present study explored gender differences in the development of children’s behavioural self-regulation from kindergarten to Grade 2, using a direct assessment. Longitudinal associations between behavioural self-regulation and early reading and math skills were also examined. A latent growth modelling approach was utilized for the analyses across three waves of data collection. The study participants included 197 children (106 males and 91 females). On average, children were approximately five years old at the start of the study (M =5.39, SD=0.593). The study results revealed gender similarities in behavioural self-regulation growth, positive correlated initial skill levels and rates of growth between behavioural self-regulation and reading, and positive correlated initial skill levels between behavioural self-regulation and math. Implications for future research, as well as educational policies and instructional practices, are discussed.Ph.D

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer’s Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties

Alzheimer’s disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer’s disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4–6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer’s disease (AD)

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H- and 13C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d6 solvent by means of 1H NMR and 13C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E(C=N)(N-N) synperiplanar and E(C=N)(N-N)antiperiplanar at room temperature in DMSO-d6. The ratio of both conformers was also calculated and E(C=N) (N-N) syn-periplanar conformer was established to be in higher percentage in equilibrium with the E(C=N) (N-N)anti-periplanar form

The Impact of Work-Related Stress on Medication Errors in Eastern Region Saudi Arabia

Objective To examine the relationship between overall level and source-specific work-related stressors on medication errors rate. Design A cross-sectional study examined the relationship between overall levels of stress, 25 source-specific work-related stressors and medication error rate based on documented incident reports in Saudi Arabia (SA) hospital, using secondary databases. Setting King Abdulaziz Hospital in Al-Ahsa, Eastern Region, SA. Participants Two hundred and sixty-nine healthcare professionals (HCPs). Main Outcome Measures The odds ratio (OR) and corresponding 95% confidence interval (CI) for HCPs documented incident report medication errors and self-reported sources of Job Stress Survey. Results Multiple logistic regression analysis identified source-specific work-related stress as significantly associated with HCPs who made at least one medication error per month (P \u3c 0.05), including disruption to home life, pressure to meet deadlines, difficulties with colleagues, excessive workload, income over 10 000 riyals and compulsory night/weekend call duties either some or all of the time. Although not statistically significant, HCPs who reported overall stress were two times more likely to make at least one medication error per month than non-stressed HCPs (OR: 1.95, P = 0.081). Conclusion This is the first study to use documented incident reports for medication errors rather than self-report to evaluate the level of stress-related medication errors in SA HCPs. Job demands, such as social stressors (home life disruption, difficulties with colleagues), time pressures, structural determinants (compulsory night/weekend call duties) and higher income, were significantly associated with medication errors whereas overall stress revealed a 2-fold higher trend

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease

(Benzylideneamino)triazole-thione derivatives of flurbiprofen: an efficient microwave-assisted synthesis and in vivo analgesic potential

Triazole is an imperative heterocycle renowned for its broad-spectrum biological significance. In this manuscript, facile microwave-assisted synthesis of a series of 4-(benzylideneamino)-3-(1-(2-fluoro-[1,1′-biphenyl]-4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione 6(a-m) derivatives along with their in vivo analgesic activity is reported. 2-(2-Fluoro-[1,1′-biphenyl]-4-yl)propanoic acid (flurbiprofen) was converted to methyl 2-(2-fluoro-[1,1′-biphenyl]-4-yl)propanoate using microwave irradiation, followed by its hydrazinolysis with hydrazine monohydrate. 2-(2-Fluoro-[1,1′-biphenyl]-4-yl)propanehydrazide thus obtained was converted to 4-amino-3-(1-(2-fluoro-[1,1′-biphenyl]-4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione, followed by its condensation with different aromatic aldehydes to get the title compounds. Structures of all the synthesized compounds were established using different methods (1H NMR and 13C NMR spectroscopies, mass spectrometry, and elemental analysis) and evaluated for their potential as analgesic agents by tail flick, hot plate, and writhing methods. The results of this in vivo study revealed several compounds as potent analgesic agents among which compound 6e showed significant analgesic effect for all the three assays employed