New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Abstract

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e , 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

“…ADMET prediction has been extensively used to obtain insights about the pharmacokinetic properties of drug-like compounds. , In the case of compound 5b , both predicted values in the PkCSM server and PreADMET showed that human intestinal absorption was 100 and 97.83%, respectively. The compounds showed a reasonable volume of distribution and skin permeability.…”

Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations

“…PV 3D structure was retrieved from PDB using the code:4O6E, and the 3D structure of PV was retrieved from PubChem in SDF format. Leadit software 2.8 was used as previously reported [61][62][63] and it showed RMSD = 1.3Å after redocking the co-crystallized ligand indicating its validity.…”

Discovery of sulfonamide-tethered isatin derivatives as novel anticancer agents and VEGFR-2 inhibitors

“…The NCI-USA antitumor assessment 39 , MTT viability 40 , 41 , VEGFR-2 inhibition 42 , 43 , CA I, II, and IX inhibition studies 44–47 , cell cycle analysis and annexin V-FITC apoptosis assay 48 , 49 were all carried out as previously published in the current study. The supplementary data included descriptions of every experimental technique.…”