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

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact catalytic pocket. The ability of congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, bind enzyme demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established excellent binding 10 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed proper a total exact energy...

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids potential activity against VEGFR-2. The cytotoxic effects of synthesised derivatives Caco-2, HepG-2, MDA-MB-231 cell lines were investigated. Compound 12a found be most potent candidate investigated IC50 values 2, 10, 40 µM, respectively. Furthermore, tested in vitro for their VEGFR-2 inhibitory showing strong inhibition....

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a critical role in cancer angiogenesis. Inhibition of VEGFR-2 activity proved effective suppression tumour propagation. Accordingly, two series new 3-methylquinoxaline derivatives have been designed and synthesised as inhibitors. The were evaluated vitro for their cytotoxic activities against MCF-7and HepG2 cell lines. In addition, the inhibitory target compounds estimated to indicate potential mechanism cytotoxicity. To great...

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 HepG-2. Compounds 15b 17b demonstrated a significant effect with IC50 ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out all tested candidates VEGFR-2. Compound most potent inhibitor (IC50 = 2.7 nM). Mechanistic investigation including...

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, molecular structure similarity study done with PRD_002214, co-crystallized ligand Mpro (PDB ID: 6LU7), favored thirty Subsequently, fingerprint...

Abstract Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles cancer progression survive. In this respect, new series of pyrazole-thiazol-4-one hybrids ( 9a–p ) were synthesized as potential anticancer agents. All molecules exhibited antiproliferative actions...

Corresponding to the reported features of anti-VEGFR-2-approved compounds, a new 1H-indole derivative (compound 7) was designed. The inhibitory potential designed compound revealed via molecular docking study that showed appropriate binding. Then, MD simulation (six studies) over period 100 ns performed confirm precise binding and optimum energy. Additionally, MM-GBSA reaffirmed perfect binding, exhibiting total energy −40.38 Kcal/Mol. experiments named essential amino acids in...

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

Among a group of 310 natural antiviral metabolites, our team identified three compounds as the most potent inhibitors against SARS-CoV-2 main protease (PDB ID: 5R84), Mpro. The are sattazolin and caprolactin A B. validated multistage in silico study was conducted using several techniques. First, molecular structures selected metabolites were compared with that GWS, co-crystallized ligand Mpro, structural similarity study. aim this to determine thirty similar (10%) may bind Mpro GWS. Then,...

A new series of 1H-pyrrole (6a-c, 8a-c), pyrrolo[3,2-d]pyrimidines (9a-c) and pyrrolo[3,2-e][1, 4]diazepines (11a-c) were designed synthesised. These compounds to have the essential pharmacophoric features EGFR Inhibitors, they shown anticancer activities against HCT116, MCF-7 Hep3B cancer cells with IC50 values ranging from 0.009 2.195 µM. value doxorubicin is 0.008 µM, 9a 9c showed 0.011 µM respectively HCT-116 cells. Compound 8b exerted broad-spectrum activity all tested cell lines an...

We report herein, the design and synthesis of thiazolidine-2,4-diones derivatives as new inhibitors for VEGFR-2. The designed members were assessed their in vitro anticancer activity against four cancer cell lines; A549, Caco-2, HepG-2 MDA-MB-231. Compound 14a showed most potent effects lines (IC50 = 1.5 31.5 μM, respectively). Next, VEGFR-2 inhibitory activity, safety profiles selectivity indices examined all synthesized normal Vero line. (the safest member Caco-2 line) was further...

A new set of quinoline and isatine derivatives were synthesized as antiangiogenic VEGFR-2 inhibitors. On a biological level, the in vitro ability obtained candidates to inhibit was found be strong with IC50 values range 76.64-175.50 nM. To investigate cytotoxicity safety, all compounds tested against panel four cancer cell lines (A549, Caco2, HepG2 MDA) well two normal (Vero WI-38). Interestingly, compound 12 exhibited noticeable A549, Caco2 MDA 5.40, 0.58 0.94 µM, respectively. These...

Abstract A new series of 2‐substituted‐2,3‐dihydrophthalazine‐1,4‐diones ( 2 ‒ 9 ) were designed and synthesized to evaluate their anticonvulsant activity. The neurotoxicity was assessed using the rotarod test. Molecular docking performed for compounds assess binding affinities as γ‐aminobutyric acid (GABA‐A) receptor agonists a possible mechanism action, rationalize activity in qualitative way. data obtained from molecular modeling strongly matched with that biological screening, which...

Novel benzamide derivatives as anti adenovirus, HSV-1, coxsackievirus, and SARS-CoV-2: in vitro silico study.

Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised were biologically investigated for their cytotoxic activities against HepG2 MCF-7. Also, the tested compounds further examined in vitro VEGFR-2 inhibitory activity. most promising derivative 23j was its apoptotic behaviour cell lines using flow cytometric western-plot analyses. Additional in-silico studies performed to predict how can bind...

Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both MMP-2 MMP-9 proteins find most promising inhibitors as proposed computational treat keratoconus. Matrix metalloproteinases (MMPs) zinc-dependent proteases, MMP (MMPIs) usually designed interact with zinc ion in...

(E)-N-(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide (compound 10) was designed as an antiangiogenic VEGFR-2 inhibitor with the essential pharmacophoric structural properties to interact catalytic pocket of VEGFR-2. The derivative synthesized, and its structure confirmed through Ms, elemental, 1H, 13C spectral data. potentiality pyridine bind inhibit vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme indicated by molecular docking assessments....

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, 13a) displayed high growth inhibitory activities against HepG2 MCF-7 cell lines further investigated for their activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 μM 15.21 MCF-7, respectively) had the promising activity 97.38 nM). A biological evaluation revealed that compound 12l could arrest...