51009-60-0Relevant academic research and scientific papers
Design, synthesis, DFT, molecular modelling studies and biological evaluation of novel 3-substituted (E)-5-(arylidene)-1-methyl-2-thioxoimidazolidin-4-ones with potent cytotoxic activities against breast MCF-7, liver HepG2, and lung A549
Awad, Mohamed K.,Bakare, Safyah B.,Khodair, Ahmed I.,Nafie, Mohamed S.
, (2021)
We report the synthesis of novel 3-substituted (E)-5-(arylidene)-1-methyl-2-thioxoimidazolidin-4-ones 6-11, and their biological evaluation. Based on structural and pharmacophore analyses of known inhibitors such as fluorouracil (5-FU), we envisioned interesting 2-thioxoimidazolidin-4-one compounds, 3-substituted (E)-5-(arylidene)-1-methyl-2-thioxoimidazolidin-4-ones 6-11 that would be expected to well match the structural features in 5-FU. Efficient synthesis of twenty-four target compounds 6-11 were achieved through the synthetic pathway of 5 → 6 → 7 → 10 → 11, established after consideration of several plausible synthetic pathways. A series of (E)-5-(arylidene)-1-methyl-2-thioxoimidazolidinoneones 5a-d were synthesized via the reaction of 1-methyl-2-thioxoimidazolidin-4-one (3), which in turn was prepared via the reaction of N-methyl glycine (2) with NH4SCN, followed by Knoevenagel condensation. N-alkylation and N-glycosylation were carried via the reaction of 5a-d with alkyl bromides and α-glycopyranosyl bromides 9a,b under alkaline and glycoside conditions, respectively. The N-alkylated and N-glycosylated structures have been selected for the products. Conformational analysis has been studied by homonuclear and heteronuclear two-dimensional NMR methods (DQF-COSY, HMQC, and HMBC). The N site of alkylation and glycosylation were determined from the 1H, 13C heteronuclear multiple-quantum coherence (HMQC) experiments. Molecular modelling and DFT calculations using B3LYP/6-31+G (d, p) level were performed to study the electronic and geometric properties obtained from the stable structure of the investigated compounds. A good correlation between the quantum chemical descriptors and experimental observations was found. The synthesized derivatives exhibited good binding interactions towards the cyclin-dependent kinase 2, especially compound 11b, which have better key interactions than the co-crystallized ligand. Additionally, it had potent cytotoxic activities with IC50 = 4.30, 5.53, 9.43 against MCF-7, HepG2, and A549, respectively.
Synthesis and structural study of substituted arylideneimidazolidines and arylidenebenzothiazines
Brandao,Guarda,Pitta,Chantegrel,Perrissin,Souza,Galdino,Thomasson,Lima,Leite,Luu-Duc
, p. 54 - 58 (2007/10/03)
Synthesis and physico-chemical properties of six 5-arylidene-3-benzyl-1- methyl-2-thioxoimidazolidin-4-ones and three 2-arylidene-6-nitro-2H-1,4- benzothiazin-3(4H)-ones have been described. These new compounds were synthetised by Knoevenagel condensation
