Design, synthesis, and docking of novel thiazolidine‐2,4‐dione multitarget scaffold as new approach for cancer treatment

Abstract

Novel thiazolidine‐2,4‐diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR‐2 against HCT‐116, MCF‐7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF‐7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF‐7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e–i and 6a–c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR‐2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFRT790M performing strongest effects with IC50 = 0.30, 0.35, 0.50, and 1.00 µM, respectively. What is more, 6a, 6b, and 6c represented satisfactory in silico computed ADMET profile.

Design, synthesis, docking, ADMET and anticancer evaluations of N-alkyl substituted iodoquinazoline derivatives as dual VEGFR-2 and EGFR inhibitors

“…The current investigation is an extension to our preceding work 12,43–51 that reveals the efficacy of the hybridization strategy between iodoquinazolinone and different moieties as EGFR, VEGFR-2 inhibitors and anticancer agents. We designed and synthesized a series of new 6-iodoquinazolinone bearing different moieties with acetamide linker as dual EGFR-mutant/VEGFR-2 inhibitors for the treatment of various cancer types, as liver (HepG2), breast (MCF-7), colorectal (HCT-116) and NSCLC (A549).…”

“…Both VEGFR-2 (PDB ID ) 48,58 and EGFR T790M (PDB ID ) 55,56 were used by Molsoft program to carry out docking studies.…”

“…For molecular docking investigations, Molso soware was used. The PDB IDs for VEGFR-2 (PDB ID 4ASD) 48,58 and EGFR T790M (PDB ID 3W2O) 55,56 were used in each experiment, respectively.…”

Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis

“…In another modification, we thought that if we change the methylene group between the NH 2 and the carbonyl group, we might get better binding results by adding a new hydrogen bonding site (Figure 4). In continuation of our efforts to obtain new immunomodulatory [35][36][37][38][39][40][41][42][43][44] and/or anticancer agents, [45][46][47][48][49][50][51] we designed and synthesized novel thalidomide analogs that were tested in vitro against the HepG-2, HCT-116, PC3, and MCF-7 cancer cell lines. By measuring the immunomodulatory effects of the synthesized compounds in HCT-116 cells against CASP8, TNF-α, VEGF, and NF-κB P65, we conducted additional research to better understand their immunomodulatory effect.…”

“…In continuation of our efforts to obtain new immunomodulatory [ 35–44 ] and/or anticancer agents, [ 45–51 ] we designed and synthesized novel thalidomide analogs that were tested in vitro against the HepG‐2, HCT‐116, PC3, and MCF‐7 cancer cell lines. By measuring the immunomodulatory effects of the synthesized compounds in HCT‐116 cells against CASP8, TNF‐α, VEGF, and NF‐κB P65, we conducted additional research to better understand their immunomodulatory effect.…”