Facile Integration of Hanztsch's Switch-Off/On Modeled Fluorogenic Probe for Feasible Tagging and Tracking of the Midodrine Drug in Different Matrices; First Evaluation of the Method's Greenness, Whiteness, Blueness, Quantum Yield, and Tablets' Content Homogeneity.

The proposed investigation follows a certain methodology to guarantee that the procedure employed is sustainable and green. It is noteworthy to mention that various tools have been implemented as potential indicators of environmental sustainability (greenness and whiteness). From a novelty viewpoint, a new tool, BAGI, for the method's blueness evaluation was applied to the planned method and showed a high applicability score. Fortunately, the WAC concept, which combines ecological and functional variables using the Green/Red/Blue design (RBG 12 tool), identifies the established analytical approach as white. In the planned study, a new, green, simple, nano-trace-sensitive, original fluorimetric methodology was established to analyze and assess midodrine hydrochloride content in different matrices. Midodrine's primary amine moiety reacts with Diacetylmethane/Oxymethylene reagent in an acetate buffer, which leads to generating a fluorescent dihydrolutidine derivative (Hantzsch-named reaction). Consequently, the signal strength of this compound was quantified at 487 nm, with an excitation wavelength of 426 nm. This analysis indicated that the technique exhibited linearity within the range of 0.05 to 1.1 µg mL-1 concentrations, accompanied by remarkably good sensitivity values (LOD and LOQ). The methodology employed in this examination was subjected to validation following the rules recognized by ICH. From the perspective of pharmacy and chemistry, the method presented in this study was successfully employed to analyze commercially available tablets, oral drops, and human fluids. The outcomes obtained demonstrated satisfactory recovery rates without any interference from excipients. Following the USP recommendations, the intended technique was finally implemented to explore the content homogeneity evaluation.

Efficient application of Pyrosin B for nano-gram level assay of antiparkinsonian medication, rasagiline: Evaluation of tablets and content uniformity.

Rasagiline (RAS) is a medication for Parkinson's disease that increases dopamine levels in the brain by inhibiting monoamine oxidase, helping to alleviate symptoms. The proposed study aims to develop an efficient, feasible, and sensitive method for RAS assay, utilizing Pyrosin B dye, a convenient fluorescent ligand. Combining the RAS analyte with Pyrosin B ligand in a mildly acidic buffered solution rapidly quenches the native fluorescence of the ligand. This quenching results from the formation of a specific ion-dipole association complex between the lone pair-bearing atoms of the ligand and the protonated amine moiety of RAS, highlighting their interactive chemistry under these conditions. The degree of this interaction demonstrated superior sensitivity compared with reported alternatives, exhibiting a linear range of 50.0 to 1000.0 ng/mL. The method is characterized by a limit of detection (LOD) of 16.0 ng/mL and a limit of quantification (LOQ) of 48.0 ng/mL. By optimizing the RAS-Pyrosin B system, the variable parameters were finely tuned, ensuring the assay method's reliability. The method's accuracy, precision, selectivity, and robustness were validated according to International Council for Harmonization (ICH) guidelines, enabling precise and efficient analysis of RAS in the nanogram range. This method streamlines the analysis procedure and reduces environmental impact, making it a promising approach for the quality control of ParkintreatR tablets (1 mg) and other analytical applications.

Dual benefits of NBD-Cl fluorogenic action and sample pretreatment (SALLE) technology in the assessment of anticoagulant medication: Dabigatran in pharmaceutical capsules and plasma samples.

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8 nm and by adjustment of a wavelength of 474.7 nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5 ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.

An ingenious technique based on the usage of fluorone-based dye; pyrosin B in prucalopride assay in different matrices through an "on-off" dye native fluorescence probe.

Prucalopride (PCD), is a modern medication approved by the United States in 2018 to alleviate constipation caused by motility issues. PCD demonstrates a strong affinity and selectivity toward the 5-HT4 receptor. The study here introduces a feasible, direct, non-extractive, and affordable pathway for PCD analytical tracking. The fluorimetric study is based on the on-off effect on the emission amplitude of fluorone-based dye (pyrosin B). In a one-pot experiment, the complex between PCD and pyrosin B is formed instantly in an acidic medium. Correlation between decreased pyrosin B emission and PCD concentrations provides a linear calibration plot from 50 to 900 ng/mL. PCD-dye complex system affecting variables were meticulously tuned. The values of the estimated limit of quantitation and limit of detection for the current methodology were 47.5 and 15.7 ng/mL, respectively. Conformity of the strategy validity was achieved by a comprehensive study of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use criteria. The method was convincingly applied for PCD assay in tablets and content uniformity investigation. Furthermore, PCD tracking in the spiked biological fluid was applied. Finally, the method uses distilled water as dispersing medium which rise accommodation with the green chemistry principle.

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

Formulation of silymarin surface modified vesicles: In vitro characterization to cell viability assessment.

Silymarin (SLR) is a poorly water-soluble bioactive compound with a wide range of therapeutic activities. Nanosized silymarin vesicles (F1-F6) were prepared by the solvent evaporation rehydration method. The silymarin vesicles were evaluated for vesicle size, surface charge, entrapment efficiency, and drug release studies. The optimized SLR lipid vesicle (F3) was further modified with the addition of the cationic polymer chitosan. After that, the modified vesicle (F3C1) was assessed for permeation flux, antimicrobial activity, cell viability, and molecular docking studies. The silymarin vesicles showed nanometric size (<250 nm), low polydispersibility index (<0.05), negative surface charge, and high SLR entrapment (85-95 %). The drug release study result demonstrated a maximum drug release of 91.2 ± 2.8 %. After adding chitosan to the surface, there was a significant change in the size, polydispersibility index, surface charge (positive), and encapsulation efficiency. The drug release was found to be prolonged, and the permeation flux was also increased in comparison to free SLR. A comparative antimicrobial result was observed in comparison to the free SLR and standard drug. The cell viability assay also demonstrated a low IC50 value for F3C1 against the cell line.

Development of topical silver nano gel formulation of Bixin: Characterization, and evaluation of anticancer activity.

Objective: Skin cancer refers to the pathological condition characterized by the proliferation of atypical skin cells in an uncontrolled manner. Plant-based products such as bixin although show promising anticancer properties, but maintaining their stability in a formulation is a difficult task. The objective of the research is to formulate a silver nanoparticle gel preparation of bixin and evaluate its anticancer properties. Methods: The extract from Bixa orellana seed was prepared by hot extraction technique to isolate the active ingredient, bixin. A green synthesis approach was utilized for preparing the silver nanoparticle gel of bixin (BOAgNPs). Characterization of silver nanoparticles was done using FTIR, scanning electron microscopy, compatibility study, homogeneity testing, pH evaluation, and drug content determination. The in-vitro anticancer activity was performed using cell lines (B16F10) and in-vivo by chemical carcinogen (7,12-dimethylbenz (a) anthracene) in mice. Results: The BOAgNPs-loaded topical gel was found to be homogeneous (clear orange color) and pH-compatible (pH ≈ 6.66) with the skin. The characterization studies indicated the presence of all functional groups in the formulation. An optimized batch of bixin-nano gel showed about 60% inhibitory effects on B16F10 cell lines (in-vitro activity) when equated with a reference drug, 5-fluorouracil. The in-vivo anticancer study suggested suppression of tumorigenesis and promotion of the healing process with bixin-nano gel application on the skin. Conclusion: The results suggested the promising anticancer property of bixin when formulated in silver nanoparticle gel. The preparation of silver particles nano gel with bixin might provide an effective alternative option for treating skin cancers, provided more research complements the findings of the present study.

Dissolution enhancement of Gefitinib by solid dispersion and complexation with ß-cyclodextrins: In vitro testing, cytotoxic activity, and tablet formulation.

Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-ß-cyclodextrin (MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22-2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP-GEF (1:4 w/w) and MßCD-GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC50 values of the PVP-GEF and MßCD-GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p < 0.05) than free GEF. In addition, the formulated tablets exhibited enhanced dissolution compared to pure GEF tablets. PVP-GEF SD tablets released (35.1 %±0.4) of GEF after one hour, while GEF-MßCD tablets released (42.2 % ± 0.7) after one hour. In the meantime, tablets containing pure GEF showed only 15 % ± 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

Engineering processive cellulase of Clostridium thermocellum to divulge the role of the carbohydrate-binding module.

The processive cellulase (CelO) is an important modular enzyme of Clostridium thermocellum. To study the effect of the carbohydrate-binding module (CBM3b) on the catalytic domain of CelO (GH5), four engineered derivatives of CelO were designed by truncation and terminal fusion of CBM3b. These are CBM at the N-terminus, native form (CelO-BC, 62 kDa); catalytic domain only (CelO-C, 42 kDa); CBM at the C-terminus (CelO-CB, 54 kDa) and CBM attached at both termini (CelO-BCB, 73 kDa). All constructs were cloned into pET22b (+) and expressed in Escherichia coli BL21 (DE3) star. The expression levels of CelO-C, CelO-CB, CelO-BC, and CelO-BCB were 35%, 35%, 30%, and 20%, respectively. The enzyme activities of CelO-C, CelO-CB, CelO-BC, and CelO-BCB against 1% regenerated amorphous cellulose (RAC) were 860, 758, 985, and 1208 units per µmole of the enzyme, respectively. The enzymes were partially purified from the lysate of E. coli cells by heat treatment followed by anion exchange FPLC purification. Against RAC, CelO-C, CelO-CB, CelO-BC, and CelO-BCB showed KM values of 32, 33, 45, and 43 mg⋅mL-1 and Vmax values of 3571, 3846, 3571, and 4545 U⋅min-1 , respectively. CBM3b at the N-terminus of GH5 linked through a P/T-rich linker was found to enhance the catalytic activity and thermostability of the enzyme.

Promising biomarkers and therapeutic targets for the management of Parkinson's disease: recent advancements and contemporary research.

Parkinson's disease (PD) is one of the progressive neurological diseases which affect around 10 million population worldwide. The clinical manifestation of motor symptoms in PD patients appears later when most dopaminergic neurons have degenerated. Thus, for better management of PD, the development of accurate biomarkers for the early prognosis of PD is imperative. The present work will discuss the potential biomarkers from various attributes covering biochemical, microRNA, and neuroimaging aspects (α-synuclein, DJ-1, UCH-L1, ß-glucocerebrosidase, BDNF, etc.) for diagnosis, recent development in PD management, and major limitations with current and conventional anti-Parkinson therapy. This manuscript summarizes potential biomarkers and therapeutic targets, based on available preclinical and clinical evidence, for better management of PD.

A practical method for oral administration of isotretinoin in pediatric oncology patient: A case study of neuroblastoma.

INTRODUCTION: Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only. CASE REPORT: A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug. MANAGEMENT AND OUTCOMES: The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass. DISCUSSION: To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended.

An integrative analytical approach designed for feasible tranexamic acid assay using o-phthalaldehyde as a fluorogenic probe: applications to tablets, ampoules, and urine.

Antifibrinolytic tranexamic acid (TRX) suppresses plasminogen activation to plasmin in a competitive way. TRX is approved for the management of heavy menstrual periods, hereditary angioedema, hemophilia, postpartum hemorrhage, surgery, tooth extraction, and severe blood loss after acute trauma. Here, the practical use of an isoindole derivative was established for a novel, easy-to-use, and affordable TRX assay. In the presence of a molecule containing a sulfhydryl group (2-mercaptoethanol) 0.02% v/v, the primary amine moiety in TRX allows its combination with o-phthalaldehyde to produce a luminous product. Excitation (338.8 nm) and emission (433.9 nm) wavelengths were used to monitor the isoindole fluorophore yield, and each operational variable was carefully examined and adjusted. The calibration graph was constructed with fluorescence intensity versus TRX concentration, excellent linearity was observed at concentrations between 40 and 950 ng/ml, and limit of detection and limit of quantitation were 41.3 and 13.6 ng/ml, respectively. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were used to validate the method. The developed method for TRX assay in various dosage forms and urine was successfully implemented and was shown to be an effective, simple, and quick replacement for the TRX assay in clinical trials and quality control.

A highly sensitive micelle-enhanced synchronous spectrofluorimetric determination of the recently approved co-formulated drugs, bilastine and montelukast in pharmaceuticals and human plasma at nanogram levels.

In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a quick, sensitive, environmentally friendly, and reasonably priced synchronous fluorescence spectroscopic approach for the first time. Enhancement of the method's sensitivity down to nanogram levels was achieved by the addition of sodium dodecyl sulfate (1.0% w/v) as a micellar system. According to the results, bilastine and montelukast's fluorescence was measured at 255.3 and 355.3 nm, respectively, using Δλ of 40.0 nm and distilled water as a green diluting solvent. With respect to the concentration ranges of bilastine (5.0-300.0 ng/ml) and montelukast (50.0-1000.0 ng/ml), the method showed excellent linearity (r ≥ 0.9998). The results showed that the suggested method is highly sensitive, with detection limits of 1.42 and 13.74 ng/ml for bilastine and montelukast, respectively. Within-run precisions (intra- and interday) per cent relative standard deviations (RSD) for both analytes were <0.59%. With high percentage recoveries and low percentage RSD values, the designed approach was successfully applied for the simultaneous estimation of the cited medications in their dosage form and human plasma samples. To evaluate the green profile of the suggested method, an analytical GREENNESS metric approach (AGREE) and green analytical procedure index (GAPI) metric tools were used. These two methods for evaluating greenness confirmed that the developed method met the highest number of green requirements, recommending its use as a green substitute for the routine analysis of the studied drugs. The proposed approach was validated according to ICHQ2 (R1) guidelines.

Solubility and Thermodynamic Analysis of Isotretinoin in Different (DMSO + Water) Mixtures.

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H2O) (2)} combinations were studied at 298.2-318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the "van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". In mixtures of {(DMSO (1) + H2O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10-1 at 318.2 K) and lowest in pure H2O (3.14 × 10-7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was "endothermic and entropy-driven" in all of the {(DMSO (1) + H2O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H2O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H2O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H2O.

Solubility and Thermodynamics Data of Cabozantinib Malate in Various Aqueous Solutions of Dimethyl Sulfoxide at Different Temperatures.

Cabozantinib malate (CBZM), a new anticancer medication, has been studied for its solubility and thermodynamic properties in a variety of {dimethyl sulfoxide (DMSO) + water (H2O)} mixtures at 298.2-318.2 K and 101.1 kPa. Using the shake flask technique, the solubility of CBZM was assessed and the results were correlated to the van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models. There was a significant correlation between the experimental CBZM solubility data and all computational models, as evidenced by the error values for all computational models being less than 5.0%. Temperature and DMSO mass percentage improved the CBZM mole fraction solubility in the cosolvent solutions of {DMSO + H2O}. At 318.2 K, pure DMSO had the highest mole fraction solubility of CBZM (4.38 × 10-2), whereas pure H2O had the lowest mole fraction solubility (2.24 × 10-7 at 298.2 K). The positive values of computed thermodynamic parameters indicated that the dissolution of CBZM was endothermic and entropy-driven in all of the {DMSO + H2O} solutions investigated. It was found that the CBZM solvation in {DMSO + H2O} solutions is governed by enthalpy. When compared to CBZM-H2O, CBZM-DMSO showed the highest molecular interactions. The findings of this investigation demonstrated that DMSO has a great deal of potential for CBZM solubilization in H2O.

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents.

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, ß-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future.

Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Neuroprotectant Effects of Hibiscetin in 3-Nitropropionic Acid-Induced Huntington's Disease via Subsiding Oxidative Stress and Modulating Monoamine Neurotransmitters in Rats Brain.

BACKGROUND: Previously reported data suggest that hibiscetin, isolated from roselle, contains delphinidin-3-sambubioside and cyanidin-3-sambubioside including anthocyanidins and has a broad range of physiological effects. In this study, we aim to analyze the effect of hibiscetin neuroprotective ability in rats against 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD). METHODS: To investigate possible toxicities in animals, oral acute toxicity studies of hibiscetin were undertaken, and results revealed the safety of hibiscetin in animals with a maximum tolerated dose. Wistar rats were divided into four groups (n = 6); (group-1) treated with normal saline, (group-2) hibiscetin (10 mg/kg) only, (group-3) 3-NPA only, and (group-4) 3-NPA +10 mg/kg hibiscetin. The efficacy of hibiscetin 10 mg/kg was studied with the administration of 3-NPA doses for the induction of experimentally induced HD symptoms in rats. The mean body weight (MBW) was recorded at end of the study on day 22 to evaluate any change in mean body weight. Several biochemical parameters were assessed to support oxidative stress (GSH, SOD, CAT, LPO, GR, and GPx), alteration in neurotransmitters (DOPAC, HVA, 5-HIAA, norepinephrine, serotonin, GABA, and dopamine), alterations in BDNF and cleaved caspase (caspase 3) activity. Additionally, inflammatory markers, i.e., tumor necrosis factor alpha (TNF-α), interleukins beta (IL-1ß), and myeloperoxidase (MPO) were evaluated. RESULTS: The hibiscetin-treated group exhibits a substantial restoration of MBW than the 3-NPA control group. Furthermore, 3-NPA caused a substantial alteration in biochemical, neurotransmitter monoamines, and neuroinflammatory parameters which were restored successfully by hibiscetin. CONCLUSION: The current study linked the possible role of hibiscetin by offering neuroprotection in experimental animal models.

A Novel Approach for the Availability and Ocular Delivery of Tenoxicam Potassium: Synthesis, Characterization, and In Vivo Application.

Tenoxicam (TX) is a non-steroidal anti-inflammatory agent that can be used to control pain in various ophthalmic lesions like cataracts, refractive surgery, and corneal abrasion. TX has a very slightly aqueous solubility of 0.072 mg/mL resulting in difficulty to be formulated in ophthalmic solutions. This study aims to improve TX solubility by converting it into its potassium salt to achieve a target of 10 mg/mL (1%w/v) concentration of TX in the desired aqueous medium for the formulation of aqueous ophthalmic solutions. The synthesized TX salt was characterized by different evaluation parameters such as solubility studies, 1H NMR, IR, and elemental analyses. Different TX potassium solutions were formulated at concentrations of 0.5% and 1% w/v using different viscosity-imparting agents. The prepared solutions were characterized for their physicochemical properties including visual inspection, pH, rheological, in vitro release, and kinetic behavior. Also, the formulations were biologically evaluated in vivo using male albino rabbits. The obtained results showed the successful synthesis of TX salt, as indicated by IR and NMR, and elemental analysis. The solubility study showed that the solubility of TX was improved hugely to 18 mg/mL (250-fold). In addition, the results showed that the prepared formulations showed acceptable physicochemical properties. The highest release rate was obtained with formula F1, which contains no viscosity-imparting agents. While as, the lowest release rate was obtained in the case of formula F9, composed of Pluronic F127 (12% w/v). The in vivo results showed that TX optimized ophthalmic solutions F8 and F9 inhibited the redness and edema in an extended or sustained manner.