Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells.

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI and exerted a superior potency over the reference standard SP600125 against the tested cell lines.

Design and synthesis of new adamantyl derivatives as promising antiproliferative agents.

A series of adamantyl carboxamide derivatives containing sulfonate or sulfonamide moiety were designed as multitargeted inhibitors of ectonucleotide pyrophosphatases/phosphodiesterases (NPPs) and carbonic anhydrases (CAs). The target compounds were investigated for their antiproliferative activity against NCI-60 cancer cell lines panel. Three main series composed of 3- and 4-aminophenol, 4-aminoaniline, and 5-hydroxyindole scaffolds were designed based on a lead compound (A).

A New Combination of Radio-Frequency Coil Configurations Using High-Permittivity Materials and Inductively Coupled Structures for Ultrahigh-Field Magnetic Resonance Imaging.

In ultrahigh-field (UHF) magnetic resonance imaging (MRI) system, the RF power required to excite the nuclei of the target object increases. As the strength of the main magnetic field (B0 field) increases, the improvement of the RF transmit field (B1+ field) efficiency and receive field (B1- field) sensitivity of radio-frequency (RF) coils is essential to reduce their specific absorption rate and power deposition in UHF MRI. To address these problems, we previously proposed a method to simultaneously improve the B1+ field efficiency and B1- field sensitivity of 16-leg bandpass birdcage RF coils (BP-BC RF coils) by combining a multichannel wireless RF element (MCWE) and segmented cylindrical high-permittivity material (HPM) comprising 16 elements in 7.

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae.

is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs.

Potent Imidazothiazole-based Inhibitor of BRAF V600E Overcomes Acquired Resistance Inhibition of RAF Dimerization in PLX4032-resistant Melanoma.

Background/aim: The B-raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation is frequent in patients with advanced melanoma. PLX4032, an inhibitor of BRAFV600E kinase, is effective for the treatment of melanoma in BRAF V600E-positive patients; however, resistance eventually develops due to paradoxical activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway resulting from RAF dimerization. In this study, we investigated the inhibitory effects of a novel imidazothiazole-based compound, KS28, on RAF dimerization and resistance to PLX4032 in melanoma.

Structural optimization of 4-(imidazol-5-yl)pyridine derivatives affords broad-spectrum anticancer agents with selective B-RAF/p38α kinase inhibitory activity: Synthesis, in vitro assays and in silico study.

In the current article, we introduce design of a new series of 4-(imidazol-5-yl)pyridines with improved anticancer activity and selective B-RAF/p38α kinase inhibitory activity. Based on a previous work, a group of structural modifications were applied affording the new potential antiproliferative agents. Towards extensive biological assessment of the target compounds, an in vitro anticancer assay was conducted over NCI 60-cancer cell lines panel representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers.

Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE Productions and Nitric Oxide in Murine RAW 264.7 Macrophages.

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E (PGE) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds - have first been assessed for cytotoxicity against RAW 264.

Anticancer profile and anti-inflammatory effect of new N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives.

A new series of N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives 11a-o were designed and synthesized based on our previous works. The new series was tested for its anticancer and anti-inflammatory effects. The anticancer profile of final target compounds was obtained by testing them over 60 cell lines belong to nine types of cancers.

Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors.

This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. There are no other reported selective inhibitors of this kinase in the literature, that's why they are considered as first-in-class. In addition, none of the reported non-selective ErbB4 inhibitors possesses imidazothiazole nucleus in its structure.

Discovery of New Imidazo[2,1-]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising and Anti-melanoma Activity.

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types.

Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAF/p38α inhibitors.

The synergistic effect of dual inhibition of serine/threonine protein kinases that are involved in the same signalling pathway of the diseases can exert superior biological benefits for treatment of these diseases. In the present work, a new series of (imidazol-5-yl)pyrimidine was designed and synthesized as dual inhibitors of BRAF and p38α kinases which are considered as key regulators in mitogen-activated protein kinase (MAPK) signalling pathway. The target compounds were evaluated for dual kinase inhibitory activity.

Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor.

P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF imidazol-5-yl pyridine inhibitors to inhibit P38α kinase. A group 25 reported P38α kinase inhibitors were used to build a pharmacophore model for mapping the target compounds and proving their affinity for binding in P38α active site.

Design, synthesis, and biological evaluation of novel imidazole derivatives possessing terminal sulphonamides as potential BRAFinhibitors.

BRAF mutation has been detected in various malignant tumours. Developing of potent BRAF inhibitors is considered a leading step in the way to cure different cancer types. In the current work, a series of 38 4-(1H-imidazol-5-yl)pyridin-2-amine derivatives was designed and synthesized using Dabrafenib as a lead compound for structural-guided optimization.

Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies.

A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound is the most potent against both kinases with IC values 0.

Novel Imidazo[2,1-b]oxazole Derivatives Inhibit Epithelial Cell Transformation and Triple Negative Breast Cancer Tumorigenesis.

Background/aim: Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with limited targets for chemotherapy. This study evaluated the inhibitory effects of novel imidazo[2,1-b]oxazole-based rapidly accelerated fibrosarcoma (RAF) inhibitors, KIST0215-1 and KIST0215-2, on epithelial cell transformation and TNBC tumorigenesis.

Materials And Methods: Immunoblotting, BrdU incorporation assay, reporter gene assay, and soft agar assay analyses were performed.

Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular docking.

B-Raf mutation was identified as a key target in cancer treatment. Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against V600E B-Raf kinase.

Structural optimization of imidazothiazole derivatives affords a new promising series as B-Raf V600E inhibitors; synthesis, in vitro assay and in silico screening.

BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen new imidazo[2,1-b]thiazole derivatives with m-nitrophenyl group at position 6.

Design and synthesis of novel pyrrolo[2,3-b]pyridine derivatives targeting BRAF.

Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved B-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent B-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their B-RAF inhibitory effect at single dose (10 μM).

Synthesis, biological evaluation, and docking studies of new pyrazole-based thiourea and sulfonamide derivatives as inhibitors of nucleotide pyrophosphatase/phosphodiesterase.

A series of six compounds (1a-f) possessing pyridine-pyrazole-benzenethiourea or pyridine-pyrazole-benzenesulfonamide scaffold were synthesized. The target compounds were screened to evaluate their inhibitory effect on human nucleotide pyrophosphatase/phosphodiesterase 1 and -3 (ENPP1 and ENPP3) isoenzymes. Compounds 1c-e were the most potent inhibitors of ENPP1 with sub-micromolar IC values (0.

Antiproliferative activity of cycloalkanecarboxamide derivatives possessing sulfonate or sulfamate moiety.

A series of cycloalkanecarboxamide-containing sulfonate and sulfamate derivatives were prepared, and their antiproliferative activity was tested against NCI-60 cancer cell lines panel. Compound 1f possessing cyclohexyl and p-(tert-butyl)benzenesulfonate moieties was the most active among all the target compounds. It exerted broad-spectrum anticancer activity against all the nine cancer types involved in the NCI-60 panel.

Clinical application of cryolipolysis in Asian patients for subcutaneous fat reduction and body contouring.

Background: Cryolipolysis, a preferred method for minimally invasive body contouring, involves the noninvasive cooling of adipocytes to induce lipolysis without damaging other tissues. This study aimed to evaluate the safety and efficacy of cryolipolysis for the treatment of excessive fat tissue.

Methods: Between May 2014 and December 2017, 231 patients with 448 areas of interest were enrolled and their records were retrospectively reviewed.

All- Retinoic Acid Overcomes Acquired Resistance to PLX4032 Inhibition of PIN1 in Melanoma Cells.

Background/aim: PLX4032 is commonly used in the treatment of advanced melanoma patients with BRAF-V600E mutation. The aim of this study was to elucidate the mechanisms by which up-regulation of PIN1 confers PLX4032 resistance in melanoma.

Materials And Methods: The expression of PIN1 as well as the cytotoxic effects of combinatorial treatment of PLX4032 and all-trans retinoic acid (ATRA) were investigated by immunoblotting, MTT assay, TUNEL assay, and soft agar assay.

A Study on the Effective Ratio of Fat to Stromal Vascular Fraction for Cell-Assisted Lipotransfer.

Background: Fat grafting, used for soft tissue augmentation during aesthetic or reconstructive plastic surgery, has disadvantages of low efficiency and unpredictable resorption rate. As an alternative, cell-assisted lipotransfer (CAL) is widely used because of its simplicity and low fat resorption rate. However, relevant studies on optimal CAL parameters are still lacking.