Design, synthesis, and in silico insights of novel N'-(2-oxoindolin-3-ylidene)piperidine-4-carbohydrazide derivatives as VEGFR-2 inhibitors.

Vascular endothelial growth factor (VEGF) is a crucial key factor in breast tumorigenesis. VEGF plays an important role in angiogenesis, tumor proliferation, and metastasis. Herein, we report the design and synthesis of twenty-one novel piperidine/oxindole derivatives as potential VEGFR-2 inhibitors.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expression of oncogenic proteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agents for NSCLC.

Acridinedione-phthalimide conjugates: Intramolecular electron transfer and singlet oxygen generation studies for optical and photodynamic therapy applications.

We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione-phthalimide connected molecules (AcrPhth 1-5) have been examined utilizing various spectroscopic techniques, e.

Toxicity of bisphenol A and -nitrophenol on tomato plants: Morpho-physiological, ionomic profile, and antioxidants/defense-related gene expression studies.

Bisphenol A (BPA) and -nitrophenol (PNP) are emerging contaminants of soils due to their wide presence in agricultural and industrial products. Thus, the present study aimed to integrate morpho-physiological, ionic homeostasis, and defense- and antioxidant-related genes in the response of tomato plants to BPA or PNP stress, an area of research that has been scarcely studied. In this work, increasing the levels of BPA and PNP in the soil intensified their drastic effects on the biomass and photosynthetic pigments of tomato plants.

Phytochemical and biological assessment of secondary metabolites isolated from a rhizosphere strain, Sphingomonas sanguinis DM of Datura metel.

Background: The plant roots excrete a large number of organic compounds into the soil. The rhizosphere, a thin soil zone around the roots, is a hotspot for microbial activity, making it a crucial component of the soil ecosystem. Secondary metabolites produced by rhizospheric Sphingomonas sanguinis DM have sparked significant curiosity in investigating their possible biological impacts.

Revealing the diversity of Jojoba-associated fungi using amplicon metagenome approach and assessing the in vitro biocontrol activity of its cultivable community.

Jojoba shrubs are wild plants cultivated in arid and semiarid lands and characterized by tolerance to drought, salinity, and high temperatures. Fungi associated with such plants may be attributed to the tolerance of host plants against biotic stress in addition to the promotion of plant growth. Previous studies showed the importance of jojoba as jojoba oil in the agricultural field; however, no prior study discussed the role of jojoba-associated fungi (JAF) in reflecting plant health and the possibility of using JAF in biocontrol.

Assessment of the therapeutic potential of a novel phosphoramidate acyclic nucleoside on induced hepatocellular carcinoma in rat model.

Aims: Hepatocellular Carcinoma (HCC) is renowned as a deadly primary cancer of hepatic origin. Sorafenib is the drug-of-choice for targeted treatment of unresectable end-stage HCC. Unfortunately, great proportion of HCC patients showed intolerance or unresponsiveness to treatment.

Quality-by-design ecofriendly potentiometric sensor for rapid monitoring of hydroxychloroquine purity in the presence of toxic impurities.

Hydroxychloroquine (HCQ) is prescribed to treat malaria and certain autoimmune diseases. Recent studies questioned its efficiency in relieving COVID-19 symptoms and improving clinical outcomes. This work presents a quality-by-design approach to develop, optimize, and validate a potentiometric sensor for the selective analysis of HCQ in the presence of its toxic impurities (key starting materials), namely 4,7-Dichloroquinoline (DCQ) and hydroxynovaldiamine (HND).

Novel -Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations.

Significant advancements have been made in the domain of targeted anticancer therapy for the management of malignancies in recent times. VEGFR-2 is characterised by its pivotal involvement in angiogenesis and subsequent mechanisms that promote tumour cells survival. Herein, novel -arylmethyl-aniline/chalcone hybrids were designed and synthesised as potential anticancer and VEGFR-2 inhibitors.

Synthesis and cytotoxicity evaluation of novel 1,8-acridinedione derivatives bearing phthalimide moiety as potential antitumor agents.

In this study, we aimed to develop hybrid antitumor compounds by synthesizing and characterizing novel N-substituted acrididine-1,8-dione derivatives, designed as hybrids of phthalimide and acridine-1,8-diones. We employed a three-step synthetic strategy and characterized all compounds using IR, H NMR, C NMR, and LC-MS. The cytotoxicity and antitumor activity of five compounds (8c, 8f, 8h, 8i, and 8L) against four cancer cell lines (H460, A431, A549, and MDA-MB-231) compared to human skin fibroblast cells were evaluated.

Novel hydrazone-isatin derivatives as potential EGFR inhibitors: Synthesis and in vitro pharmacological profiling.

Merging isatin and arylhydrazone moieties constitutes an efficient strategy to access new potential anticancer derivatives. Consequently, 14 hydrazone-isatin derivatives were synthesized and evaluated for their antiproliferative activity against the NCI-60 cancer cell line panel. A kinase assay demonstrated that compound VIIIb inhibited the epidermal growth factor receptor (EGFR), which was confirmed by docking studies, molecular dynamics, and binding free energy calculations.

A sustainable approach for the degradation kinetics study and stability assay of the SARS-CoV-2 oral antiviral drug Molnupiravir.

Molnupiravir (MPV) is the first direct-acting oral antiviral drug that effectively decreases nasopharyngeal infections with SARS-CoV-2 virus. The stability of MPV was tested by subjecting the drug to various stress conditions. The drug is liable to oxidative, acidic, and alkaline degradation and showed significant stability against thermal degradation.

A Novel Nanoemulsion Formula for an Improved Delivery of a Thalidomide Analogue to Triple-Negative Breast Cancer; Synthesis, Formulation, Characterization and Molecular Studies.

Background: Thalidomide (THD) and its analogues were recently reported as a promising treatment for different types of solid tumors due to their antiangiogenic effect.

Methods: In this work, we synthesized a novel THD analogue (TA), and its chemistry was confirmed with different techniques such as IR, mass spectroscopy, elemental analysis as well as H and C NMR. To increase solubility and anticancer efficacy, a new oil in water (O/W) nanoemulsion (NE) was used in the formulation of the analogue.

3-Substituted-2,3-Dihydrothiazole as a promising scaffold to design EGFR inhibitors.

The overexpression of EGFR has been recognized as the driver mechanism in the development of several human malignancies and the clinical use of EGFR inhibitors currently constitutes the standard of care for a wide range of malignancies, including colorectal cancer. However, the clinical efficacy of EGFR targeted inhibitors is limited by the development of intrinsic or acquired resistance, requiring the discovery of new compounds with different structural characteristics from those already developed. In this context, we explored the replacement of the aminoquinazoline pharmacophore of several FDA-approved EGFR inhibitors by its bioisosteric hydrazinothiazole moiety.

Assessment of the Anticancer Potentials of the Free and Metal-Organic Framework (UiO-66) - Delivered Phycocyanobilin.

Phycocyanin (C-PC) is a constitutive chromoprotein of Arthrospira platensis, which exhibits promising efficacy against different types of cancer. In this study, we cleaved C-PC's chromophore phycocyanobilin (PCB) and demonstrated its ability as an anti-cancer drug for Colorectal cancer (CRC). PCB displayed an anti-cancer effect for CRC (HT-29) cells with IC50 of 108 µg/ml.

Intensification of resveratrol cytotoxicity, pro-apoptosis, oxidant potentials in human colorectal carcinoma HCT-116 cells using zein nanoparticles.

Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells.

Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with antitumor activity towards non-small lung cancer.

New series of thiazolyl-pyrazoline derivatives (, and ) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds and exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC = 40.7 ± 1.

Synthesis of novel pyridine and pyrimidine thioglycoside phosphoramidates for the treatment of COVID-19 and influenza A viruses.

A novel series of pyridine, cytosine, and uracil thioglycoside analogs ( and respectively) and their corresponding phosphoramidates ( and respectively) were synthesized and assessed for their antiviral inhibitory activities in a dual-pathogen screening protocol against SARS-CoV-2 and influenza A virus (IAV). MTT cytotoxicity (TC50) and plaque reduction assays were used to explore inhibition and cytotoxicity percentage values for H5N1 influenza virus strain and the half-maximal cytotoxic concentration (CC) and inhibitory concentration (IC) for SARS-CoV-2 virus. Most of the tested compounds demonstrated dose-dependent inhibition behavior.

Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment.

A new series of sixteen new 2-arylamino-5,7-disubstituted-N-aryl-pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives was designed and synthesized. The antitumor activities of the new compounds were initially screened through the developmental therapeutics program at NCI-USA 60 cell line panel. 2-((2,4-dimethoxyphenyl)amino)-5,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7a) was identified as a potential hit with a mean percentage of growth inhibition of 48.

Synthesis, in vitro biological investigation, and molecular dynamics simulations of thiazolopyrimidine based compounds as corticotrophin releasing factor receptor-1 antagonists.

Corticotrophin releasing factor receptor-1 (CRFR1) is a potential target for treatment of depression and anxiety through modifying stress response. A series of new thiazolo[4,5-d]pyrimidine derivatives were designed, prepared and biologically evaluated as potential CRFR1 antagonists. Four compounds produced more than fifty percent inhibition in the [I]-Tyr-sauvagine specific binding assay.

An investigative study of antitumor properties of a novel thiazolo[4,5-d]pyrimidine small molecule revealing superior antitumor activity with CDK1 selectivity and potent pro-apoptotic properties.

New thiazolo[4,5-d]pyrimidine analogues were synthesized and biologically assessed in-vitro for their antineoplastic activity. The growth inhibitory effects of these compounds were assessed through the National Cancer Institute-United States of America (NCI-USA) anticancer screening program. Compound5(7-Chloro-3-(2,4-dimethoxyphenyl)-5-methylthiazolo[4,5-d]pyrimidine-2(3H)-thione) was found to have a potent and broad-spectrum cytotoxic action against NCI panel with GI (50% growth inhibition concentration) mean graph midpoint (MG-MID) = 2.

Sofosbuvir Thio-analogues: Synthesis and Antiviral Evaluation of the First Novel Pyridine- and Pyrimidine-Based Thioglycoside Phosphoramidates.

The synthesis and antiviral screening of the first reported series of pyridine- and pyrimidine-based thioglycoside phosphoramidates are herein reported. They were prepared through two synthetic steps: The first step is via coupling of mercapto-derivatized heterocyclic bases with the appropriate α-bromo per-acetylated sugars. The second one is the hydrolysis of the acetate esters under basic conditions that were consequently conjugated with the phosphoramidating reagent to afford the desired thioglycoside protides.

Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs with Dual Biological Active Sites.

The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods.