Phthalazine Derivatives as VEGFR-2 Inhibitors: Docking, ADMET, Synthesis, Design, Anticancer Evaluations, and Apoptosis Inducers.

New phthalazine-derived inhibitors for VEGFR-2 were synthesized for anticancer evaluations. Also, docking studies were performed to explore the suggested binding orientations of the novel derivatives inside the binding site of VEGFR-2. The achieved biological data were extremely interrelated to that of docking study.

Rationale, docking, ADMET profile, design, synthesis and cytotoxicity evaluations of phthalazine derivatives as VEGFR-2 inhibitors and apoptosis inducers.

New phthalazine derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors were synthesized joined to different spacers including pyrazole, α,β-unsaturated ketonic fragment, pyrimidinone and/or pyrimidinthione. A docking study was carried out to explore the suggested binding orientations of the novel derivatives inside the active site of VEGFR-2. The obtained biological data were extremely interrelated to that of the docking study.

Exploration of the VEGFR-2 inhibition activity of phthalazine derivatives: design, synthesis, cytotoxicity, ADMET, molecular docking and dynamic simulation.

Novel phthalazine derivatives were designed, synthesized and evaluated against Hep G2 and MCF-7 as VEGFR-2 inhibitors. In particular, compounds 2g and 4a were found to be the most potent derivatives among all the tested compounds against MCF-7 and Hep G2 cancer cell lines with IC values of 0.15 and 0.

New Thieno[2,3-d]pyrimidines as Anticancer VEGFR-2 Inhibitors with Apoptosis Induction: Design, Synthesis, and Biological and Studies.

Background: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a critical protein involved in tumor progression, making it an attractive target for cancer therapy.

Objective: This study aimed to synthesize and evaluate novel thieno[2,3-d]pyrimidine analogues as potential anticancer VEGFR-2 inhibitors.

Methods: The thieno[2,3-]pyrimidine analogues were synthesized following the pharmacophoric features of VEGFR-2 inhibitors.

New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies.

Background: VEGFR-2 has emerged as a prominent positive regulator of cancer progression.

Aim: Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2.

Methods: Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay.

Discovery of new thiazolidine-2,4-dione derivatives as potential VEGFR-2 inhibitors: and studies.

In this study, a series of seven novel 2,4-dioxothiazolidine derivatives with potential anticancer and VEGFR-2 inhibiting abilities were designed and synthesized as VEGFR-2 inhibitors. The synthesized compounds were tested for their potential to inhibit VEGFR-2 and the growth of HepG2 and MCF-7 cancer cell lines. Among the compounds tested, compound (IC = 0.

Synthesis, biological evaluation and computer-aided discovery of new thiazolidine-2,4-dione derivatives as potential antitumor VEGFR-2 inhibitors.

In this study, novel VEGFR-2-targeting thiazolidine-2,4-dione derivatives with potential anticancer properties were designed and synthesized. The ability of the designed derivatives to inhibit VEGFR-2 and stop the growth of three different cancer cell types (HT-29, A-549, and HCT-116) was examined . The IC value of compound 15, 0.

New thiazolidine-2,4-diones as effective anti-proliferative and anti-VEGFR-2 agents: Design, synthesis, in vitro, docking, MD simulations, DFT, ADMET, and toxicity studies.

Novel thiazolidine-2,4-dione derivatives, 11a-g, were designed, and synthesized targeting the VEGFR-2 protein. The in vitro studies indicated the abilities of the synthesized derivatives to inhibit VEGFR-2 and prevent the growth of two different cancer cell types, HepG2 and MCF-7. Compound 11 f exhibited the strongest anti-VEGFR-2 activity (IC = 0.

Discovery of new thieno[2,3-]pyrimidines as EGFR tyrosine kinase inhibitors for cancer treatment.

EGFR has been considered a vital molecular target in cancer management. The discovery of new thieno[2,3-]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Nine derivatives were designed, synthesized and subjected to and studies.

New theobromine derivatives inhibiting VEGFR-2: design, synthesis, antiproliferative, docking and molecular dynamics simulations.

VEGFR-2 is one of the most effective targets in cancer treatment. The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. and evaluation of the synthesized compounds.

Design, synthesis, docking, MD simulations, and anti-proliferative evaluation of thieno[2,3-]pyrimidine derivatives as new EGFR inhibitors.

A group of EGFR inhibitors derived from thieno[2,3-]pyrimidine nucleus was designed, synthesised, and examined as anti-proliferative lead compounds. MCF-7 and A549 cell lines were inhibited by , the most active member. It had inhibitory partialities of 37.

Semi-synthesized anticancer theobromine derivatives targeting VEGFR-2: and evaluations.

Vascular endothelial cell proliferation and angiogenesis are all crucially impacted by Endothelial Growth Factor Receptor-2 (VEGFR-2). Its expression is significantly boosted throughout pathologic angiogenesis causing the development of tumors. Sothat, inhibition of VEGFR-2 has crucial role in cancer treatment.

A novel thieno[2,3-d]pyrimidine derivative inhibiting vascular endothelial growth factor receptor-2: A story of computer-aided drug discovery.

Following the pharmacophoric features of vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors, a novel thieno[2,3-d]pyrimidine derivative has been designed and its activity against VEGFR-2 has been demonstrated by molecular docking studies that showed an accurate binding mode and an excellent binding energy. Furthermore, the recorded binding was confirmed by a series of molecular dynamics simulation studies, which also revealed precise energetic, conformational, and dynamic changes. Additionally, molecular mechanics with generalized Born and surface area solvation and polymer-induced liquid precursors studies were conducted and verified the results of the MD simulations.

Computer aided drug discovery (CADD) of a thieno[2,3-]pyrimidine derivative as a new EGFR inhibitor targeting the ribose pocket.

Depending on the pharmacophoric characteristics of EGFR inhibitors, a new thieno[2,3-d]pyrimidine derivative has been developed. Firstly, the potential inhibitory effect of the designed compound against EGFR has been proven by docking experiments that showed correct binding modes and excellent binding energies of -98.44 and -88.

Synthesis of 1,2,4-Triazinones Exploiting the Reactivity of Diazadiene and -Isocyanate Intermediates.

1,2,4-Triazinones are useful compounds, but their synthesis can be challenging. Herein, we report a strategy to build 1,2,4-triazinones using α-bromohydrazones to access diazadienes and exploiting their ability to undergo facile substitution with nitrogen nucleophiles. The -isocyanate intermediate formed in situ can then undergo cyclization to give the desired triazinones.

New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies.

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects of these compounds were estimated against A549, Caco-2, HepG2, and MDA-MB-231. Compounds and showed comparable activities with doxorubicin against the Caco-2 cells.

Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation.

This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2).

Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, studies, and antiproliferative evaluation.

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (, , , , and ) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member IC = 10.

Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates - was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds , - and showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound.

New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with docking, ADMET, toxicity, and DFT studies.

A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC ranging from 2.3 to 5.

Fludrocortisone Among Adult Renal Transplant Recipients With Persistent Hyperkalemia: Single-Center Experience.

Objectives: Calcineurin inhibitors are the cornerstone of immunosuppression following solid-organ transplant. However, hyperkalemia may occur by multiple mechanisms affecting potassium in the distal tubule. Hyperkalemia is commonly observed in renal transplant recipients, and it is dose-dependent.

New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and studies.

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features of VEGFR-2 inhibitors. Cytotoxic activities were evaluated for all derivatives against two human cancer cell lines, MCF-7 and HepG2. Also, the effect of the most cytotoxic derivatives on VEGFR-2 protein concentration was assessed by ELISA.

Identification of new [1,2,4]triazolo[4,3-a]quinoxalines as potent VEGFR-2 tyrosine kinase inhibitors: Design, synthesis, anticancer evaluation, and in silico studies.

Tumor angiogenesis is mainly regulated by VEGFR-2. In this study, a new series of [1,2,4]triazolo[4,3-a]quinoxaline based-derivatives has been designed and synthesized to develop new anti-proliferative and anti-VEGFR-2 members. Anti-proliferative activities of the synthesized compounds were tested against MCF-7 and HepG2 cell lines.

New bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation.

A new series of bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives were designed and synthesized to have the main essential pharmacophoric features of VEGFR-2 inhibitors. VEGFR-2 inhibitory activities were assessed for the designed compounds. In addition, cytotoxic activity was evaluated for all derivatives against two human cancer cell lines namely, HepG-2 and MCF-7.

Design and discovery of new antiproliferative 1,2,4-triazin-3(2H)-ones as tubulin polymerization inhibitors targeting colchicine binding site.

Thirty-five new colchicine binding site inhibitors have been designed and synthesized based on the 1,2,4-triazin-3(2H)-one nucleus. Such molecules were synthesized through a cascade reaction between readily accessible α-amino ketones and phenyl carbazate as a masked N-isocyanate precursor. The synthesized derivatives are cisoid restricted combretastatin A4 analogues containing 1,2,4-triazin-3(2H)-one in place of the olefinic bond, and they have the same essential pharmacophoric features of colchicine binding site inhibitors.