Molecular dynamics simulation and 3D-pharmacophore analysis of new quinoline-based analogues with dual potential against EGFR and VEGFR-2

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

“…The docking study was performed on DNA to predict the binding affinity and the interactions of compounds 14g and 16c using mitoxantrone 48,49 for interaction with DNA (1BNA). Based on the fact that 2-chloro-4-anilinoquinazoline derivatives have been reported as anticancer agents to target the EGFR and VEGFR-2 receptors, 9,12,13 we also performed the studies of docking of compounds 14g, 16a and 16c into the active site of the EGFR (PDB: 1XKK) and VEGFR-2 (PDB: 4ASE). Two controls were taken for both EGFR (getinib and lapatinib) and VEGFR-2 (sorafenib and tivozanib) receptors.…”

“…2, dual EGFR and VEGFR-2 inhibitors containing the 2-chloro-quinazoline core are shown. 9 Although, quinazoline derivatives have exhibited high affinity and selectivity as tyrosine kinase inhibitors (TKIs), those compounds can interact with double-stranded DNA due to their planar conjugated system through intercalation and groove binding to DNA 14 with recognition mainly for GC-rich sequences. 15 These types of interactions lead to cell death by disrupting replication and transcription.…”

“…Recently, computational approaches and rational strategies have allowed the design of ligands directed toward multiple therapeutic targets as an alternative to traditional pharmacological therapy. 9 Although, the main target of 4-anilinoquinazolines is the EGFR, 1,10,11 some derivatives also target several kinases due to the similarities of their binding pockets 6 such as B-Raf, phosphoinositide 3-kinase (PI3K), HER2 and, vascular endothelial growth factor (VEGFR-2), as well as the dual inhibitors afatinib (EGFR/HER2), lapatinib (EGFR/HER2) and vandetanib (EGFR/VEGFR-2). 10 Among recently reported examples, 2-chloro-4-anilinoquinazolines with heterocyclylsulfonamido moiety have shown antitumor activity (1–2, Fig.…”

Report on Recently (2017–20) Designed Quinoline‐Based Human Cancer Cell Growth Inhibitors

“…Illustration of heterocyclic-ring comprising quinolines. [84][85][86][87][88][89] ylquinoline and 6-methoxyquinoline analogs. Irrespective of the substituent at position-2 of the quinoline and aryl substituent on triazolone, all 2-chloroquinoline derivatives have failed to display decent growth inhibitory effects.…”

“…4-Amino-7-chloroquinoline derivatives attached with benzyloxy-pyrimidinone moiety through propyl chain were prepared to assess antiproliferative activity. [85] The three derivatives synthesized were evaluated for anticancer activity against A549, HT29, MCF-7, and AGO1522 cell growth. Amongst the three derivatives, 4-amino-7-chloroquinoline analog 48 (Figure 5) bearing chloromethyl substituted pyrimidinone ring has rendered the best anticancer activity (IC 50 = 0.81-2.87 μM) against the growth of all the cell lines.…”