Discovery of Substituted 2-oxoquinolinylthiazolidin-4-one Analogues as Potential EGFRK Inhibitors in Lung Cancer Treatment.

PURPOSE: Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer and the chemotherapeutic drugs available have high toxicity and have reported side effects hence, there is a need for the synthesis of novel drugs in the treatment of cancer. METHODS: The current research work dealt with the synthesis of a series of 3-(3-acetyl-2-oxoquinolin-1-(2H)-yl-2-(substitutedphenyl)thiazolidin-4-one (Va-j) derivatives and evaluation of their in-vitro anticancer activity. All the synthesized compounds were satisfactorily characterized by IR and NMR data. Compounds were further evaluated for their in-vitro anticancer activity against A-549 (lung cancer) cell lines. The in-vitro anticancer activity was based upon the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay method. RESULTS: The synthesized compounds exhibited satisfactory anticancer properties against the A-549 cell line. The compound (VH): showed the highest potency amongst the tested derivatives against the A-549 cell line with IC50 values of 100 µg/ml respectively and was also found to be more potent than Imatinib (150 µg/ml) which was used as a standard drug. Molecular docking studies of the titled compounds (Va-j) were carried out using AutoDock Vina/PyRx software. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the EGFRK tyrosine kinase domain (PDB 1m17). CONCLUSION: Among all the synthesized analogues, the binding affinity of the compound (Vh) was found to be higher than other synthesized derivatives and a molecular dynamics simulation study explored the stability of the docked complex system.

Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review.

Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.

Polymer Backbone Stabilized Methylammonium Lead Bromide Perovskite Nano Islands.

Organic-inorganic hybrid perovskite materials continue to attract significant interest due to their optoelectronic application. However, the degradation phenomenon associated with hybrid structures remains a challenging aspect of commercialization. To overcome the stability issue, we have assembled the methylammonium lead bromide nano islands (MNIs) on the backbone of poly-3-dodecyl-thiophene (PDT) for the first time. The structural and morphological properties of the MNI-PDT composite were confirmed with the aid of X-ray diffraction (XRD) studies, Field emission scanning electron microscope (FESEM), and X-ray photoelectron spectroscopy (XPS). The optical properties, namely absorption studies, were carried out by ultraviolet-visible spectroscopy. The fluorescent behavior is determined by photoluminescence (PL) spectroscopy. The emission peak for the MNI-PDT was observed at 536 nm. The morphology studies supported by FESEM indicated that the nano islands are completely covered on the surface of the polymer backbone, making the hybrid (MNI-PDT) stable under environmental conditions for three months. The interfacial interaction strategy developed in the present work will provide a new approach for the stabilization of hybrids for a longer time duration.

Mechanochemically interlocked cubane copper complex interface for WOLED.

In the rapid development of organic light-emitting diodes (OLEDs), phosphorescent transition metal complexes have played a crucial role as the most promising candidates for next generation display and lighting applications. However, most devices are fabricated using iridium and platinum-based complexes which are expensive and available in very limited quantities, whereas using relatively abundant organometallic complexes for fabrication results mostly in inefficient performance results. To overcome these issues, we have synthesized tetra copper iodide with tetra triphenyl cage like structure (denoted as CIPh) as an emerging class of luminescent material by mechanochemical grinding followed by thermal treatment for application in white OLED. The CIPh complex exhibits considerable quantum yield and a millisecond decay lifetime. Phosphorescent OLEDs were fabricated using CIPh complex as emitter shows a remarkable performance with external quantum efficiency and current efficiency of 5.28 % and 22.76 cd/A, with a high brightness of 4200 cd m-2, respectively. White OLEDs were also fabricated with a fluorescent blue and phosphorescent red emitted with (CIPh) as green emitter and achieved an impressive CRI of 82 with an EQE of over 3 %. This is the first ever attempt at fabricating WOLEDs using organocopper complex.