Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery. Development of novel nicotinamides as VEGFR-2 inhibitors. different and assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.

New Theobromine Apoptotic Analogue with Anticancer Potential Targeting the EGFR Protein: Computational and Studies.

Aim: The aim of this study was to design and examine a novel epidermal growth factor receptor (EGFR) inhibitor with apoptotic properties by utilizing the essential structural characteristics of existing EGFR inhibitors as a foundation.

Method: The study began with the natural alkaloid theobromine and developed a new semisynthetic derivative (). Computational ADMET assessments were conducted first to evaluate its anticipated safety and general drug-likeness.

New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, , and studies.

Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members , , , and were estimated against their selected target (VEGFR-2).

Computer-Assisted Drug Discovery of a Novel Theobromine Derivative as an EGFR Protein-Targeted Apoptosis Inducer.

The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with the aim of reducing its proliferation and inducing apoptosis. This study aimed at the CADD of a new apoptotic EGFR inhibitor. The natural alkaloid, theobromine, was used as a starting point to obtain a new semisynthetic (di-ortho-chloro acetamide) derivative ().

Design, Molecular Modeling, MD Simulations, Essential Dynamics, ADMET, DFT, Synthesis, Anti-proliferative, and Apoptotic Evaluations of a New Anti-VEGFR-2 Nicotinamide Analogue.

Objectives: This study aims to design and evaluate ( and ) a new nicotinamide derivative as an inhibitor of VEGFR-2, a major mediator of angiogenesis Methods: The following studies were performed; DFT calculations, molecular modelling, MD simulations, MM-GBSA, PLIP, and PCAT studies. The compound's (ADMET) analysis was also conducted. Subsequently, the compound ((E)--(4-(1-(2-(4-(4-Chlorobenzamido)benzoyl)hydrazono)ethyl) phenyl)nicotinamide) was successfully synthesized and designated as compound .

Computer-assisted drug discovery (CADD) of an anti-cancer derivative of the theobromine alkaloid inhibiting VEGFR-2.

VEGFR-2 is a significant target in cancer treatment, inhibiting angiogenesis and impeding tumor growth. Utilizing the essential pharmacophoric structural properties, a new semi-synthetic theobromine analogue () was designed as VEGFR-2 inhibitor. Firstly, 's stability and reactivity were indicated through several DFT computations.

Exploring the anticancer properties of a new nicotinamide analogue: Investigations into in silico analysis, antiproliferative effects, selectivity, VEGFR-2 inhibition, apoptosis induction, and migration suppression.

Background: This study focuses on the development and evaluation of (E)-N-(3-(1-(2-(4-bromobenzoyl)hydrazono)ethyl)phenyl)nicotinamide (BHEPN) as a potential inhibitor of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2).

Methods: Computational investigations as density function theory (DFT), docking, molecular dynamics (MD) simulations, and ADMET) in addition to in vitro (VEGFR-2 inhibition, cytotoxicity against HepG2 and MCF-7 cancer cell lines, selectivity index, cells cycle analysis, apoptosis investigation, and cells migration assay) studies were conducted.

Results: DFT calculations determined the three-dimensional structure and indicated the reactivity of BHEPN.

Anti-breast cancer potential of a new xanthine derivative: In silico, antiproliferative, selectivity, VEGFR-2 inhibition, apoptosis induction and migration inhibition studies.

Background: The overexpression of VEGFR-2 receptors in breast cancer provides a valuable approach to anticancer strategies. Targeting VEGFR-2, a new semisynthetic compound (T-1-MCPAB) has been designed.

Methods: Computational methods (ADMET, toxicity, DFT, Molecular Docking, Molecular Dynamics Simulations, MM-GBSA, PLIP, and PCAT) were conducted.

A Theobromine Derivative with Anticancer Properties Targeting VEGFR-2: Semisynthesis, in silico and in vitro Studies.

A computer-assisted drug design (CADD) approach was utilized to design a new acetamido-N-(para-fluorophenyl)benzamide) derivative of the naturally occurring alkaloid, theobromine, (T-1-APFPB), following the pharmacophoric features of VEGFR-2 inhibitors. The stability and reactivity of T-1-AFPB were assessed through density functional theory (DFT) calculations. Molecular docking assessments showed T-1-AFPB's potential to bind with and inhibit VEGFR-2.

Design, semi-synthesis, anti-cancer assessment, docking, MD simulation, and DFT studies of novel theobromine-based derivatives as VEGFR-2 inhibitors and apoptosis inducers.

A group of theobromine derivatives was designed based on the key pharmacophoric characteristics of VEGFR-2 inhibitors. HepG2 and MCF-7 cancer cell lines were used to test the obtained compounds for their in vitro anti-proliferative activities. Compound 15 (2-(3,7-Dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-(4-(1-(2-(4-hydroxybenzoyl)hydrazono)ethyl) phenyl)acetamide) was the most potent cytotoxic member against MCF-7 (IC = 0.

New apoptotic anti-triple-negative breast cancer theobromine derivative inhibiting EGFRWT and EGFR: in silico and in vitro evaluation.

A new theobromine-derived EGFR inhibitor (2-(3,7-Dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)-N-(2,6-dimethylphenyl)acetamide) has been developed that has the essential structural characteristics to interact with EGFR's pocket. The designed compound is 2,6-di ortho methylphenyl)acetamide derivative of the well-known alkaloid, theobromine, (T-1-DOMPA). Firstly, deep DFT studies have been conducted to study the optimized chemical structure, molecular orbital and chemical reactivity analysis of T-1-DOMPA.

A New Anticancer Semisynthetic Theobromine Derivative Targeting EGFR Protein: CADDD Study.

A new lead compound has been designed as an antiangiogenic EGFR inhibitor that has the pharmacophoric characteristics to bind with the catalytic pocket of EGFR protein. The designed lead compound is a (para-chloro)acetamide derivative of the alkaloid, theobromine, (). At first, we started with deep density functional theory (DFT) calculations for to confirm and optimize its 3D structure.

()--(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide: A Novel Pyridine Derivative for Inhibiting Vascular Endothelial Growth Factor Receptor-2: Synthesis, Computational, and Anticancer Studies.

()--(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide (compound ) was designed as an antiangiogenic VEGFR-2 inhibitor with the essential pharmacophoric structural properties to interact with the catalytic pocket of VEGFR-2. The designed derivative was synthesized, and its structure was confirmed through Ms, elemental, H, and C spectral data. The potentiality of the designed pyridine derivative to bind with and inhibit the vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme was indicated by molecular docking assessments.

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities.

, VEGFR-2 inhibition, and anticancer activity of a 3-(hydrazonomethyl)naphthalene-2-ol derivative.

In agreement with the general features of VEGFR-2 inhibitors, a new naphthalene analog (compound ) has been designed and synthesized. The inhibitory potential of compound was indicated by the proper binding and the perfect energy of -21.10 kcal/mol compared to sorafenib (-21.

New Anticancer Theobromine Derivative Targeting EGFR and EGFR: Design, Semi-Synthesis, In Silico, and In Vitro Anticancer Studies.

Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFR; PDB: 4HJO) and mutant (EGFR; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics.

Anti-cancer and immunomodulatory evaluation of new nicotinamide derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: and studies.

New nicotinamide derivatives , , , and were designed and synthesised based on the essential features of the VEGFR-2 inhibitors. Compound revealed the highest anti-proliferative activities with IC values of 15.4 and 9.

Design, Synthesis, In Silico and In Vitro Studies of New Immunomodulatory Anticancer Nicotinamide Derivatives Targeting VEGFR-2.

VEGFR-2, the subtype receptor tyrosine kinase (RTK) responsible for angiogenesis, is expressed in various cancer cells. Thus, VEGFER-2 inhibition is an efficient approach for the discovery of new anticancer agents. Accordingly, a new set of nicotinamide derivatives were designed and synthesized to be VEGFR-2 inhibitors.

Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies.

A library of modified VEGFR-2 inhibitors was designed as VEGFR-2 inhibitors. Virtual screening was conducted for the hypothetical library using docking, ADMET, and toxicity studies. Four compounds exhibited high affinity against VEGFR-2 and an acceptable range of the drug-likeness.

Inhibition of Vascular Smooth Muscle and Cancer Cell Proliferation by New VEGFR Inhibitors and Their Immunomodulator Effect: Design, Synthesis, and Biological Evaluation.

Abnormal vascular smooth muscle cell (VSMC) proliferation has an important role in the pathogenesis of both atherosclerosis restenosis and hypertension. Vascular endothelial growth factor (VEGF) has been shown to stimulate VSMC proliferation. In addition, angiogenesis is one of the hallmarks of cancerous growth.

Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation.

VEGF/VEGFR2 pathway is the crucial therapeutic target in the treatment of cancer. So that, a new series of quinoxaline-2(1H)-one derivatives were designed and synthesized. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) aiming to evaluate its anti-proliferative activities.