Retraction of 'Ameliorating the Role of Aripiprazole in Memory Deficits Induced by Intracerebroventricular Streptozotocin-Induced Dementia of Alzheimer's Type'.

[This retracts the article DOI: 10.1021/acsomega.3c02550.].

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.

Anti-quorum sensing activity of poly-amidoamine dendrimer generation 5 dendrimer loaded kinase inhibitor peptide against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant concern in both healthcare and community settings, as it causes numerous infections worldwide with high morbidity and mortality rates. One promising strategy is to target the quorum sensing (QS) system of MRSA using a dendrimer loaded with kinase inhibitor peptide. The present investigation has formulated a poly-amidoamine dendrimer (PAMAM) G5 dendrimer that is loaded with Quorum Quencher (QQ) peptide, which functions as a histidine kinase inhibitor. The particle average size of the formulated G5-QQ3 complex was determined to be 276 nm, and polydispersity index values of 0.33. The MIC50 for the formulated nanoparticles was 18 µM as demonstrated by a growth assay. Furthermore, the G5-QQ3 complex was able to inhibit the hemolysis activity of the MRSA with a concentration of 10 µM, and for Staphylococcus aureus was 3 µM. The G5-QQ3 complex possesses the ability to inhibit, penetrate, and eradicate biofilm in MRSA, Staphylococcus aureus, and different agr mutants with inhibition percentages ranging from 60 to 72%. Furthermore, live/dead viability assay confirmed the ability of the formulated nanoparticles to effectively kill all strains within the biofilm structure as evidenced by a confocal microscope, and the cytotoxicity of the G5-QQ3 complex was dose-dependent (p < 0.05). against RAW 264.7 cells. In general, the study confirmed that encapsulating QQ3 peptide within PAMAM G5 dendrimer results in a potent anti-virulence and anti-bacterial action and suggests a synergistic effect. The findings of this study have significant implications for the development of new treatments for MRSA infections, which are a major public health concern.

Effect of C7-3-Peptide-Loaded Chitosan Nanoparticles Against Multi-Drug-Resistant Neisseria gonorrhoeae.

Introduction: The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. Methods: The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. Results: All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.

Cadmium exposure exacerbates immunological abnormalities in a BTBR T+ Itpr3tf/J autistic mouse model by upregulating inflammatory mediators in CD45R-expressing cells.

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by behavior, learning, communication, and social interaction abnormalities in various situations. Individuals with impairments usually exhibit restricted and repetitive actions. The actual cause of ASD is yet unknown. It is believed, however, that a mix of genetic and environmental factors may play a role in its development. Certain metals have been linked to the development of neurological diseases, and the prevalence of ASD has shown a positive association with industrialization. Cadmium chloride (Cd) is a neurotoxic chemical linked to cognitive impairment, tremors, and neurodegenerative diseases. The BTBR T+ Itpr3tf/J (BTBR) inbred mice are generally used as a model for ASD and display a range of autistic phenotypes. We looked at how Cd exposure affected the signaling of inflammatory mediators in CD45R-expressing cells in the BTBR mouse model of ASD. In this study, we looked at how Cd affected the expression of numerous markers in the spleen, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. Furthermore, we investigated the effect of Cd exposure on the expression levels of numerous mRNA molecules in brain tissue, including IFN-γ, IL-6, NF-κB p65, GM-CSF, iNOS, MCP-1, and Notch1. The RT-PCR technique was used for this analysis. Cd exposure increased the number of CD45R+IFN-γ+, CD45R+IL-6+, CD45R+NF-κB p65+, CD45R+GM-CSF+, CD45R+GM-CSF+, CD45R+iNOS+, and CD45R+Notch1+ cells in the spleen of BTBR mice. Cd treatment also enhanced mRNA expression in brain tissue for IFN-γ, IL-6, NF-κB, GM-CSF, iNOS, MCP-1, and Notch1. In general, Cd increases the signaling of inflammatory mediators in BTBR mice. This study is the first to show that Cd exposure causes immune function dysregulation in the BTBR ASD mouse model. As a result, our study supports the role of Cd exposure in the development of ASD.

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants.

In the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (1H and 13C) and HRMS analysis. The antioxidant activity of the synthesized compounds 5(a-c) and 6(a-c) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products 5c, 6b, and 6c exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC50 (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound 6c showed excellent activity at IC50 (68.97 ± 0.26 µM) in the FRAP assay. We carried out molecular docking and dynamics simulations to investigate the binding mode and stability of 5c, 6b, and 6c in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds.

Selective Stability Indicating Liquid Chromatographic Method Based on Quality by Design Framework and In Silico Toxicity Assessment for Infigratinib and Its Degradation Products.

Infigratinib, a protein kinase inhibitor employed in the therapeutic management of cholangiocarcinoma, was subjected to various stress conditions, including hydrolytic (acidic and alkaline), oxidative, photolytic, and thermal stress, in accordance with the rules established by the International Council for Harmonization. A cumulative count of five degradation products was observed. The application of the Quality by Design principle was utilized in the development of a rapid and specific separation method for Infigratinib and its degradation products. The methodology employed in this study was derived from an experimental design approach, which was utilized to examine the critical process parameters associated with chromatographic systems. The reversed-phase high-performance liquid chromatography technique, employing a C18 column and a mobile phase composed of a gradient mixture of 25 mM ammonium acetate buffer at pH 6.0 and acetonitrile, successfully facilitated the chromatographic separation. The methodology was expanded to include the utilization of UPLC-quadrupole tandem mass spectrometry in order to conduct a comprehensive analysis of the structural properties and characterize the degradation products. Overall, five degradation products were found in different stress conditions. The method was verified at certain working points, wherein a linearity range (5.0-200.0 µg/mL) was developed and other parameters such as accuracy, repeatability, selectivity, and system suitability were evaluated. Finally, the toxicity and mutagenicity of Infigratinib and its degradation products were predicted using in silico software, namely DEREK Nexus® (version 6.2.1) and SARAH Nexus® (version 3.2.1). Various toxicity endpoints, including chromosomal damage, were predicted. Additionally, two degradation products were also predicted to be mutagenic.

Macromolecules: Synthesis, antimicrobial, POM analysis and computational approaches of some glucoside derivatives bearing acyl moieties.

Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable antifungal and antibacterial efficacy. The synthesized derivatives showed minimum inhibitory concentration (MIC) values ranging from 0.75 µg/mL to 1.50 µg/mL and minimum bactericidal concentrations (MBCs) ranging from 8.00 µg/mL to 16.00 µg/mL. Compound 6 inhibited Ehrlich ascites carcinoma (EAC) cell proliferation by 10.36% with an IC50 of 2602.23 µg/mL in the MTT colorimetric assay. The obtained results were further rationalized by docking analysis of the synthesized derivatives against 4URO and 4XE3 receptors to explore the binding affinities and nonbonding interactions of MGP derivatives with target proteins. Compound 6 demonstrated the potential to bind with the target with the highest binding energy. In a stimulating environment, a molecular dynamics study showed that MGP derivatives have a stable conformation and binding pattern. The MGP derivatives were examined using POM (Petra/Osiris/Molinspiration) bioinformatics, and as a result, these derivatives showed good toxicity, bioavailability, and pharmacokinetics. Various antifungal/antiviral pharmacophore (Oδ-, O'δ-) sites were identified by using POM investigations, and compound 6 was further tested against other pathogenic fungi and viruses, such as Micron and Delta mutants of SARS-CoV-2.

Development of Novel Multifunctional Electroactive, Self-Healing, and Tissue Adhesive Scaffold To Accelerate Cutaneous Wound Healing and Hemostatic Materials.

Designing a multifunctional conducting hydrogel wound dressing of suitable mechanical properties, adhesiveness, self-healing, autolytic debridement, antibacterial properties, and radical scavenging ability, as well as retaining an appropriate level of moisture around the wound is highly desirable in clinical application for treating cutaneous wounds healing. Here, we designed a novel class of electroactive hydrogel based on thiol-functionalized silver-graphene oxide nanoparticles (GO/Ag/TGA) core polyaniline (PANI) shell GO/Ag/TGA/PANI nanocomposites. Thus, a series of physically cross-linked hydrogel based on GO/Ag/TGA/PANI and poly(vinyl alcohol) (PVA) was prepared by freeze-thawing method. The hydrogel was characterized by XRD, UV, FTIR, TGA, TEM, SEM, Raman spectroscopy, cyclic voltammetry (CV), and four probes test. The hydrogel showed favorable properties such as excellent tensile strength, suitable gelation time (30-56 s), tunable rheological properties (G' ∼ 1 kPa), adhesiveness, and interconnected porous structure (freeze-dried). Besides this, the hydrogel also exhibits excellent exudate uptake capacity (10.4-0.2 g/g), high swelling ratio (72.4 to 93.5%), long-term antibacterial activity against multidrug-resistant (MDR) bacterial isolates, promising antioxidant (radical scavenging) efficiency, keeping the wound moisturized, prominent hemostatic efficiency, and fast self-healing ability to bear deformation. Interestingly, in vivo experiments indicated that electroactive hydrogels can significantly promote the healing rate of artificial wounds in rats, and histological analysis by H&E reveals higher granulation tissue thickness, collagen deposition, hair follicles, dermal papillary, keratinocytes, and marked increase (P < 0.05) in hydroxyproline at the wound site during 15 days of healing of impaired wounds. On the basis of vivo and vitro assay results, it is concluded that electroactive-hydrogel-attributed multifunctional properties may serve as suitable scaffold for treating chronic wound healing and skin regeneration.

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats.

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.

Plausible Protective Role of Encephalartos villosus Extract in Acetic-Acid-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is an inflammatory ailment of the intestine associated with the upregulation of oxidative stress and pro-inflammatory cytokines. Here, we aimed to assess the consequences of Encephalartos villosus (EV) Lem extract on acetic acid (AA)-induced UC. Rats were randomly classified into five groups, as follows: control, AA, AA + mesalazine, AA + EV (50 mg/kg), and AA + EV (100 mg/kg) groups. EV (50 mg/kg and 100 mg/kg) and mesalzine (100 mg/kg) were administered orally for 14 days before the induction of UC. On the last day of the experiment, colitis was provoked via the intra-rectal delivery of 3% AA. Then, after 24 h, the rats were sacrificed and their colon tissues were isolated and inspected. Interestingly, EV pretreatment substantially (p < 0.05) reduced the elevated colon weight/length ratio and ulcer area and normalized the histological changes and immunohistochemical features. In addition, EV efficiently reduced the levels of myeloperoxidase (MPO) and increased the activity of glutathione peroxidase (GS-PX) and catalase (CAT). EV (100 mg/kg) resulted in a downregulation of toll-like receptor 4 (TLR-4) and upregulation of heme oxygenase 1 (HO-1) and occludin expression levels. Concerning the anti-inflammatory mechanisms, EV reduced the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear transcription factor kappa B (NF-ĸB) and inhibited cyclooxygenase-2 (COX-2) expression levels. It also decreased caspase-3 levels. Our results indicate that the oral intake of EV improves AA-induced colitis in rats through its antioxidative effects and the modulation of pro-inflammatory cytokines, as well as the restoration of mucosal integrity. Consequently, EV may be an efficient therapeutic candidate for UC.

Effects of Rosmarinus officinalis L. Extract on Neurobehavioral and Neurobiological Changes in Male Rats with Pentylenetetrazol-Induced Epilepsy.

This study investigated the effect of Rosmarinus officinalis L. (RO) extract on neurobehavioral and neurobiological changes in male rats with pentylenetetrazol (PTZ)-induced epilepsy. Rats were assigned into five groups: (1) control rats, (2) RO-treated rats, (3) PTZ-treated rats, (4) PTZ + RO-treated rats, and (5) PTZ + valproic acid (VA)-treated rats. The PTZ-treated rats required a significantly longer time and distance to find the platform in the Morris water maze test than the control and RO-treated rats. Additionally, PTZ-treated rats showed a decrease in tendency to cross over the platform compared to PTZ group. PTZ + RO-treated rats showed decreased swimming time and distance to find the platform compared to PTZ group. PTZ + RO-treated rats showed a significant decrease in seizure score, a reduced number of myoclonic jerks, and an increased onset of the first myoclonic jerk compared to PTZ group. PTZ reduced the time required to enter the dark room in the passive avoidance learning test, which was reversed by RO treatment. Biochemical results revealed that PTZ-treated rats had higher levels of oxidative stress markers. RO significantly increased the antioxidant markers levels and maintained normal rat brain histology. This study revealed that RO can shield the brain and neural tissues from PTZ.

Discovery of New Pyrrolo[2,3-d]pyrimidine Derivatives as Potential Multi-Targeted Kinase Inhibitors and Apoptosis Inducers.

In the pursuit of developing more potent and effective targeted kinase inhibitors (TKIs), a series of new compounds, specifically halogenated '(E)-4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N'-benzylidenebenzohydrazides', were successfully synthesized in three steps with high yields. Among these novel compounds, namely 5e, 5h, 5k, and 5l, promising cytotoxic effects were observed against four different cancer cell lines, with IC50 values ranging from 29 to 59 µM. Notably, compound 5k emerged as the most potent inhibitor, exhibiting significant activity against EGFR, Her2, VEGFR2, and CDK2 enzymes, with IC50 values ranging from 40 to 204 nM, comparable to the well-known TKI sunitinib (IC50 = 261 nM). Mechanistic investigations of compound 5k revealed its ability to induce cell cycle arrest and apoptosis in HepG2 cells, accompanied by a notable increase in proapoptotic proteins caspase-3 and Bax, as well as the downregulation of Bcl-2 activity. Furthermore, molecular docking studies indicated similar binding interactions between compound 5k and the four enzymes, as observed with sunitinib. These findings highlight the potential of compound 5k as a promising candidate for further development as a multi-targeted kinase inhibitor with enhanced potency.

Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing-Remitting EAE.

Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory autoimmune diseases. It causes the demyelination of neurons and the subsequent degeneration of the central nervous system (CNS). The infiltration of leukocytes of both myeloid and lymphoid origins from the systemic circulation into the CNS triggers autoimmune reactions through the release of multiple mediators. These mediators include oxidants, pro-inflammatory cytokines, and chemokines which ultimately cause the characteristic plaques observed in MS. Thioredoxin reductase (TrxR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling plays a crucial role in the regulation of inflammation by modulating the transcription of antioxidants and the suppression of inflammatory cytokines. The gold compound auranofin (AFN) is known to activate Nrf2 through the inhibition of TrxR; however, the effects of this compound have not been explored in a mouse model of relapsing-remitting MS (RRMS). Therefore, this study explored the influence of AFN on clinical features, TrxR/Nrf2 signaling [heme oxygenase 1 (HO-1), superoxide dismutase 1 (SOD-1)] and oxidative/inflammatory mediators [IL-6, IL-17A, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine] in peripheral immune cells and the CNS of mice with the RR type of EAE. Our results showed an increase in TrxR activity and a decrease in Nrf2 signaling in SJL/J mice with RR-EAE. The treatment with AFN caused the amelioration of the clinical features of RR-EAE through the elevation of Nrf2 signaling and the subsequent upregulation of the levels of antioxidants as well as the downregulation of oxidative/pro-inflammatory mediators in peripheral immune cells and the CNS. These data suggest that AFN may be beneficial in the treatment of RRMS.

Novel 7-Deazapurine Incorporating Isatin Hybrid Compounds as Protein Kinase Inhibitors: Design, Synthesis, In Silico Studies, and Antiproliferative Evaluation.

Cancer is a multifactorial disorder with extremely complex genetics and progression. The major challenge in cancer therapy is the development of cancer resistance and relapse. Conventional anticancer drugs directly target the DNA of the cell, while modern chemotherapeutic drugs include molecular-targeted therapy, such as targeting the abnormal cell signaling inside the cancer cells. Targeted chemotherapy is effective in several malignancies; however, the success has always been limited by drug resistance and/or side effects. Anticancer with multi-targeted actions simultaneously modulates multiple cancer cell signaling pathways and, therefore, may ease the chance of effective anticancer drug development. In this research, a series of 7-deazapurine incorporating isatin hybrid compounds was designed and successfully synthesized. Among those hybrids, compound 5 demonstrated a very potent cytotoxic effect compared to the reference anticancer drug against four cancer cell lines. Likewise, compound 5 inhibited the activity of four protein kinase enzymes in nanomolar ranges. Further analysis of the biological evaluation of compound 5 revealed the capability of compound 5 to arrest cell cycle progression and induce programmed cell death. Moreover, molecular simulation studies were performed to investigate the possible types of interactions between compound 5 and the investigated protein kinases. Finally, taking into consideration all the abovementioned findings, compound 5 could be a good candidate for further investigations.

Synthesis and In Vitro α-Amylase and α-Glucosidase Dual Inhibitory Activities of 1,2,4-Triazole-Bearing bis-Hydrazone Derivatives and Their Molecular Docking Study.

There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. The currently available antidiabetic therapies are long-term complicated and side effect-prone, and this has led to a demand for more affordable and more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. In this research work, we have focused our efforts to synthesize a series of 1,2,4-triazole-based bis-hydrazones and evaluated their antidiabetic properties. In addition, the precise structures of the synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR, and HREI-MS. To find the antidiabetic potentials of the synthesized compounds, in vitro α-glucosidase and α-amylase inhibitory activities were characterized using acarbose as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both α-amylase and α-glucosidase enzymes was due to the different substitution patterns of the substituent(s) at variable positions of both aryl rings A and B. The results of the antidiabetic assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 0.70 ± 0.05 to 35.70 ± 0.80 µM (α-amylase) and 1.10 ± 0.05 to 30.40 ± 0.70 µM (α-glucosidase). The obtained results were compared to those of the standard acarbose drug (IC50 = 10.30 ± 0.20 µM for α-amylase and IC50 = 9.80 ± 0.20 µM for α-glucosidase). Specifically, compounds 17, 15, and 16 were found to be significantly active with IC50 values of 0.70 ± 0.05, 1.80 ± 0.10, and 2.10 ± 0.10 µM against α-amylase and 1.10 ± 0.05, 1.50 ± 0.05, and 1.70 ± 0.10 µM against α-glucosidase, respectively. These findings reveal that triazole-containing bis-hydrazones act as α-amylase and α-glucosidase inhibitors, which help develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic agents.

Synthesis, Characterization, Antibacterial, Antifungal and Anticorrosion Activities of 1,2,4-Triazolo[1,5-a]quinazolinone.

The synthesis of 5,6,7,8-tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-9(4H)-one (THTQ), a potentially biologically active compound, was pursued, and its structure was determined through a sequence of spectral analysis, including 1H-NMR, 13C-NMR, IR, and HRMS. Four bacterial and four fungal strains were evaluated for their susceptibility to the antibacterial and antifungal properties of the THTQ compound using the well diffusion method. The impact of THTQ on the corrosion of mild steel in a 1 M HCl solution was evaluated using various methods such as weight loss, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) analysis. The study revealed that the effectiveness of THTQ as an inhibitor increased with the concentration but decreased with temperature. The PDP analysis suggested that THTQ acted as a mixed-type inhibitor, whereas the EIS data showed that it created a protective layer on the steel surface. This protective layer occurs due to the adsorption behavior of THTQ following Langmuir's adsorption isotherm. The inhibition potential of THTQ is also predicted theoretically using DFT at B3LYP and Monte Carlo simulation.

Synthetic transformation of 6-Fluoroimidazo[1,2-a]Pyridine-3-carbaldehyde into 6-Fluoroimidazo[1,2-a]Pyridine-Oxazole Derivatives: In vitro urease inhibition and in silico study.

Purpose: Ulcer is a serious disease that is caused due to different bacteria and over usage of various NSAIDs which caused to reduce the defensive system of stomach. Therefore, some novel series are needed to overcome these issues. Methods: Oxazole-based imidazopyridine scaffolds (4a-p) were designed and synthesized by two step reaction protocol and then subjected to urease inhibition profile (in vitro). All the newly afforded analogs (4a-p) were found potent and demonstrated moderate to significant inhibition profile. Results: Particularly, the analogs 4i (IC50 = 5.68 ± 1.66 µM), 4o (IC50 = 7.11 ± 1.24 µM), 4 g (IC50 = 9.41 ± 1.19 µM) and 4 h (IC50 = 10.45 ± 2.57 µM) were identified to be more potent than standard thiourea drug (IC50 = 21.37 ± 1.76 µM). Additionally, the variety of spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS analysis were employed to confirm the precise structures of all the newly afforded analogs. Discussion: The structure-activity relationship (SAR) studies showed that analogs possess the substitution either capable of furnishing strong HB like -OH or had strong EW nature such as -CF3 & -NO2 groups displayed superior inhibitory potentials than the standard thiourea drug. A good PLI (protein-ligand interaction) profile was shown by most active analogs when subjected to molecular study against corresponding target with key significant interactions such as pi-pi stacking, pi-pi T shaped and hydrogen bonding.

Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy.

Background: Morus alba Linn, referred to as white mulberry, is a potential traditional medicine for diabetes and neuroprotection. Aim: Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy. Material and methods: The stem Bark of M. alba was peeled and subjected to extraction. A phytoconstituent was then isolated by column chromatography and characterized using Mass spectroscopy, FTIR, and NMR. The isolated phytoconstituent was used to formulate a nanoemulsion. Nanoemulsion was also characterized for viscosity, surface tension, refractive index, pH, and particle size. Selected nanoemulsion formulations were then tested for acute oral toxicity and diabetic neuropathy, including behavioral, hematological, histopathological, and biomarker examinations. Results: The spectral analysis affirmed that the isolated compound was found to be chrysin. A nanoemulsion formulation was made using the chrysin and was characterized and found to be stable during the stability testing and fulfilled all other testing parameters. Then acute oral toxicity study of the formulations was found to be safe. Formulations were found to possess significant results against diabetic neuropathy in rats. Biomarkers were analyzed for their mechanistic involvement in reducing neuropathy in rats, and it was found that the oxidative pathway was considerably restored, suggesting that chrysin causes these effects via this pathway. Conclusions: Results suggests that isolated phytoconstituent (chrysin) from the bark of Morus alba derived nanoemulsion has protective and beneficial effects by diminishing the oxidative damage against alloxan-induced diabetic neuropathy in rats.

Ameliorating the Role of Aripiprazole in Memory Deficits Induced by Intracerebroventricular Streptozotocin-Induced Dementia of Alzheimer's Type.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder causing immense suffering for the patients. Dopamine D2 and 5-hydroxytryptamine receptor 1A (5-HT1A) receptors' activation has been reported to play a crucial role in managing neurological outcomes in the brain and other health disorders. This study aimed to investigate the role of aripiprazole, a dopamine D2 and 5-HT1A selective receptors' activator, in the restoration of memory deficit induced by streptozotocin in mice. The cognitive functions of animals were determined using the Morris water maze. Brain sections were stained with hematoxylin and eosin and Congo red to examine the structural deviations. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), acetylcholinesterase activity, IL-6, and IL-10 were measured to assess biochemical alterations. Activation of D2 and 5-HT1A with aripiprazole attenuated STZ-induced cognitive deficit, increased brain GSH levels, reduced TBARS levels, AChE activity, IL-6 levels, and IL-10 levels and prevented STZ-induced brain anomalies in mice. Hence, the present study concluded that aripiprazole mitigated STZ-induced memory impairment and can be used as an efficacious therapeutic target for the management of AD.