Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and Studies.

The new dibenzoazepine-substituted triazole hybrids (-) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. The hybrid structures (-) were obtained in high yields (74-98%) with a simple two-step synthesis strategy and fully characterized. These compounds were assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE).

Novel benzothiazole/benzothiazole thiazolidine-2,4-dione derivatives as potential FOXM1 inhibitors: In silico, synthesis, and in vitro studies.

The oncogenic transcription factor FOXM1 overexpressed in breast and other solid cancers, is a key driver of tumor growth and progression through complex interactions, making it an attractive molecular target for the development of targeted therapies. Despite the availability of small-molecule inhibitors, their limited specificity, potency, and efficacy hinder clinical translation. To identify effective FOXM1 inhibitors, we synthesized novel benzothiazole derivatives (KC10-KC13) and benzothiazole hybrids with thiazolidine-2,4-dione (KC21-KC36).

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells.

FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases.

Discovery of potential RSK1 inhibitors for cancer therapy using virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA calculations.

The p90 ribosomal protein S6 Kinase (RSK) family belongs to Ser/Thr protein kinases that includes four isoform RSK1-4 in mammals. The ribosomal protein S6 Kinase 1 (RSK1) is also known as ribosomal protein S6 kinase alpha-1 (RPS6KA1) is a special protein due to their two catalytic regions that is associated with abundantly various cancers and it is proposed as a drug target. Several RSK1 isoform inhibitors have been reported but none of them are used in clinical studies.

Synthesis, anticancer activity and molecular modeling study of novel substituted triazole linked tetrafluoronaphthalene hybrid derivatives.

To create some novel anticancer molecules, a library of novel series of various triazoles linked to the hydroxyl group of 5,6,7,8-tetrafluoronaphthalen-1-ol was designed and synthesized CuAAC reaction ' of tetrafluoronaphthalene based terminal alkyne with substituted organic azides. The structural characterizations of the targeted Click products were confirmed by FTIR, H NMR, F NMR, C NMR and HRMS spectroscopy. Synthesized compounds were tested in two triple negative breast cancer (TNBC) cell lines to understand their anticancer potentials.

Novel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy.

Eukaryotic elongation factor 2 kinase (eEF2K) has been shown to be an important molecular driver of tumorigenesis and validated as a potential novel molecular target in various solid cancers including triple negative breast cancer (TNBC). Therefore, there has been significant interest in identifying novel inhibitors of eEF2K for the development of targeted therapeutics and clinical translation. Herein, we investigated the effects of indole ring containing derivatives of etodolac, a nonsteroidal anti-inflammatory (NSAID) drug, as potential eEF2K inhibitors and we designed and synthesized seven novel compounds with a pyrano[3,4-] indole core structure.

Identifying highly effective coumarin-based novel cholinesterase inhibitors by in silico and in vitro studies.

Inhibition of high cholinesterase levels including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), is one of the most important strategies for the treatment of Alzheimer's disease (AD). Clinically limited drugs are used in the treatment of AD, so there is a need to find new effective inhibitors today. Therefore, in this study, synthesized six coumarin carboxamides (A1, A2, B1-B4) were evaluated against AChE and BChE by combined in silico and in vitro studies.

Novel inhibitors of eukaryotic elongation factor 2 kinase: In silico, synthesis and in vitro studies.

Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual alpha kinase whose expression is highly upregulated in various cancers and contributes to tumor growth, metastasis, and progression. More importantly, eEF2K expression is associated with poor clinical outcome and shorter patient survival in breast, lung and ovarian cancers. Therefore, eEF2K is an emerging molecular target for development of novel targeted therapeutics and precision medicine in solid cancers.

Correction to "Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth ".

[This corrects the article DOI: 10.1021/acsptsci.1c00030.

Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth .

Eukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications.

Delivery of Small Molecule EF2 Kinase Inhibitor for Breast and Pancreatic Cancer Cells Using Hyaluronic Acid Based Nanogels.

Purpose: To evalauted natural polymeric biomaterials including hyaluronic acid (HA) and its copolymeric form HA:Suc nanoparticles (NPs) as drug carrier systems for delivery of hydrophobic small molecule kinase EF2-kinase inhibitor in breast and pancreatic cancer cells.

Methods: In vitro cellular uptake studies of Rhodamine 6G labaled HA:Suc nanoparticles were evaluated by using flow cytometry analysis and fluorescent microscopy in breast (MDA-MB-231 and MDA-MB-436) and pancreatic cancer cells (PANC-1 and MiaPaca-2). Besides, in vitro release study of compound A (an EF2-kinase inhibitor) as a model hydrophobic drug was performed in the cancer cells.

Design, Synthesis, and Molecular Modeling Studies of Novel Coumarin Carboxamide Derivatives as eEF-2K Inhibitors.

Eukaryotic elongation factor-2 kinase (eEF-2K) is an unusual alpha kinase commonly upregulated in various human cancers, including breast, pancreatic, lung, and brain tumors. We have demonstrated that eEF-2K is relevant to poor prognosis and shorter patient survival in breast and lung cancers and validated it as a molecular target using genetic methods in related tumor models. Although several eEF-2K inhibitors have been published, none of them have shown to be potent and specific enough for translation into clinical trials.

In vitro and in silico studies of nitrobenzamide derivatives as potential anti-neuroinflammatory agents.

Communicated by Ramaswamy H. Sarma.

PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.

The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at cancer cells is remarkable. Discovery of new prodrug/NTR combinations is necessary to be an alternative to known prodrug candidates such as CB1954, SN23862, PR-104A. For this aim, nitro containing aromatic amides (A1-A23) were designed, synthesized, performed in silico ADMET and molecular docking techniques in this study.

Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery.

Porous and biodegradable hyaluronic acid (HA) nanogel and their copolymeric forms with sucrose (Suc), HA:Sucrose (HA:Suc) nanogels, were synthesized by employing glycerol diglycidyl ether (GDE) as crosslinker with a single step reaction in surfactant-free medium. The size of the nanogels was determined as 150 ± 50 nm in dried state from SEM images and found to increase to about 540 ± 47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.

Biological evaluation and molecular docking studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity.

A series of nitro substituted benzamide derivatives were synthesized and evaluated for their potential anti-inflammatory activities in vitro. Firstly, all compounds (1-6) were screened for their inhibitory capacity on LPS induced nitric oxide (NO) production in RAW264.7 macrophages.

Antiproliferative activity of Humulus lupulus extracts on human hepatoma (Hep3B), colon (HT-29) cancer cells and proteases, tyrosinase, β-lactamase enzyme inhibition studies.

The aims of this study were to examine the antiproliferation of Humulus lupulus extracts on human hepatoma carcinoma (Hep3B) and human colon carcinoma (HT-29) cell lines along with enzyme inhibitory effects of the crude extracts. Potential cell cytotoxicity of six different H. lupulus extracts were assayed on various cancer cells using MTT assay at 24, 48 and 72 h intervals.

Comparative study of antioxidant properties and total phenolic content of the extracts of Humulus lupulus L. and quantification of bioactive components by LC-MS/MS and GC-MS.

In this research, antioxidant activities of various extracts obtained from Humulus lupulus L. were compared by DPPH, ABTS, FRAP, and CUPRAC assays. The amount of total phenolic components determined by the Folin-Ciocalteu reagent was found to be highest for 25% aqueous ethanol (9079 ± 187.