Search

Herein, we present a new library of 3-(2-(pyrimidin-5-yl)thiazol-4-yl)-1,2,4-oxadiazole (14a–j) as an anticancer agent designed based on in silico fragment-based drug design (FBDD). The derivatives were synthesized and characterized by 1HNMR,13CNMR, HRMS, and FT-IR. The library was named "pyrimidine-thiazole-1,2,4-oxadiazoles." In addition, the MTT assay was used to test the compounds (14a–j) for their potential anticancer activity in a panel of four human cancer cell lines, such as PC3 & DU-145 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer), and the normal Vero cell lines, using the widely used anticancer drug etoposide acting as a reference drug and positive control. The value obtained was presented as IC50 (µM). The IC50 values of the reference standard ranged from 1.97 ± 0.45 µM to 3.08 ± 0.135 µM, while the library of tested compounds showed IC50 values ranging from 0.02 ± 0.0031 µM to 10.3 ± 6.25 µM. Among the tested compounds, six of them showed promising anticancer activity: 14a, 14b, 14c, 14d, 14e and 14j. Especially, one compound, 14a, showed excellent anticancer activity in all the tested cell lines. All compounds showed selective cytotoxicity against cancer cells but not against normal Vero cells (IC50 = >19 µM), justifying the designing approach to develop a selective anticancer agent. These compounds were also subjected to docking experiments to investigate potential binding site interactions, and the results were consistent with the in vitro results. [ABSTRACT FROM AUTHOR]

Plant-derived nanoparticles have multi-functionalities owing to their ecological origin and biocompatible nature. A novel and stable silver nanoparticle (AgNP) was reported here using Cyanthillium cinereum (C. cinereum) as a reducing as well as capping agent by rapid microwave-assisted green method. The synthesized nanoparticles revealed their crystalline and spherical nature with an average size of 19.25 ± 0.44 nm in HR-TEM analysis. The excitation of electrons from occupied d-bands to states above the Fermi level while employing photoluminescence studies of AgNP indicated their awesome optical properties. Rapid decomposition of dangerous organic dyes like methylene blue and fuchsine in the catalytic presence of AgNP was evidenced from simple UV–visible spectral analysis. In vitro antioxidant potential assessed by DPPH assay indicated an IC50 value of 40.80 ± 0.14 μg/mL for the new AgNP. A substantial control on the growth of pathogenic bacteria such as Staphylococcus aureus and Klebsiella pneumonia can be achieved by synthesized nanoparticles as demonstrated by the well diffusion method. AgNP was also functioned as a non-enzymatic electrochemical sensor with a sharp oxidation peak with peak potentials at 0.366 V and it has a wide application as a bio sensor in neurobiology especially in the detection of neurotransmitters like dopamine with high sensitivity. [ABSTRACT FROM AUTHOR]

Screening experiments were done using 21 different commercially available ketoreductase enzymes (10 mg), substrate B 9 b (5 mg in 100 µl isopropanol) and 900 µl phosphate buffer having pH 7.0 at a temperature 25-30 °C. Further, to optimize enzyme load, two reactions were carried out using 10% and 1% CDX-021 enzyme with respect to substrate B 9 b . Both the reactions showed the same conversion using 30% isopropyl alcohol (IPA) and 70% phosphate buffer having pH 7.0 at temperature 28-30 °C. [Extracted from the article]

An improved process for the synthesis of latanoprost having excellent optical purity (de 99.9%, [α]D20 = +35.37° (c = 0.90, acetonitrile)) without use of preparative HPLC is described. This process involves effective purification of hydroxyl intermediate (5A) through solvent crystallization followed by inhibition of inversion of the chiral center at C-15 position. This was possible due to judicious use of diol intermediate (6) for double bond reduction prior to hydroxyl protection. [ABSTRACT FROM AUTHOR]

Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition. [ABSTRACT FROM AUTHOR]

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier. Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed forin vitrorelease kinetics,ex vivopermeation andin situnasal perfusion. Cytotoxic potential of CPCsin vitrowas evaluated on LN229 human glioblastoma cells. Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21.In vitrodrug release showed initial burst release followed by slow and continues release indicating biphasic pattern. Theex vivopermeation pattern through sheep nasal mucosa also exhibited a similar release pattern as forin vitrorelease studies.In situnasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution.In vitrocytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery. [ABSTRACT FROM AUTHOR]

In the last half-century, filmmaker Frederick Wiseman (b. 1930) has produced an incomparable series of documentaries which collectively comprise a study of institutions. Two of these, Model (1980) and The Store (1983), concern fashion. This paper provides context for understanding these two movies within Wiseman's iconoclastic oeuvre, including an interview with the artist himself. [ABSTRACT FROM AUTHOR]

Cisplatin is an anticancer drug extensively used against a variety of cancers. Cisplatin chemotherapy is found to manifest dose-dependent nephrotoxicity. Depletion of the renal antioxidant defence system has been suggested to be the main cause of cisplatin-induced nephrotoxicity. The purpose of this study is to investigate whether the ethanol extract of entire plant of Sphaeranthus indicus could reduce the intensity of toxicity in albino rats. Nephrotoxicity was assessed by determining the serum creatinine and urea levels and renal antioxidant status in rats after cisplatin administration (12 mg kg−1 body weight, i.p.). The ethanol extract of S. indicus (150 and 300 mg kg−1 body weight) was administered orally from the sixth day onwards for 10 days after cisplatin administration. The extract significantly reduced the elevated serum creatinine and urea levels. Renal antioxidant defence systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione level that are depleted by cisplatin therapy were restored to normal by treatment with the extract. Cisplatin-induced lipid peroxidation was also found to be markedly reduced by treatment with the extract. These results suggest that S. indicus has protective effect against cisplatin-induced nephrotoxicity, which may be attributed to its antioxidant potential. [ABSTRACT FROM PUBLISHER]

Presents the short story "What Grown-Ups Know," by Alex Joseph.