SYNTHESIS, INSILICO DOCKING AND ADMET STUDIES OF ARYL ACETIC ACID DERIVATIVES AS PROSTAGLANDIN ENDOPEROXIDE H SYNTHASE-2 INHIBITORS

Objectives: To study the inhibition of prostaglandin endoperoxide H synthase-2 (PHSH-2) for arylacetic acid derivatives. Methods: This study was performed to evaluate the anti-inflammatory activity of the synthesized arylacetic acid erivatives through molecular docking via Discovery Studio 4.0 and Schrodinger Software. ADMET study was conducted to find the assessment on genotoxicology.Results: The synthesized arylacetic acid derivatives were confirmed by nuclear magnetic resonance, liquid chromatography-mass spectrometry, and purity by high-performance liquid chromatography. The synthetic pathway is economical, industrial scalability and is achieved with high yield and purity. The in silico studies identified the active pocket and compared with the standard drug.Conclusion: Results from this work conclude that the arylacetic acid derivatives have very good inhibition and very low binding energy toward the active pocket, hence can be considered as good inhibitors of PHSH-2 on comparison with iodosuprofen. The compounds qualified Lipinski rule of five and the ADMET results were non-mutagenic and non-carcinogenic.Keywords: Arylacetic acid, 1 phenyl glycidyl ether protein, ADMET, In silico docking, Anti-inflammatory

The role of patient perspectives in forensic mental health: a study of progress in recovery and protective factors of risk for violence

The assessment of violence risk and progress in recovery are prominent concerns in forensic psychiatry, with protective factors being recently incorporated in understanding the risk and recovery paradigm. However, there are still very few assessment tools that incorporate the patient perspective in forensic psychiatry. The following thesis explored patient self-assessments of protection and progress in recovery and assessed the degree of concordance with clinician and research-rated estimates of these constructs in a sample of 37 patients deemed Not Criminally Responsible for their crimes on account of mental disorder (NCRMD). Patient file reviews, patient-rated scales, clinician-rated scales and patient interviews were used to rate protective factors and risk factors for violence risk, and progress in recovery. Linear regression models revealed that work and education experience, criminal history and psychiatric history were not predictive of patient-clinician and patient-researcher concordance of protective factors for violence risk (SAPROF) and progress in recovery (DUNDRUM-3 and DUNDRUM-4). Criminal history alone was predictive of risk scores (HCR-20) and protection scores (SAPROF). Binary logistic regressions indicated that the aforementioned concordance was not significant in predicting whether a patient was assigned to a medium secure or general secure unit. A hierarchical binary logistic regression showed that protection scores did not provide additive validity to risk scores in predicting the level of security of patients. Implications and limitations are discussed. This study increases the understanding of protective factors for violence risk and progress in recovery, with an emphasis on patient perceptions and their concordance with the clinicians’ and researchers’ perceptions.</p

Ru(II)-Catalyzed [4 + 2]-Annulation of 2‑Alkenyl/Arylimidazoles with <i>N-</i>Substituted Maleimides and 1,4-Naphthoquinones: Access to Imidazo-Fused Polyheterocycles

Synthesis of imidazo-fused polyheterocyclic molecular frameworks, viz. imidazo[1,2-a]pyrrolo[3,4-e]pyridines, imidazo[2,1-a]pyrrolo[3,4-c]isoquinolines, and benzo[g]imidazo[1,2-a]quinoline-6,11-diones, has been achieved by the ruthenium(II)-catalyzed [4 + 2] C–H/N–H annulation of 2-alkenyl/2-arylimidazoles with N-substituted maleimides and 1,4-naphthoquinones. The developed protocol is operationally simple, exhibits broad substrate scope with excellent functional group tolerance, and provides the desired products in moderate to good yields. The mechanistic studies suggest that the reaction involves the formation of a C–C bond through Ru-catalyzed C(sp2)–H bond activation followed by intramolecular cyclization

Ru(II)-Catalyzed [4 + 2]-Annulation of 2‑Alkenyl/Arylimidazoles with <i>N-</i>Substituted Maleimides and 1,4-Naphthoquinones: Access to Imidazo-Fused Polyheterocycles

Synthesis of imidazo-fused polyheterocyclic molecular frameworks, viz. imidazo[1,2-a]pyrrolo[3,4-e]pyridines, imidazo[2,1-a]pyrrolo[3,4-c]isoquinolines, and benzo[g]imidazo[1,2-a]quinoline-6,11-diones, has been achieved by the ruthenium(II)-catalyzed [4 + 2] C–H/N–H annulation of 2-alkenyl/2-arylimidazoles with N-substituted maleimides and 1,4-naphthoquinones. The developed protocol is operationally simple, exhibits broad substrate scope with excellent functional group tolerance, and provides the desired products in moderate to good yields. The mechanistic studies suggest that the reaction involves the formation of a C–C bond through Ru-catalyzed C(sp2)–H bond activation followed by intramolecular cyclization