603-23-6Relevant academic research and scientific papers
Design, synthesis, biological evaluation, and molecular docking study of thioxo-2,3-dihydroquinazolinone derivative as tyrosinase inhibitors
Adibi, Hossein,Asgari, Mohammad Sadegh,Attarroshan, Mahshid,Farid, Sara Moghadam,Hamedifar, Haleh,Hosseini, Samanesadat,Iraji, Aida,Kabiri, Maryam,Khoshneviszadeh, Mehdi,Larijani, Bagher,Mahdavi, Mohammad,Moayedi, Seyedeh Sara,Moazzam, Ali,Pirhadi, Somayeh,Sakhteman, AmirHossein,Sepehri, Nima
, (2022/01/11)
Tyrosinase is known to be a key enzyme in melanogenesis and hyperpigmentation. In this study, a series of thioxo-dihydroquinazolinone compounds were designed and synthesized as tyrosinase inhibitors. Among the investigated compounds, 4m demonstrated the best inhibitory activity with an IC50 value of 15.48 μM compared to kojic acid as a positive control with IC50 value of 9.30 μM. In kinetic evaluation against tyrosinase, 4m depicted a mixed inhibition pattern. Additionally, antioxidant evaluations exhibited moderate to weak potency in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The detailed interactions and binding mode toward tyrosinase of the most potent derivative were explicated by molecular docking study. Moreover, the computer-aided drug-likeness and pharmacokinetic studies were also carried out.
Remarkable conversion of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones into the corresponding quinazoline-2,4(1H,3H)-diones: Spectroscopic analysis and X-ray crystallography
El-Azab, Adel S.,Khalil, Nasr Y.,Abdel-Aziz, Alaa A.-M.
, (2021/04/26)
A simple and efficient new synthetic method to obtain 3-substituted quinazolin-2,4-diones 9.16 by the reaction of 3-substituted 2- thioxo-quinazolin-4-ones 1.8 with sodamide under mild conditions was presented. The structure of the newly synthesized compounds was determined by infrared spectroscopy, UV-visible spectroscopy, nuclear magnetic resonance, and single-crystal X-ray crystallographic analysis. The crystal structure of 6-methyl-3-phenylquinazoline-2,4(1H,3H)-dione (11) [C15H12N2O2: MF. 252.27, triclinic, P-1, a = 7.8495 (13) ?, b= 12.456 (2) ?, c = 13.350 (2) ?, α = 103.322 (3)°, β = 90.002 (3)°, γ = 102.671 (4)°, V. 1237.5 (3) ?3, Z= 4, R = 0.0592, wR= 0.1699, S= 1.039] was determined. In the crystal cell, two identical conformers of compound 11 were found connected by intramolecular hydrogen bonds, responsible for the favourable occurrence of these two independent molecules.
Synthesis, biological evaluation and molecular docking of 3-substituted quinazoline-2,4(1H, 3H)-diones
Bastidas, Pedro,Calderón-Zamora, Loranda,García-Páez, Fernando,Ochoa-Terán, Adrián,Osuna-Martínez, Ulises,Picos-Corrales, Lorenzo A,Rendón-Maldonado, Guadalupe,Santos-Ballardo, Lumadhar,Sarmiento-Sánchez, Juan I
, (2020/08/14)
Abstract: The quinazoline-2,4-diones scaffold is found in bioactive compounds, commercial drugs and exhibit important biological activities. However, their antidiabetic activity is rarely explored. For this purpose, an easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Additionally, the synthesized compounds were screened for in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity. The quinazoline-2,4-diones were isolated, with yields in the range of 30-65percent. The compounds 3d, 3e, 3g and 3h displayed moderate activity against α-amylase and/or α-glucosidase enzymes compared with the acarbose drug. The molecular docking study revealed that all active compounds displayed a different type of intermolecular interaction in the pocked site of these enzymes. Interestingly, in the Artemia salina assay, the compound 3d exhibited a higher cytotoxic effect than 5-fluorouracil. All these results support the pharmacological potential of quinazoline-2,4-diones since all evaluated compounds behave as moderate inhibitors of the enzymes α-amylase and/or α-glucosidase. Graphic abstract: An easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Moreover, the in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity are reported.[Figure not available: see fulltext.]
Synthesis, 2D-QSAR studies and biological evaluation of quinazoline derivatives as potent anti-trypanosoma cruzi agents
Battini, Leandro,Bollini, Mariela,Bruno, Ana M.,Casal, Juan J.,Lombardo, María E.,Ni?o, María E.,Puente, Vanesa R.,Sasiambarrena, Leandro D.,Valdez, Damián A. G.
, p. 265 - 276 (2019/07/12)
Background: Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives. Objective: The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy. Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes. Results: Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells. Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
High-selective HDAC6 inhibitor promotes HDAC6 degradation following autophagy modulation and enhanced antitumor immunity in glioblastoma
Liu, Jia-Rong,Yu, Chao-Wu,Hung, Pei-Yun,Hsin, Ling-Wei,Chern, Ji-Wang
, p. 458 - 471 (2019/03/23)
Glioblastoma is the most fatal type of primary brain cancer, and current treatments for glioblastoma are insufficient. HDAC6 is overexpressed in glioblastoma, and siRNA-mediated knockdown of HDAC6 inhibits glioma cell proliferation. Herein, we report a high-selective HDAC6 inhibitor, J22352, which has PROTAC (proteolysis-targeting chimeras)-like property resulted in both p62 accumulation and proteasomal degradation, leading to proteolysis of aberrantly overexpressed HDAC6 in glioblastoma. The consequences of decreased HDAC6 expression in response to J22352 decreased cell migration, increased autophagic cancer cell death and significant tumor growth inhibition. Notably, J22352 reduced the immunosuppressive activity of PD-L1, leading to the restoration of host anti-tumor activity. These results demonstrate that J22352 promotes HDAC6 degradation and induces anticancer effects by inhibiting autophagy and eliciting the antitumor immune response in glioblastoma. Therefore, this highly selective HDAC6 inhibitor can be considered a potential therapeutic for the treatment of glioblastoma and other cancers.
2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and application thereof
-
Paragraph 0051; 0055, (2018/04/21)
The invention belongs to the technical field of medicines and relates to 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone compounds and an application thereof. 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives comprise stereisomers and pharmaceutically applicable salts of the compounds and have the general structural formula shown in the description, wherein R is described inthe claims and description. The 2-[3-(4-morpholinyl)propylamine]-3-aryl-4-quinolinone derivatives and pharmaceutically applicable acid-added salts of the compounds can be combined with existing medicines or used separately to serve as influenza virus inhibitors to treat influenza and have better curative effects on various type-A influenza in particular.
Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate
Ismail, El Fekki,Ali, Ibrahim A.I.,Fathalla, Walid,Alsheikh, Amer A.,Tamney, El Said El
, p. 104 - 120 (2017/06/19)
A series of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate 10-13a-f has been developed on the basis of the N-chemoselective reaction of 3-substituted quinazoline-2,4-diones 3a-d with ethyl chloroacetate and azide coupling method with amino acid ester hydrochloride. The precursor quinazoline diones 3a-d chemoselective reactions were studied using DFT(B3LYP)/6-311G level of theory and were prepared by a new rearrangement method from the corresponding 2-(3-methyl-4-oxo-3,4- dihydroquinazolin-2-ylthio) acetohydrazide 6. {figure presented}.
Oxidative Rearrangement of Isatins with Arylamines Using H2O2 as Oxidant: A Facile Synthesis of Quinazoline-2,4-diones and Evaluation of Their Antibacterial Activity
Shi, Guanghao,He, Xinwei,Shang, Yongjia,Yang, Cheng,Xiang, Liwei
, p. 1835 - 1843 (2017/09/06)
A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed. The reaction features the mild reaction conditions, broad substrate scope, metal-free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate the antimicrobial activities towards two Gram-negative bacterial strains (Escherichia coli, and Klebsiella pneumonia) and two Gram-positive bacterial strains (Staphylococcus epidermidis, and Staphylococcus aureus) using the Broth microdilution method.
One-pot Syntheses of Some New 2,4(1H,3H)-quinazolinedione Derivatives in the Absence of Catalyst
Mohammadi, Ali Asghar
, p. 2075 - 2078 (2017/05/29)
A facile, rapid and one-pot procedure for the synthesis of some new 2,4(1H,3H)-quinazolinediones is described. The method involves the one-pot condensation of isatoic anhydride, primary amine and carbonyl diimidazole (CDI) in the absence of organic or inorganic catalyst. It affords the corresponding product in high yield.
Synthesis, molecular structure and spectroscopic studies of some new quinazolin-4(3H)-one derivatives; An account on the N- versus S-Alkylation
Hagar, Mohamed,Soliman, Saied M.,Ibid, Farahate,El Ashry, El Sayed H.
, p. 667 - 679 (2016/01/09)
A new series of N- and S-alkylated products of 3-aryl-1H,3H-quinazolin-2,4-dione and 3-aryl-2-mercapto-3H-quinazolin-4-one, respectively, were prepared in good yields via efficient nucleophilic substitution reaction of the SH and NH substrates with methyl
