Predictors of Frailty in Patients With Liver Cirrhosis.

Introduction Frailty is noticed in a large number of cirrhotic patients with advanced liver disease. Frailty not only disposes cirrhotic patients to increased rates of decompensation and hospitalization but also leads to prolonged hospital stay and increased psychological and social impact, resulting in the delisting of these patients from the transplant list. Therefore, our aim was to identify the factors that are independent predictors of frailty in patients with liver cirrhosis. Methods This cross-sectional study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from March 1, 2022, to August 31, 2022. All the patients diagnosed with liver cirrhosis and aged 18-70 years were included in the study. The excluded patients comprised those with disorders that over-estimate frailty such as cardiopulmonary disease and hepatocellular carcinoma. The measurement of the Liver Frailty Index (LFI) was done using the hand grip strength method, timed chair stands, and balance testing. Patients with LFI >4.5 were considered frail. All data was entered and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, New York, United States). Continuous variables were analyzed using the student-t test while categorical variables were analyzed using the chi-square test. Variables with significance on univariate analysis then underwent multivariate analysis to identify the independent predictors of frailty in cirrhotic patients. A p-value < 0.05 was considered statistically significant. Results A total of 132 patients were included in the study. Out of them, 89 (67.4%) were males. On assessment, 51 (38.6%) patients were frail on presentation. On univariate analysis, female gender, advanced age, raised total leucocyte count, increased percentage of neutrophils on peripheral smear, raised serum creatinine, raised total bilirubin, raised prothrombin time, high Child Turcotte Pugh (CTP) score, and high model for end-stage liver disease along with low hemoglobin and low serum albumin levels were statistically significantly associated with frailty in cirrhosis. On multivariate analysis, female gender, age >40 years, CTP>B7, Hemoglobin <10g/dl, and neutrophils >60% on peripheral smear were independent predictors of liver frailty in cirrhotic patients. Conclusion Female gender, advanced age, increased neutrophils on peripheral smear, decreased hemoglobin along with increased degree of liver dysfunction were independent predictors of increased frailty in patients with chronic liver disease.

Identification of novel benzothiazole-thiadiazole-based thiazolidinone derivative: in vitro and in silico approaches to develop promising anti-Alzheimer's agents.

Aim: The present study describes benzothiazole derived thiazolidinone based thiadiazole derivatives (1-16) as anti-Alzheimer agents. Materials & methods: Synthesis of benzothiazole derived thiazolidinone based thiadiazole derivatives was achieved using the benzothiazole bearing 2-amine moiety. These synthesized compounds were confirmed via spectroscopic techniques (1H NMR, 13C NMR and HREI-MS). These compounds were biologically evaluated for their anti-Alzheimer potential. Binding interactions with proteins and drug likeness of the analogs were explored through molecular docking and ADMET analysis, respectively. In the novel series, compound-3 emerged as the most potent inhibitor when compared with other derivatives of the series. Conclusion: The present study provides potent anti-Alzheimer's agents that can be further optimized to discover novel anti-Alzheimer's drugs.

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Recent development and strategies towards target interactions: Synthesis, characterization and in silico analysis of benzimidazole based thiadiazole as potential anti-Alzheimer agents.

In the current research study, we aim to design and synthesize highly potent hybrid analogs of benzimidazole derived thiadiazole based Schiff base derivatives which can combat the cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) accountable for developing Alzheimer's disease. In this context, we have synthesized 15 analogs of benzimidazole based thiadiazole derivatives, which were subsequently confirmed through spectroscopic techniques including 1H NMR, 13C NMR and HREI-MS. Biological investigation of all the analogs revealed their varied acetylcholinesterase inhibitory potency covering a range between 3.20 ± 0.10 µM to 20.50 ± 0.20 µM as well as butyrylcholinesterase inhibitory potential with a range of 4.30 ± 0.50 µM to 20.70 ± 0.50 µM when compared with the standard drug Donepezil having IC50 = 6.70 ± 0.20 µM for AChE and 7.90 ± 0.10 µM for BuChE. The promising inhibition by the analogs was evaluated in SAR analysis, where analog-1 (IC50 = 3.20 ± 0.10 µM for AChE and 4.30 ± 0.50 µM for BuChE), analog-4 (IC50 = 4.30 ± 0.30 µM for AChE and 5.50 ± 0.20 µM for BuChE) and analog-5 (IC50 = 4.10 ± 0.30 µM for AChE and 4.60 ± 0.40 µM for BuChE) were found as the lead candidates. Moreover, molecular docking and ADME analysis were conducted to explore the better binding interactions and drugs likeness respectively.

Facile benzothiazole-triazole based thiazole derivatives as novel thymidine phosphorylase and α-glucosidase inhibitors: Experimental and computational approaches.

The present study reports the new thiazole (A-L) derivatives based on benzothiazole fused triazole which were synthesized and assessed against thymidine phosphorylase and α-glucosidase enzymes. Several compounds with the same basic structure but different substituents were found to have high activity against the targeted enzymes, while others with the same basic skeleton but different substituents were found to have medium to low activity among the members of tested series. These analogs showed a varied range of inhibition in both case thymidine phosphorylase and alpha glucosidase, A (IC50 = 7.20 ± 0.30 µM and IC50 = 1.30 ± 0.70 µM), B (IC50 = 8.80 ± 0.10 µM and IC50 = 2.10 ± 0.30 µM), C (IC50 = 8.90 ± 0.40 µM and IC50 = 3.20 ± 0.20 µM) and thiazole containing analogs such as G (IC50 = 11.10 ± 0.20 µM and IC50 = 7.80 ± 0.20 µM) and H (IC50 = 12.30 ± 0.30 µM and IC50 = 6.30 ± 0.20 µM). When compared with standard drugs 7-Deazaxanthine, 7DX (IC50 = 10.60 ± 0.50 µM) and acarbose (IC50 = 4.30 ± 0.30 µM) respectively. These analogs were also subjected to molecular docking studies which indicated the binding interaction of molecules with active sites of the enzyme and strengthen the drug profile of these compounds. ADMET studies also predict the drug-like properties of these compounds, with no violations of drug likeness rules.

Impact of behavioral biases on investment decisions and the moderation effect of financial literacy; an evidence of Pakistan.

Th is study offers empirical insights into investor behavior and its correlation with various behavioral biases in the context of investment decisions in the Pakistan Stock Exchange (PSX). Data was collected through a structured questionnaire from 261 individual investors in Pakistan. The study employs hierarchical regression analysis to test the hypothesis. It considers several behavioral biases, and statistically, anchoring and adjustment, overconfidence, and herding show a significant impact. The study uses financial literacy to examine its moderating effects on these biases, and the result suggests that it significantly influences behavioral biases related to investment decisions. The results underscore the unique investment behaviors in emerging markets, contrasting with established norms in well-developed financial markets. These findings can inform policymakers and stock market authorities about investor decision-making in emerging economies.

In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine-thiazole hybrids derivatives as promising urease inhibitors.

The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1H NMR, 13C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC50 = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC50 = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC50 = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC50 = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.

Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents.

Benzimidazole-based pyrrole/piperidine analogs (1-26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1-13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14-26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively.

Preparation of visible-light active MOFs-Perovskites (ZIF-67/LaFeO3) nanocatalysts for exceptional CO2 conversion, organic pollutants and antibiotics degradation.

Modern industries rapid expansion has heightened energy needs and accelerated fossil fuel depletion, contributing to global warming. Additionally, organic pollutants present substantial risks to aquatic ecosystems due to their stability, insolubility, and non-biodegradability. Scientists are currently researching high-performance materials to address these issues. LaFeO3 nanosheets (LFO-NS) were synthesized in this study using a solvothermal method with polyvinylpyrrolidone (PVP) as a soft template. The LFO-NS demonstrate superior performance, large surface area and charge separation than that of LaFeO3 nanoparticles (LFO-NP). The LFO-NS performance is further upgraded by incorporating ZIF-67. Our results confirmed the ZIF-67/LFO-NS nanocomposite have superior performances than pure LFO-NP and ZIF-67. The integration of ZIF-67 has enhanced the charge separation and promote the surface area of LFO-NSwhich was confirmed by various characterization techniques including TEM, HRTEM, DRS, EDX, XRD, FS, XPS, FT-IR, BET, PL, and RAMAN. The 5ZIF-67/LFO-NS sample showed significant activities for CO2 conversion, malachite green degradation, and antibiotics (cefazolin, oxacillin, and vancomycin) degradation. Furthermore, stability tests have confirmed that our optimal sample very active and stable. Furthermore, based on scavenger experiments and the photocatalytic degradation pathways, it has been established that H+ and •O2- are vital in the decomposition of MG and antibiotics. Our research work will open new gateways to prepare MOFs-Perovskites nanocatalysts for exceptional CO2 conversion, organic pollutants and antibiotics degradation.

Diagnostic Accuracy of Narrow-Band Imaging in Predicting Helicobacter pylori Gastritis in Patients With Dyspepsia.

Background Helicobacter pylori (H. pylori) is one of the most prevalent causes of chronic gastritis that can lead to gastric cancer if left untreated. Currently, endoscopy and histology are the gold standard tests for the diagnosis of H. pylori gastritis. Recently, studies have shown the utility of narrow-band imaging (NBI) in predicting H. pylori gastritis. Therefore, we aimed to determine the diagnostic accuracy of NBI in predicting H. pylori gastritis in patients with dyspepsia. Methodology After obtaining approval from the Ethical Review Committee, Sindh Institute of Urology and Transplantation, this cross-sectional study was conducted in the outpatient Clinic of Hepatogastroenterology of the institute. Inclusion criteria involved all patients of either gender aged 18 to 65 years with dyspeptic symptoms. We excluded patients with a history of proton pump inhibitor use within two weeks before endoscopy, heart failure, previous gastrectomy, portal gastropathy, cirrhosis, use of antiplatelet medications, non-steroidal anti-inflammatory drugs or anticoagulant medication, and hemorrhagic or thrombophilia disorders. Each patient underwent endoscopy-guided NBI studies followed by biopsies from the antrum and body of the stomach. Multivariate logistic regression analysis was performed for the type of NBI pattern predicting H. pylori infection. The diagnostic accuracy was obtained individually for each NBI type and then for the presence of either two or all three NBI types in predicting H. pylori gastritis. Results Out of the total 775 patients enrolled in the study, abnormal NBI patterns were observed in 401 (51.7%) patients. The presence of abnormal NBI antral mucosal pattern on endoscopy was significantly associated with H. pylori infection (p < 0.001) with excellent diagnostic accuracy. Among the three NBI types, individually, NBI type III had excellent specificity and better diagnostic accuracy in predicting H. pylori gastritis than the other two types. Furthermore, the presence of all three abnormal NBI patterns (I+II+III) together was significantly associated with the presence of H. pylori gastritis with a sensitivity of 94.54%, specificity of 86.55%, and diagnostic accuracy of 90.32%. Conclusions NBI on endoscopy shows excellent diagnostic accuracy in identifying H. pylori gastritis in patients with dyspepsia. However, multicenter studies are required not only to validate our results but also to predict the pre-cancerous lesions on NBI in patients with H. pylori gastritis.

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that target drug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and -CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

Management of Tacrolimus-Induced Toxicity With Normal Serum Levels After Liver Transplant.

Drug-induced liver injury after liver transplant occurs in 1.7% of patients. Tacrolimus is an effective immunosuppressant that is used to treat acute rejection. Although rare, it can cause toxicity, which is demonstrated by cholestatic liver injury. Here, we present a case of a young male patient who was diagnosed with Wilson disease, had penicillaminechelating therapy, and underwent living related liver transplant. Within 1 month posttransplant, he developed deranged, predominantly cholestatic pattern liver function tests. Laboratory parameters showed total bilirubin of 1.12 mg/ dL, alanine aminotransferase of 553 IU/L, gammaglutamyltransferase of 624 IU/L, and tacrolimus level of 10.2 ng/mL. After thorough evaluation, a liver biopsy was performed. Liver biopsy showed hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. However, with normal level of tacrolimus, the biopsy was suggestive of drug-induced liver injury. Thus, tacrolimus dose was reduced, resulting in improved liver function tests and patient discharge from the hospital. Tacrolimus is an effective immunosuppressant after liver transplant and has the ability to treat early acute rejection. The patient's liver biopsy showed hepatocellular necrosis with centrilobular cholestasis without any evidence of graft rejection. Cholestatic liver injury after tacrolimus usually resolves after dose reduction or by switching to another agent. With demonstrated tacrolimus-induced toxicity in liver transplant recipients, despite normal serum levels, transplant physicians should keep high index of suspicion regarding toxicity in the posttransplant setting.

Ocular therapeutics and the profession of optometry in South Africa.

BACKGROUND:  The role of an optometrist as defined by the World Council of Optometry includes the management of ocular diseases. In 2015, the scope of optometry in South Africa was expanded to include ocular therapeutic drugs. To date approximately 27 optometrists have obtained full certification to exercise ocular therapeutic privileges. AIM:  This study aimed to determine the interest, readiness, as well as challenges, of optometrists for the inclusion of ocular therapeutics into daily practice. SETTING:  The study was set in South Africa. METHODS:  A descriptive, cross-sectional study design was employed. Convenience sampling was used to recruit 420 participants from a study population of optometrists registered with the Health Professions Council of South Africa, with data collected using an online questionnaire hosted on social media platforms and distributed by professional organisations. Data were analysed using the Statistical Package for Social Science version 27. RESULTS:  The majority of respondents (73.3%) reported keenness for ocular therapeutics certification. While 75.7% of respondents had obtained diagnostics certification, only 9.5% were registered with the Health Professions Council of South Africa (HPCSA) with ocular therapeutics certification. Most (92.1%) respondents reported the required minimum of 600 h of clinical training as a major challenge to obtaining ocular therapeutics certification. Almost all (96.9%) of the respondents agreed that ocular therapeutics certification will improve provision of optimal eyecare. CONCLUSION:  South African optometrists support and are personally interested in ocular therapeutics certification. However, while there is a preponderance of diagnostically qualified optometrists, very few are certified for ocular therapeutics with completion of the required clinical training for certification perceived as the greatest challenge.Contribution: This findings in this study highlight that, current requirements to support ocular therapeutics certification of South African optometrists should be reviewed to ensure an enabling environment for the completion of the clinical training.

A critical review on metal-organic frameworks (MOFs) based nanomaterials for biomedical applications: Designing, recent trends, challenges, and prospects.

Nanomaterials (NMs) have garnered significant attention in recent decades due to their versatile applications in a wide range of fields. Thanks to their tiny size, enhanced surface modifications, impressive volume-to-surface area ratio, magnetic properties, and customized optical dispersion. NMs experienced an incredible upsurge in biomedical applications including diagnostics, therapeutics, and drug delivery. This minireview will focus on notable examples of NMs that tackle important issues, demonstrating various aspects such as their design, synthesis, morphology, classification, and use in cutting-edge applications. Furthermore, we have classified and outlined the distinctive characteristics of the advanced NMs as nanoscale particles and hybrid NMs. Meanwhile, we emphasize the incredible potential of metal-organic frameworks (MOFs), a highly versatile group of NMs. These MOFs have gained recognition as promising candidates for a wide range of bio-applications, including bioimaging, biosensing, antiviral therapy, anticancer therapy, nanomedicines, theranostics, immunotherapy, photodynamic therapy, photothermal therapy, gene therapy, and drug delivery. Although advanced NMs have shown great potential in the biomedical field, their use in clinical applications is still limited by issues such as stability, cytotoxicity, biocompatibility, and health concerns. This review article provides a thorough analysis offering valuable insights for researchers investigating to explore new design, development, and expansion opportunities. Remarkably, we ponder the prospects of NMs and nanocomposites in conjunction with current technology.

The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline-Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents.

In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (1-17) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (1-17) were characterized using a combination of several spectroscopic techniques, including FT-IR, 1H-NMR, 13C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against α-glucosidase and urease enzymes. These analogues disclosed varying degrees of α-glucosidase and urease inhibitory activities, with their IC50 values ranging from 2.50 to 17.50 µM (α-glucosidase) and 14.30 to 41.50 (urease). Compounds 6, 7, 14, and 12, with IC50 values of 2.50, 3.20, 3.40, and 3.50 µM as compared to standard acarbose (IC50 = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC50 = 31.40 µM), respectively, showed excellent inhibitory activity. The structure-activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound 6 was a dual potent inhibitor against α-glucosidase and urease due to the presence of -CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC50 values. Moreover, in silico studies on most active compounds, i.e., 6, 7, 14, and 12, were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes.

Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer's Candidates.

A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1-17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied range of inhibitory activities having IC50 values ranging from 0.86 ± 0.33 µM to 26.73 ± 0.84 µM (AChE) and 0.89 ± 0.12 µM to 27.08 ± 0.19 µM (BuChE), respectively. The results obtained were compared with standard Donepezil drugs (IC50 = 1.26 ± 0.18 µM for AChE) and (1.35 ± 0.37 µM for BuChE), respectively. Specifically, the derivatives 1-17, 1, 9, and 14 were found to be significantly active, with IC50 values of 0.86 ± 0.30, 0.92 ± 0.10, and 1.10 ± 0.37 µM (against AChE) and 0.89 ± 0.12, 0.98 ± 0.48 and 1.19 ± 0.42 µM (against BuChE), respectively.The structure-activity relationship (SAR) studies revealed that derivatives bearing para-CF3, ortho-OH, and para-F substitutions on the phenyl ring attached to the thiadiazole skeleton, as well as meta-Cl, -NO2, and para-chloro substitutions on the phenyl ring, having a significant effect on inhibitory potential. The synthesized scaffolds have been further characterized by using 1H-NMR, 13C-NMR, and (HR-MS) to confirm the precise structures of the synthesized compounds. Additionally, the molecular docking approach was carried out for most active compounds to explore the binding interactions established by most active compounds, with the active sites of targeted enzymes and obtained results supporting the experimental data.

Investigation of novel bis-thiadiazole bearing schiff base derivatives as effective inhibitors of thymidine phosphorylase: Synthesis, in vitro bioactivity and molecular docking study.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It is crucial for the development, invasion and metastasis of tumors as well as angiogenesis. In our current research, we examine how structurally changing bis-thiadiazole bearing bis-schiff bases affects their ability to inhibit TP. Through the oxidative cyclization of pyridine-based bis-thiosemicarbazone with iodine, a series of fourteen analogs of bis-thiadiazole-based bis-imines with pyridine moiety were developed. Newly synthesized scaffolds were assessed in vitro for their thymidine phosphorylase inhibitory potential and showed moderate to good inhibition profile. Eleven scaffolds such as 4a-4d,4f-4 h and 4j-4 m were discovered to be more effective than standard drug at inhibiting the thymidine phosphorylase enzyme with IC50 values of 1.16 ± 1.20, 1.77 ± 1.10, 2.48 ± 1.30, 12.54 ± 1.60, 14.63 ± 1.70, 15.53 ± 1.80, 17.47 ± 1.70, 18.98 ± 1.70, 19.53 ± 1.50, 22.73 ± 2.40 and 24.87 ± 2.80 respectively, while remaining three analogs such as 4n, 4i and 4ewere found to be more potent, but they were less potent than the standard drug. All analogs underwent SAR studies based on the pattern of substitutions around the aryl part of the bis-thiadiazole skeleton. The most active analogs in the synthesized series were then molecular docking study performed to investigate their interactions of active part of enzyme. The results showed that remarkable interactions were exhibited by these analogs with the targeted enzymes active sites. Furthermore, to confirm the structure of synthesized analogs by employing spectroscopic tools such as HREI-MS and NMR.

Design, Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Study of Benzimidazole-Based Oxazole Analogues: A Promising Acetylcholinesterase and Butyrylcholinesterase Inhibitors.

Alzheimer's disease (AD) is a degenerative neurological condition that severely affects the elderly and is clinically recognised by a decrease in cognition and memory. The treatment of this disease has drawn considerable attention and sparked increased interest among the researchers in this field as a result of a number of factors, including an increase in the population of patients over time, a significant decline in patient quality of life, and the high cost of treatment and care. The current work was carried out for the synthesis of benzimidazole-oxazole hybrid derivatives as efficient Alzheimer's inhibitors and as a springboard for investigating novel anti-chemical Alzheimer's prototypes. The inhibition profiles of each synthesised analogue against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were assessed. All the synthesized benzimidazole-based oxazole analogues displayed a diverse spectrum of inhibitory potentials against targeted AChE and BuChE enzymes when compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 M and 4.50 ± 0.11 µM, respectively). The most active AChE and BuChE analogues were discovered to be analogues 9 and 14, with IC50 values of 0.10 ± 0.050 and 0.20 ± 0.050 µM (against AChE) and 0.20 ± 0.050 and 0.30 ± 0.050 µM (against BuChE), respectively. The nature, number, position, and electron-donating and -withdrawing effects on the phenyl ring were taken into consideration when analysing the structure-activity relationship (SAR). Molecular docking studies were also carried out on the active analogues to find out how amino acids bind to the active sites of the AChE and BuChE enzymes that were being studied.

Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease.

A series of benzimidazole-based Schiff base derivatives (1-18) were synthesized and structurally elucidated through 1H NMR, 13C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC50 value in the range of 123.9 ± 10.20 to 342.60 ± 10.60 µM and BuChE in the range of 131.30 ± 9.70 to 375.80 ± 12.80 µM in comparison with standard Donepezil, which has IC50 values of 243.76 ± 5.70 µM (AChE) and 276.60 ± 6.50 µM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure-activity relationship of the synthesized derivatives.

Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach.

A new series of thiazole derivatives (4a-p) incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds 4a (docking score = -13.45), 4g (docking score = -12.87), 4o (docking score = -12.15), and 4p (docking score = -11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC50 values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds 4a and 4o emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as 1H-NMR, 13C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined.