Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

Separation of hematite from banded hematite jasper (BHJ) by magnetic coating

The separation of iron oxide from banded hematite jasper(BHJ) assaying 47.8% Fe, 25.6% Si O2 and 2.30%Al2O3 using selective magnetic coating was studied. Characterization studies of the low grade ore indicate that besides hematite and goethite,jasper, a microcrystalline form of quartzite, is the major impurity associated with this ore. Beneficiation by conventional magnetic separation technique could yield a magnetic concentrate containing 60.8% Fe with 51% Fe recovery. In order to enhance the recovery of the iron oxide minerals, fine magnetite, colloidal magnetite and oleate colloidal magnetite were used as the coating material. When subjected to magnetic separation, the coated ore produces an iron concentrate containing 60.2% Fe with an enhanced recovery of56%. The AFM studies indicate that the coagulation of hematite particles with the oleate colloidal magnetite facilitates the higher recovery of iron particles from the low grade BHJ iron ore under appropriate conditions.     

Investigation on external stimuli engendered magnetic ordering in polycrystalline CaCu3Ti4O12 quadruple perovskite

The consequences of high energy mechanical milling, microwave-assisted heating and rapid thermal cooling on magnetic ordering in polycrystalline CaCu₃Ti₄O₁₂ cubic perovskite have been investigated by means of X-ray powder diffractometry (300?K), dc magnetization in field – cooled and zero – field cooled modes (H = 100?Oe and 1000?Oe, T?=?5–300?K) (M – T curves) and M – H loop characteristics (T?=?5?K and 300?K, H_max = 70?kOe). The M – T curves of unmilled and 16?h milled samples show pure antiferromagnetic and weak ferromagnetic ordering, respectively, 1?h and 6?h milled samples demonstrate the coexistence of both the phases while microwave-assisted and quenched samples exhibit classic antiferromagnetic transition and a low temperature paramagnetic–like contribution with different weights, well supported by the M – H loop characteristics. The observed transformations in the magnetic ordering are attributed to the ball-milling induced stress which curtails hybridization of empty Ti-3d orbitals with Cu-3d and O-2p orbitals and secondary phase formation. Oxygen vacancies associated with bound magnetic polarons originate ferromagnetism in the milled samples while unpaired electrons inhabited at the empty sites are the cause of paramagnetic centers. The low-temperature Curie – tail in M – T curve for quenched and microwave assisted samples is attributed to Ti³⁺ cations.     

Lecture capture with real‐time rearrangement of visual elements: impact on student performance

The primary goal of this study is to create and test a lecture‐capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the instructor and students' images, into lecture videos that are embedded in a website for students to review after school. The present study employed a two‐group experimental design, with 153 participants (145 females and 8 males) making up an experimental group in which lecture courses were recorded using the new lecture‐capture system, and 149 participants (140 females and 9 males) forming a control group whose lectures were recorded by traditional means. All participants were in the freshman college and studying Introduction to Computer and Information Science in one of six classes, and were randomly assigned to one of the two groups. The participants' midterm examination and final examination scores were collected as indicators of their academic performance, with their mathematics entrance scores used as a pre‐test. The findings obtained from analysis of covariance (ANCOVA) suggest that appropriate rearrangement of visual elements in lecture videos can significantly impact students' learning performance.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.