Synthesis and screening of novel 4-N-heterocyclic-2-aryl-6,7,8-trimethoxyquinazolines as antiproliferative and tubulin polymerization inhibitors

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo

“…Results from docking studies of compounds with tubulin protein (PDB entry: 1SA0) showed that both colchicine and CMH were well fitted in the colchicine binding site of tubulin. Specifically, colchicine molecule formed a hydrogen bond to Asn258 of tubulin protein with an estimated binding free energy of -5.93 kcal/mol, an observation consistent with an earlier study (colchicine docking score: −5.5 kcal/mol) (Dwivedi et al, 2022). In contrast, the best-docked conformation of CMH in the tubulin showed that the methoxy and the phenolic hydroxyl group of this ligand from the colchicine fragment and B fragment interacted with Asn258 and Thr353 through several hydrogen bonds with an estimated binding free energy of -8.04 kcal/mol (Figure 7).…”

Caesium carbonate promoted regioselective O-functionalization of 4,6-diphenylpyrimidin-2(1H)-ones under mild conditions and mechanistic insight

“…The synthesized compounds are being screened for multi-potent activity against different targets for the treatment of Alzheimer's disease. 10,11,[31][32][33][34][35][36][37] In continuation of this, we got interested in the functionalization of pyrimidine and quinazoline with propargyl bromide. Initially, propargyl bromide mediated alkylation of 6-bis(4-methoxyphenyl)pyrimidin-2(1H)-one (1) was attempted using K 2 CO 3 and dimethyl formamide (DMF) as solvent.…”

Recent updates in click and computational chemistry for drug discovery and development

“…To effectively and efficiently design and develop new drugs, computational methods had been applied for drug design including target identification, seeking out and optimizing lead compounds prediction of pharmacokinetic and toxicological properties as well as compound synthesis by molecular docking and molecular dynamics, virtual screening, pharmacophore and ADMET prediction. Novel quinazoline derivative 1 as tubulin polymerization inhibitor ( Dwivedi et al, 2022 ), PARP-1 inhibitor 2 ( Syam et al, 2022 ), CDK2 inhibitor 3 ( Qayed et al, 2022 ), HDAC-1-3 inhibitor 4 ( Cheshmazar et al, 2022 ), VEGFR-2 inhibitor 5 ( Taghour et al, 2022 ) were identified for cancer therapies. Furthermore, AChE inhibitor 6 ( Macedo Vaz et al, 2022 ) for treatment of Alzheimer’s disease and Mtb RNAP inhibitor 7 ( Mekonnen Sanka et al, 2022 ) for antitubercular and antimicrobial treatment were deserve further study.…”