Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction.

Herein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, H and C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the reaction of phenyl hydrazine and ethoxymethylenemalononitrile to give aminopyrazole-carbonitrile 2. The latter hydrolysis with NaOH and subsequent reaction with 4-chlorobenzaldhyde afforded the corresponding pyrazolo[3,4-d]pyrimidin-4-ol 4.

Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers.

Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Percentage inhibition in 14 human cancer cell lines and IC values were recorded. Compounds , and were examined against both wild and mutant (T790M) EGFR subtypes.

Numerical analysis for tangent-hyperbolic micropolar nanofluid flow over an extending layer through a permeable medium.

The principal purpose of the current investigation is to indicate the behavior of the tangent-hyperbolic micropolar nanofluid border sheet across an extending layer through a permeable medium. The model is influenced by a normal uniform magnetic field. Temperature and nanoparticle mass transmission is considered.

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies.

Fifteen quinazoline derivatives were designed and synthesized as DNA intercalators. The cytotoxicity of the designed members was assessed against HCT-116 and HepG2 cancer cell lines. In addition, the topoisomerase II (Topo II) inhibitory effect was assessed.

Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-β/α-SMA upregulation in rats.

In medicine, silver nanoparticles (AgNPs) are employed often. They do, however, have negative impacts, particularly on the reproductive organs. This research aimed to assess AgNP impact on the testis and the possible intracellular mechanisms to induce testicular deteriorations in rats at various concentrations and different time intervals.

Discovery of new 1-pyrazolo[3,4-]pyrimidine derivatives as anticancer agents targeting EGFR and EGFR.

New 1-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesised to act as epidermal growth factor receptor inhibitors (EGFRIs). The synthesised derivatives were assessed for their anti-proliferative activities against A549 and HCT-116 cancer cells. Compounds and showed potent anti-proliferative activities.

Silver nanoparticles induced hepatoxicity via the apoptotic/antiapoptotic pathway with activation of TGFβ-1 and α-SMA triggered liver fibrosis in Sprague Dawley rats.

Despite the extraordinary use of silver nanoparticles (AgNPs) in medicinal purposes and the food industry, there is rising worry about potential hazards to human health and the environment. The existing study aims to assess the hepatotoxic effects of different dosages of AgNPs by evaluating hematobiochemical parameters, oxidative stress, liver morphological alterations, immunohistochemical staining, and gene expression to clarify the mechanism of AgNPs' hepatic toxic potential. Forty male Sprague Dawley rats were randomly assigned into control and three AgNPs intraperitoneally treated groups 0.

Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies.

Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential.

Design, synthesis and anticancer evaluation of 1H-pyrazolo[3,4-d]pyrimidine derivatives as potent EGFR and EGFR inhibitors and apoptosis inducers.

In our attempt to develop effective EGFR-TKIs, two series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated in vitro for their inhibitory activities against EGFR. Compounds 15, 15, and 18 potently inhibited EGFR at sub-micro molar IC values comparable to that of erlotinib.

DDB liver drug as a novel ionophore for potentiometric barium (II) membrane sensor.

Dimethyl-4,4-dimethoxy-5,6,5',6'-dimethylene dioxy biphenyl-2,2-dicarboxylate (DDB) liver drug is used as a novel ionophore in plasticized poly (vinyl chloride) (PVC) matrix membrane sensors for barium ions. Optimum performance characteristics are displayed by membrane sensor incorporating DDB ionophore, potassium tetrakis(4-chlorophenyl)borate as lipophilic salt, and o-nitrophenyloctyl ether as plasticizer. The sensor exhibits a linear response over the concentration range 10(-1)-10(-5) mol l(-1) BaCl(2) with a Nernstian slope of 30 mV per decade and high selectivity towards Ba(2+) with respect to Li(+), Na(+), K(+), Rb(+), NH(4)(+), Mg(2+), Ca(2+), Sr(2+), Mn(2+), Co(2+), Ni(2+), Cd(2+), Al(3+), La(3+), and Ce(3+) ions.