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This work effectively developed and validated a stability-indicating RP-HPLC technique for precisely measuring dexlansoprazole in bulk samples. An Acetonitrile and 0.5 mmol Ammonium Acetate (pH 4.5) gradient mobile phase, a 1 ml/min flow rate, and detection at 283 nm were all part of the method's unique chromatographic conditions. A Kromasil C18 column was also used. Dexlansoprazole had a 5.14-minute retention period, and the technique showed a linear range of 5-30 mg/ml with a strong correlation value of 0.997. The technique showed high sensitivity with a limit of detection (LOD) of 1.2 mg/ml and a limit of quantification (LOQ) of 3.64 mg/ml. The accuracy of the approach was shown by the percentage recovery of dexlansoprazole, which varied from 98.6% to 102%. The International Council for Harmonisation (ICH) gave standards for validating the created approach, which were followed. It covered several variables: linearity, LOD, LOQ, accuracy, precision, robustness, and solution stability. The technique demonstrated stability and the capacity to successfully separate the degradation products from the analyte peaks, establishing its validity as a stability-indicating technique. LC-MS/MS spectra were also used to establish the degradants' structures. The quantitative measurement of dexlansoprazole in bulk form may be accomplished effectively using this established RP-HPLC technique. It is a useful instrument for quality control and stability evaluation of dexlansoprazole in pharmaceutical formulations because of its accuracy, precision, and stability-indicating capabilities. [ABSTRACT FROM AUTHOR]

Stability and impurity profiling of drugs is crucial in fixed-dose drug combinations as safety, efficacy, and purity depend on an individual drug's stability behaviour. The formation of drug degradants is lean-on various factors and the probabilities of drug degradation may increase in fixed-dose drug combination formulations. Additionally, drug impurity profiling can be studied with the aid of degradation prediction. In this context, a preliminary attempt was made to use Zeneth software to anticipate the degradation of combination medications. Due to the presence of mutagenic/carcinogenic impurities i.e. NDMA/NDEA in various batches of Valsartan, FDA announces a recall in the last few years. Therefore, Zeneth predictions were performed to explore the effect of the presence of mutagenic impurity (NDMA/NDEA) on the stability of drug. The toxicity of each predicted degradant was evaluated with the help of TEST, ProTox II and Lazar toxicity prediction tools. In the present work, the stability behavior of combination drugs was evaluated with the newly developed QbD enabled UFLC method. Sacubitril and Valsartan were subjected to various stress degradation conditions like acid, base, oxidative, thermal, and photo stress environment alone and in fixed-dose combinations to assess the stability. [ABSTRACT FROM AUTHOR]

Cancer is a group of diseases characterized by uncontrolled and abnormal cell growth, leading to serious health consequences. Although various approaches are available for treating cancer, including chemotherapy, surgery, radiation, and immunotherapy, the severe adverse effects of these approaches limit their clinical effectiveness. New cancer treatment strategies including phototherapy uses light to treat cancer, which has attracted wide interest in the oncology research community. There are two types of phototherapy: photodynamic therapy (PDT) and phototherapy (PTT). PDT requires the administration of a photosensitizing agent and light exposure at a particular wavelength. On the other hand, PTT uses a photothermal agent that activates and kills cancer cells at a longer wavelength of light; hence, it is less energetic and, therefore, less harmful to other cells and tissues. PTT is gaining tremendous popularity because of its limited side-effects. A significant downside of PDT is that the photosensitizing drug stays in the body for a long time, which renders the patients extremely sensitive to light exposure. PDT is useful for the treatment of lining organs as they are can be easily reached by the light source. Although PDT is helpful for treating lining organs, its potential side-effects have been reported in the treatment of skin mouth esophagus and lung cancer, among others. Therefore, PTT remains a good alternative for cancer treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease and caused by various strains of mycobacteria. In the present study, pharmacophore model was developed using single ligand by ligand-based drug discovery approach. The key features responsible for DprE1 inhibitory activity were taken into consideration for developing pharmacophore. After the virtual screening, top 1000 hits were further subjected to docking study using GLIDE module, Schrödinger. Docking studies have shown promising interaction with amino residues with better glide score. Ligand-based drug design approach yielded a series of 15, 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide derivatives. All synthesized derivatives were characterized using NMR, mass, CHN analysis. The synthesized compounds were screened for In vitro antitubercular activity against Mycobacterium tuberculosis (H37Rv). Four compounds, 5g (MIC-1.01 μM); 5i (MIC-0.91 μM); 5k (MIC-0.82 μM); and 5o (MIC-1.04 μM) has shown promising activity compared to MIC of standard isoniazid (INH) and DprE1 enzyme inhibition was compared to BTZ043. Two halogen-substituted compounds have exhibited drastic enzyme inhibition. [ABSTRACT FROM AUTHOR]

Dasatinib which is available in market as a brand name of Sprycel tablets. Method was validated according to the ICH guidelines. The HPTLC method was developed using Camag HPTLC system. Silica G60 F254 precoated TLC plates were used as stationary phase. Mobile phase was used toluene: methanol (6:4). Dasatinib analysis was carried out in the absorbance mode at 240 nm. The drugs were satisfactorily show peak with RF 0.65 ± 0.03 for Dasatinib. Development method was validated as per ICH guideline using validation parameter like specification, linearity, accuracy, LOD, LOQ, precision, and robustness. The method was found to be linear in the range of 200ng-1.2µg and correlation coefficient value 0.997.dasatinib. In stability testing, Dasatinib were found susceptible to alkaline degradation. Because the method could effectively separate the drugs from their degradation products, it can be used as a stability indicating method. Degradation product of Dasatinib in alkaline condition was carried out and its degradation product is successfully separated and isolated by HPTLC method. Degradation product was identified by using MS-MS technique. [ABSTRACT FROM AUTHOR]

Analytical quality by design and the use of dissimilar chromatographic systems can be employed to accelerate chromatographic separations. Herein, a software (S-Matrix)-assisted platform was used to proficiently screen, optimize and select the optimal parameters for the chromatographic separation of ketoconazole and its related impurities. This approach evaluated the various chromatographic parameters in a stepwise manner based on the statistical tools and provided an in-depth understanding of the critical parameters influencing the peak selectivities and separations. It was demonstrated that dissimilar conditions, such as different stationary phases, mobile phase pH and organic modifiers (i.e. critical method variables), can improve the peak resolution, while the critical quality attributes can provide conditions appropriate for quantification purposes via a quality target analytical method. Furthermore, an orthogonal method was established to support the primary method. The orthogonality between the two methods was defined by the correlation matrix between the two systems using the Pearson correlation coefficient and was found to be 0.12. Using the optimized method, the primary method was validated as per International Council for Harmonization in the range of 0.05–1.0% for impurities and 80.0–120.0% for ketoconazole, thereby indicating the suitability of the method for use in quality control laboratories. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the present investigation was to separate, identify and characterize the major degradation products (DPs) of nelfinavir mesylate generated under hydrolytic, oxidative, photolytic and thermal stress conditions as advised in International Conference on Harmonization (ICH) guideline Q1A(R2). The drug was found to degrade under acidic, basic, oxidative and photolytic stress, while it was stable in neutral and thermal stress conditions. A total of three degradation products were formed, which were separated on a C-18 column employing a gradient HPLC method. A complete mass fragmentation pathway of the drug was first established with the help of multi-stage (MS n ) and MS/TOF accurate mass studies. Then stressed samples were subjected to LC–MS/TOF studies, which provided their fragmentation pattern and accurate masses. The mass spectral data were employed to characterize the DPs and assign structures to them. The total information was also used to establish the degradation pathway of the drug. The degradation products were identified as 3-hydroxy-N-((2R,3R)-3-hydroxy-1-(phenylthio)butan-2-yl)-2-methylbenzamide and (3S,4aS,8aS)-N-tert-butyl-2-((2R,3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzamido)-4-(phenylsulfinyl)butyl)decahydroisoquinoline-3-carboxamide. [Copyright &y& Elsevier]

A series of N′-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 11–66 and N′-[(2Z)-3-(4-bromophenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide 68–74 were synthesized using appropriate synthetic route. The entire test compounds 11–66 and 68–74 were assayed in vitro for antibacterial activity against two different strains of Gram-negative (E. coli and S. typhi), Gram-positive (S. aureus and B. subtilis) bacteria and the antimycobacterial activity was evaluated against H37Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial and antimycobacterial activity against the microbial strains used, when tested in vitro. In general, pyrazine ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 11, 12 and 40 were found to be most potent. The toxicity of most potent compounds 11, 12 and 40 were determined using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. The test compounds were found to be nontoxic up to a dose level of 250 μg/mL. [Copyright &y& Elsevier]

In a search of new potentially active antitubercular agents, here we have initiated with pharmacophore development, virtual screening and molecular docking studies to know flexible binding modes with target cavity of DprE1 enzyme. We have designed and synthesized 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives and evaluated for antitubercular activity with specific DprE1 inhibition. The various steps have been completed by performing condensation of 6-(trifluoromethyl)quinazoline-2-carboxylic acid, aromatic aldehydes, methanol, Hydrazine hydrate, -(trifluoromethyl)quinazoline-2-carbohydrazide, 6-(trifluoromethyl)-N′-methylenequinazoline-2-carbohydrazide to obtained 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives (3a–r) in better yields. Synthesized derivatives were characterized for their spectral analysis. These compounds have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 RV. The compounds 3a (MIC-1.27 μM); 3e (MIC-1.12 μM); 3p (MIC-1.18 μM); and 3r (MIC-0.96 μM); exhibited notable in vitro antitubercular activity compare to the reference standard, Isoniazid. These four compounds were screened for DprE1 enzyme assay. Among those 3e and 3r has shown strong DprE1 inhibition, these compounds were substituted with nitro and hydroxyl group. Image 1 • As per WHO report, tuberculosis (TB) is one of the leading cause of death in infectious disease across the globe. • Molecular modeling approach yielded 18 new quinazoline-2-carboxamide derivatives. • Newly synthesized derivatives studied for In vitro antitubercular activity. • Four compounds have shown better DprE1 Inhibitory Activity. [ABSTRACT FROM AUTHOR]

Tuberculosis has proved harmful to the entire history of mankind from past several decades. Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1) is a recent target which was identified in 2009 but unfortunately it is neither explored nor crossed phase II. In past several decades few targets were identified for effective antitubercular drug discovery. Resistance is the major problem for effective antitubercular drug discovery. Arabinose is constituent of mycobacterium cell wall. Biosynthesis of arabinose is FAD dependant two step epimerisation reaction which is catalysed by DprE1 and DprE2 flavoprotein enzymes. The current review is mainly emphases on DprE1 as a perspective challenge for further research. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the deadly cancers with very limited options of treatment and lack of new drugs. Cisplatin, doxorubicin and thiotepa are the drugs mostly used in therapy. Nine new N-cycloheptyl-substituted- 2,3-dihydro-1,3- benzothiazole-2-carboxamide derivatives were designed using structure based drug discovery. The designed compounds were docked to ascertain their binding against balder cancer cell lines (PDB code 3ERT). structure. The designed compounds were synthesised and characterized using different spectroscopic techniques. These novel compounds were evaluated on the MTT assay for there in vitro efficiency using the TCP1020 cell lines. The compounds 4e and 4i shown good inhibition. Two compounds of the series exhibit promising results which are in agreement with the in silico studies. The most potent compound against TCP1020 cell lines was compound 4i; IC50 = 7.8 μM. The activity of the 4i will be due to the inhibition of estrogenic binding receptor. [ABSTRACT FROM AUTHOR]

The last twenty years have seen noteworthy success in efforts to control HAT (Human African Trypanosomiasis) in Africa. HAT is a neglected tropical disease with major public health and economic effects in sub-Saharan Africa, and its effects on livestock productivity and development are considered major constraints to alleviating poverty in this region. The identification of important chemical features using the existing molecules will be helpful to discover the potent candidate to treat HAT. The development of novel HAT inhibitors is done using pharmacophore based virtual screening and docking study. The 3DQSAR was also performed to determine the predicted biological activity. The best hypothesis from PHASE, gave the five point pharmacophore hypothesis, AAPRR.687 with two hydrogen bond acceptors (A), two aromatic rings (R) and one charged group (P). Amongst them the pharmacophore hypothesis yielded a statistically significant 3D-QSAR model with 0.9521 as coefficient of determination (r2), a Pearson coefficient of 0.8796 and good F value and was considered to be the best pharmacophore hypothesis. The developed pharmacophore based 3D-QSAR model was validated by predicting the activity of test set molecules. The squared predictive correlation coefficient (q2) of 0.7359 was observed between experimental and predicted activity values of test set molecules. The developed pharmacophore was used to screen the chemical database. Subsequently the screened compounds were filtered by molecular docking. Finally five compounds were obtained as novel lead against human African trypanosomiasis. [ABSTRACT FROM AUTHOR]

The resistant to multidrug-resistant mycobacterium tuberculosis (MDR) strains has affected to the control on tuberculosis (TB). Drugs such as isoniazid and rifampin are commonly used for the therapy in TB. In these, in the phenomenon of the production of anti-TB drugs, the maintenance of the records is one of the challenging steps. The estimated global incidences of nearly half million are witnesses for MDR/rifampicin-resistant TB. This article included the global problem of the drug resistant to TB with its lengthy, complicated, and life-threatening effects with its poor results. Recently new medicines have been developed after a long time on the treatment of TB in MDR resistance. Levofloxacin, moxifloxacin, bedaquiline, delamanid, linezolid, and other second-line medications for TB treatment include levofloxacin, moxifloxacin, bedaquiline, delamanid, linezolid, and others. In the case of MDR-TB, a variety of medications are advised. In the treatment of TB, these medications are effective anti-TB drugs. The goal of this study is to analyze MDR-TB treatment methods in light of WHO guidelines for MDR-TB care in 2021. [ABSTRACT FROM AUTHOR]

• Potent E. coli DNA gyrase inhibitors obtained. • Compound 11b (IC 50 = 0.28 µM), 17b (IC 50 = 0.43 µM), 11a (IC 50 = 0.90 µM) and 17a (IC 50 = 0.72 µM) exhibited excellent E. coli DNA gyrase inhibitory activity. • Compounds 11b (MIC = 1.56 µg/ mL) and 17b (MIC = 3.125 µg/ mL) displayed encouraging anti-tubercular activity against M. tuberculosis H 37 Rv. • Compound 11b establishes good physicochemical properties and in vitro safety profiles. • Molecular docking studies were analysed. Bacterial DNA gyrase remains a prominent and vital target in discovering new antibacterial drugs. In the present research work, we designed and synthesized a series of novel 4,5-dibromo-N-phenyl-1H-pyrrole-2-carboxamide hybrids containing substituted 1,2,3-triazole and isoxazole moieties which could serve as potential E. coli DNA gyrase inhibitors. The title compounds were synthesized with a good to excellent yield, and all the newly synthesized compounds were characterized by physicochemical and spectral analysis (FTIR, 1H NMR, and 13C NMR). The DNA gyrase (E. coli) inhibitory assay was performed for all synthesized compounds. Results showed that four compounds, 11a (IC 50 = 0.90 µM), 11b (IC 50 = 0.28 µM), 17a (IC 50 = 0.72 µM) and 17b (IC 50 = 0.43 µM), exhibited good DNA gyrase inhibitory activity. In-silico molecular docking study was performed to understand the mode of interaction of compounds with the target enzyme. A docking study on the E. coli DNA gyrase protein revealed that compounds 11b (-7.011 kcal/mol) and 17b (-6.60 kcal/mol) interact with ARG136 and ASP73, two key amino acid residues, with docking scores of −7.01 and −6.60, respectively. The MD simulation was further employed to elucidate the thermodynamic binding energy, RMSD, and RMSF of compounds 11b and 17b. They exhibited binding energies of -47.598 kcal/mol and -41.682 kcal/mol, respectively. This provides valuable information on the binding mode and structure-activity relationship of these new hybrids of 4,5-dibromo-N-phenyl-1H-pyrrole-2-carboxamides as promising E. coli DNA gyrase B inhibitors. In addition, these hybrid derivatives showed more prominent antibacterial action on Gram-negative rather than Gram-positive organisms. Surprisingly, compounds 11b (MIC = 1.56 µg/mL) and 17b (MIC = 3.125 µg/mL) also displayed promising anti-mycobacterial activity. [Display omitted] [ABSTRACT FROM AUTHOR]

• SFC and NP-LC technique is used to separate itraconazole stereoisomers. • We developed a rapid and green method for the separation of itraconazole stereoisomers. • This platform will aid in the Quality control Laboratories to adapt Eco-friendly method. Separation of the stereoisomers of the antifungal drug itraconazole using supercritical fluid chromatography and normal-phase liquid chromatography is presented. The performances of the two methods are evaluated based on their speed, resolution, and the analytical method greenness score. Both methods achieve baseline separation and meet the United States Pharmacopeia-recommended resolution of ≥1.5 between the four stereoisomers. The methods are validated following the International Conference on Harmonization guidelines and evaluated in terms of specificity, precision, linearity, accuracy, and range; they are thus appropriate for purposes of quantification. Supercritical fluid chromatography achieves separation more rapidly and is found to be more eco-friendly than normal-phase liquid chromatography. To emphasize the use of ecofriendly alternatives, the assessment is performed using a metric termed as the analytical method greenness score. The method can thus be implemented for determination of chiral purity in various Quality control laboratories. [ABSTRACT FROM AUTHOR]

In recent years, design and synthesis of anticonvulsants effective against multiple seizures has attracted much attention of medicinal chemists. In an attempt to find novel anticonvulsants, herein we have reported structurally optimized sixteen different substituted quinazolinones explored through molecular fragmentation approach. The anticonvulsant activity of synthesized compounds was assessed by using predictable seizure models in mice. Two most promising analogues 8 d (ED50 = 35.1 mg/kg, MES, mice, i. p.; ED50 = 41.5 mg/kg, scPTZ test, mice, i. p.) and 8 l (ED50 = 21.2 mg/kg, MES, mice, i. p.; ED50 = 32.4 mg/kg, scPTZ test, mice, i. p.) exhibited broad spectrum anticonvulsant action in preclinical models of seizures. Compound 8 l was also shown profound activity against pharmaco‐resistant limbic seizures produced in 6 Hz test. Most of the synthesized molecules exhibited moderate to high anticonvulsant activity in all seizure models with no symptoms of neurotoxicity and hepatotoxicity. We have also used in‐silico protocol for prediction of physiochemical and pharmacokinetic properties of synthesized quinazolinones. The promising anticonvulsant activity of synthesized analogues, ex‐vivo toxicity, in‐silico molecular docking, physiochemical and pharmacokinetic predictions make us to anticipate emergence of synthesized quinazolinones as valid leads for the treatment of convulsive disorder. [ABSTRACT FROM AUTHOR]