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We herein report the design and synthesis of new 1,3,5-triazine-based pyrazole derivatives (5a–i) with anticancer activity targeting the epidermal growth factor (EGFR) tyrosine kinase. The newly synthesized compounds were characterized using spectroscopic techniques such as 1H NMR, 13C NMR, mass spectrometry and elemental analysis. All the compounds exhibited moderate to good anticancer activity against MCF-7 (human breast), HepG2 (human liver), HCT116 (human colorectal), PC-3 (human prostate), LoVo (human colon) and LoVo/DX (doxorubicin-resistant) cancer cell lines except compound 5i, which exhibited poor activity. Compounds 5f, 5g and 5h possessed more promising anticancer activity and the results were expressed as IC50 values in nM. These compounds also displayed potent inhibitory activity against EGFR-tyrosine kinase with IC50 values of 395.1, 286.9 and 229.4 nM, respectively in comparison with the standard drug, erlotinib. The docking studies revealed that the compounds showed a good affinity towards the target EGFR kinase (PDB ID: 6V6O) by forming multiple H-bonds with amino acids. The binding interaction of the more active compounds (5f, 5g and 5h) with Ct-DNA was explored using spectroscopic, viscometric, electrochemical and docking techniques. Both the experimental and theoretical findings of DNA binding showed consistent results and confirmed the groove mode of interaction of these compounds with DNA. The in vitro ADME properties were also evaluated, thus allowing the identification of optimized compounds as promising anticancer agents. Finally, density functional theory (DFT) geometry optimization and the relevant quantum parameters were calculated for the active compounds using the B3LYP level. [ABSTRACT FROM AUTHOR]

A series of 2,3-disubstituted quinazolin-4(1H)-ones (3a–j) were screened for their antimicrobial activity via the minimum inhibitory concentration method (MIC). The in vitro anti-tubercular (TB) activity of compounds against Mycobacterium tuberculosis (Mtb) H37Rv was evaluated. Among the screened compounds, 3g and 3h exhibited more potent anti-TB activity with MIC values of 2.15 and 0.75 μM, respectively. The compound 3g and 3h were tested for cytotoxic activity against the mammalian Vero cell line. Docking studies were performed on the enoyl acyl carrier protein (InhA) to understand the mechanism of actions of the compounds. The study revealed that the compounds have a strong anti-TB activity and showed a good affinity toward the protein. Hence, the target compounds 3g and 3h can be adapted and produced more effectively as lead compounds in the treatment of multi-drug resistant tuberculosis. Furthermore, the interaction of lead compounds 3g and 3h with DNA was studied by UV-Visible, fluorescence, and circular dichroism (CD) spectroscopy, cyclic voltammetry (CV) and dynamic viscosity measurements. The studies showed that the groove binding mode of interaction is predominant between DNA and compounds (3g and 3h). The viscosity and absorption results obtained for compound 3g indicated that the Ct-DNA binding properties were enhanced as compared to compound 3h with Kb values of 8.58 × 104 and 3.41 × 104 L Mol−1, respectively. The B3LYP level of density functional theory (DFT) was used to obtain ground state geometries, molecular electrostatic potential (MEP) surfaces, and HOMO–LUMO energy calculations. [ABSTRACT FROM AUTHOR]

A novel class of 3‐(4‐chlorophenyl)‐2‐(substituted)quinazolin‐4(3H)‐one derivatives were synthesized, and the structure of synthesized compounds was characterized by IR, 1H NMR, and mass spectroscopy. The newly synthesized compounds (4a–g and 6a–g) were tested for their in vitro cyclooxygenase (COX) inhibition activity. The compounds have inhibitory profile against both COX‐1 and COX‐2, and some of the compounds are found to be selective against COX‐2. The compound 6g showed distinct inhibitory activity on COXs. The synthesized compounds were evaluated for their potential anti‐inflammatory activity as inhibitors of the proinflammatory cytokines IL‐6. Compounds 4d–g showed the highest level of inhibition among all the tested compounds. Thus, our data suggested that these compounds may represent a new class of potent anti‐inflammatory agents. [ABSTRACT FROM AUTHOR]

Polyaniline-few-layer molybdenum disulfide nanocomposite (PANI-MoS2) has been synthesized by in situ polymerization of aniline over MoS2 using HCl as the dopant. X-ray crystallographic studies show the characteristic peaks of few-layered MoS2 in the PANI matrix. The changes in Raman and UV-Vis spectra have proved that there are definite interactions between PANI and few-layer MoS2.PANI-MoS2 nanocomposite as an electrode material for supercapacitor exhibits a maximum specific capacitance of 687 Fg−1 at a scan rate of 5 mVs−1 using cyclic voltammetry (CV) and a Csp of 612 Fg−1 at a current density of 0.2 Ag−1 using chronopotentiometry (CP). Further, the material also exhibits a high energy density of 128 Wh kg−1with a maximum power density of 9.8 kW kg−1 and a tremendous cyclic stability with 93% capacitance retention after 2000 cycles. These superior electrochemical results over bare PANI and MoS2 showed the PANI-MoS2 nanocomposites to be a capable electrode material for energy storage systems. [ABSTRACT FROM AUTHOR]

Contemporary research reveals an undemanding protocol for the catalytic synthesis of 1,2,4-oxadiazole-quinolinepeptide in the incidence of a cost-effective and reusable mesoporous ZrO2-supported Cu2O (Cu2ZrO3) catalyst. This paper depicts a unique system for peptide bond synthesis staying away from toxic solvents and reactants. The catalyst was reused for four cycles without noteworthy loss in the activity, and the catalyst was genuinely heterogeneous. The method followed a simple workup procedure, and no column chromatography was needed. Further, the synthesized 1,2,4-oxadiazole-quinolinepeptide ligand (L), and its complexes of type, [FeLCl2] and [CuL]Cl2 were synthesized and characterized by spectral and analytical techniques. An octahedral geometry has been projected for Fe(II) complexes, while the Cu(II) complex exhibits a square planar geometry. The binding properties of the complexes with CT-DNA were studied by absorption spectral analysis, followed by viscosity measurement and thermal denaturation studies. The photo-induced cleavage studies revealed that the complexes possess photonuclease activity against pUC19 DNA under UV–visible irradiation. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcer is one of the most feared complications of diabetes and is associated with more morbidity. Diabetes patients have a life-time risk as high as 25% for developing foot ulceration and it is the most common cause of non-traumatic amputation. Objectives: This study was undertaken to determine the clinical characteristics, risk factors, bacteriology, and outcome of diabetic foot ulcer. Materials and Methods: A prospective study was conducted from April 2012-March 2013 in endocrinology department of Gauhati Medical College, Assam. Forty cases of diabetic foot ulcer patients underwent detailed history, clinical examination, laboratory examination including microbiological culture and sensitivity. Results: Among 40 cases, 31 were males (77.5%) and 9 (22.5%) were females. The mean age of cases was 55.2 ± 10.2 years. The mean duration of diabetes was 7.2 ± 5.5 years. Most of the cases had poor glycemic control (mean HbA1 c 10.6% ±2.5). Most of our cases had Wagner's grade II ulcer (72.5%), grade III (17.5%) and grade IV (10%). The most common risk factors for diabetic foot ulcers were lack of foot care knowledge (82.5%), peripheral neuropathy (77.5%), hypertension (60%), and smoking (52.5%). Out of 40 cases, 67.5% had monomicrobial infection, 27.5% had polymicrobial infection and 8% were culture negative. In our study, gram positive (57.6%) bacterial infections were predominant than gram negative (42.8%); among which Staphylococcus aureus was the common bacteria isolated. Six (15%) patients who underwent amputation had grade III and IV ulcer along with polymicrobial infection. Conclusions: In our study, most common risk factors for diabetic foot ulcer were lack of foot care knowledge, peripheral neuropathy, hypertension, and spontaneous blisters. Cases with higher grade of ulcer had longer hospital stay and high risk of amputation. Hence, providing proper foot care education, good glycemic control, early and aggressive management of diabetic foot ulcer will reduce the morbidity associated with diabetic foot ulcer. [ABSTRACT FROM AUTHOR]

Based on the reduction of permanganate by sumatriptan succinate (STS) in acidic medium, two simple, sensitive and cost-effective methods were described for the determination of STS in bulk drug and in formulation. In titrimetry (method A), STS was oxidized by a known excess of potassium permanganate (KMnO4) in H2SO4 medium followed by determination of unreacted permanganate by titration with ferrous ammonium sulphate. In spectrophotometry (method B), STS was treated with a measured excess of permanganate in acid medium and the unreacted oxidant was measured at 545 nm. The molar combining ratio in titrimetry and the optimum assay conditions were studied. Titrimetry was applicable over 1-7 mg range and the calculations were based on a 1:6 (STS: KMnO4) molar ratio. In spectrophotometry, Beer's law was obeyed over 0.8-16.0 μg ml-1 concentration range of STS. The molar absorptivity and Sandell sensitivity values are calculated to be 1.39 × 104 ∣ mol-1 cm-1 and 0.03 μg cm-2, respectively. The limits of detection (LOD) and quantification (LOQ) were also reported for the spectrophotometric method. The applicability of the developed methods was demonstrated by the determination of STS in pure drug as well as in commercial dosage form. [ABSTRACT FROM AUTHOR]

Two simple, selective, and rapid spectrophotometric methods are described for the determination of mycophenolate mofetil (MPM) in pure form and in tablets. Both methods are based on charge-transfer complexation reaction of MPM with p-chloranilic acid (p-CA) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in dioxane-acetonitrile medium resulting in coloured product measurable at 520 nm (p-CA) or 580nm (DDQ). Beer's law is obeyed over the concentration ranges of 40-400 and 12-120 µgmL-1 MPM for p-CA and DDQ, respectively, with correlation coefficients (r) of 0.9995 and 0.9947. The apparent molar absorptivity values are calculated to be 1.06 × 10³ and 3.87 × 10³ Lmol-1 cm-1, respectively, and the corresponding Sandell's sensitivities are 0.4106 and 0.1119 µg cm-1. The limits of detection (LOD) and quantification (LOQ) are also reported for both methods. The described methods were successfully applied to the determination of MPM in tablets. Statistical comparison of the results with those of the reference method showed excellent agreement. No interference was observed from the common excipients present in tablets. Both methods were validated statistically for accuracy and precision. The accuracy and reliability of the methods were further ascertained by recovery studies via standard addition procedure. [ABSTRACT FROM AUTHOR]

Detection of anticancer drug (doxorubicin) using an electrochemical sensor is developed based on a transition metal vanadate's related carbon composite material. With an environmentally friendly process, we have synthesized a metal oxide composite of iron vanadate nanoparticle assembled with sulfur-doped carbon nanofiber (FeV/SCNF). The FeV/SCNF composite was characterized using XRD, TEM, FESEM with elemental mapping, XPS and EDS. In contrast to other electrodes reported in the literature, a much-improved electrochemical efficiency is shown by FeV/SCNF composite modified electrodes. Amperometric technique has been employed at 0.25 V (vs. Ag/AgCl) for the sensitive detection of DOX within a wide range of 20 nM–542.5 μM and it possesses enhanced selectivity in presence of common interferents. The modified electrochemical sensors show high sensitivity of 46.041 μA μM−1 cm−2. The newly developed sensor could be used for the determination of doxorubicin in both blood serum and drug formulations with acceptable results, suggesting its feasibility for real-time applications. [ABSTRACT FROM AUTHOR]