- Design, synthesis, biological evaluation, and molecular docking study of thioxo-2,3-dihydroquinazolinone derivative as tyrosinase inhibitors
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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.
- 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
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- Design, synthesis, in vitro and in silico biological assays of new quinazolinone-2-thio-metronidazole derivatives
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A new series of quinazolinone-2-thio-metronidazole derivatives 9a-o was designed, synthesized and assayed for their activities against metabolic enzymes human carbonic anhydrase I and II (hCAs I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against CA enzymes, 4-fluorophenyl derivative 9i, was 4 and 7-times more potent than standard inhibitor acetazolamide against hCA I and II, respectively; 4-fluorobenzyl derivative 9m as the most potent compound against cholinesterase enzymes, was around 11 and 21-times more potent than standard inhibitor tacrine against AChE and BChE, respectively; the most active α-glucosidase inhibitor 9h with 4-methoxyphenyl moiety was 5-times more active that acarbose as standard inhibitor. Furthermore, in order to study interaction modes of the most potent compounds in the active site of their related enzymes, molecular modeling was performed. Druglikeness, ADME, and toxicity profile of the compounds 9i, 9m, and 9h were also predicted.
- Ansari, Samira,Asgari, Mohammad Sadegh,Biglar, Mahmood,Esfahani, Ensieh Nasli,Hamedifar, Haleh,Larijani, Bagher,Mahdavi, Mohammad,Mohammadi-Khanaposhtani, Maryam,Rastegar, Hossein,Tas, Recep,Taslimi, Parham
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- Novel quinazolin–sulfonamid derivatives: synthesis, characterization, biological evaluation, and molecular docking studies
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In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin–sulfonamid derivatives (9a–m) were synthesized, characterized and evaluated for their in vitro antidiabetic, anticholinergics, and antiepileptic activity. These synthesized novel quinazolin–sulfonamid derivatives (9a–m) were found to be effective inhibitor molecules for the α-glycosidase, human carbonic anhydrase I and II (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzyme, with Ki values in the range of 100.62 ± 13.68–327.94 ± 58.21 nM for α-glycosidase, 1.03 ± 0.11–14.87 ± 2.63 nM for hCA I, 1.83 ± 0.24–15.86 ± 2.57 nM for hCA II, 30.12 ± 3.81–102.16 ± 13.87 nM for BChE, and 26.16 ± 3.63–88.52 ± 20.11 nM for AChE, respectively. In the last step, molecular docking calculations were made to compare biological activities of molecules against enzymes which are achethylcholinesterase, butyrylcholinesterase and α-glycosidase. Communicated by Ramaswamy H. Sarma.
- Sepehri, Nima,Mohammadi-Khanaposhtani, Maryam,Asemanipoor, Nafise,Hosseini, Samanesadat,Biglar, Mahmood,Larijani, Bagher,Mahdavi, Mohammad,Hamedifar, Haleh,Taslimi, Parham,Sadeghian, Nastaran,Norizadehtazehkand, Mostafa,Gulcin, Ilhami
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- A green and efficient synthesis of 2-thioxoquinazolinone derivatives in water using potassium thiocyanate
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Green chemistry is one of the most important routes for the synthesis of heterocyclic compounds. In this regard, the synthesis of 2-thioxoquinazolinone derivatives was achieved by condensation of versatile materials including isatoic anhydride, amine and potassium thiocyanate in the green medium of water. This convenient and ef?cient method affords the desired products with good to excellent yields.
- Rezanejade Bardajee, Ghasem,Ghaedi, Aseyeh,Hekmat, Shohreh,Abarashi, Ghazale,Mahdavi, Mohammad,Akbarzadeh, Tahmineh
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p. 519 - 529
(2017/09/27)
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- Practical approach to 2-thioxo-2,3-dihydroquinazolin-4(1H)-one via dithiocarbamate–anthranilic acid reaction
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A practical and straightforward protocol has been developed for the preparation of 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives from dithiocarbamate chemistry. The method involves the reaction of anthranilic acid derivatives (2-aminobenzoic acid, 2-aminobenzamide and isatoic anhydride) with various dithiocarbamate derivatives using ethanol as solvent. The main advantages of this protocol include practical simplicity, good to high yields, and ease of product isolation, purification and cheapness of the solvent.
- Azizi, Najmedin,Edrisi, Mahtab
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p. 109 - 112
(2017/01/13)
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- Nanomagnetically modified polyphosphoric acid (NiFe2O4@SiO2-PPA): An efficient, fast, and reusable catalyst for the synthesis of 2-thioxoquinazolinones under solvent-free conditions
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Polyphosphoric acid functionalized silica-coated magnetic nanoparticles with core-shell structure (NiFe2O4@SiO2-PPA) has been used as a magnetically recyclable green catalyst for the one-pot three-component synthesis of 2-thioxoquinazolinones by the reaction of isatoic anhydride, primary amines and thiourea under neat conditions. The catalyst is readily recovered by simple magnetic decantation and can be recycled five times with no significant loss of catalytic activity.
- Eshghi, Hossein,Khojastehnezhad, Amir,Moeinpour, Farid,Bakavoli, Mehdi,Zeinabi, Nafiseh,Allameh, Sadegh
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p. 7915 - 7924
(2015/04/16)
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- Convenient and sequential one-pot route for synthesis of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives
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A new and efficient synthetic process has been developed for preparation of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives. The related products were synthesized through reaction of isatoic anhydride, amines/anthranilic acids, and carbon disulfide (CS2) in the presence of potassium hydroxide in ethanol at reflux. Graphical abstract: [Figure not available: see fulltext.]
- Asadi, Mehdi,Masoomi, Shiva,Ebrahimi, Seyed Mostafa,Mahdavi, Mohammad,Saeedi, Mina,Shafiee, Abbas,Foroumadi, Alireza
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p. 497 - 504
(2014/03/21)
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- Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma
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In this study, a novel series of quinazolinone derivatives analogue to nitraquazone structure were synthesized. The compounds tested for their inhibitory activity against phosphodiesterase 4B revealed that compound 6d shows promising inhibitory activity comparable to that of Rolipram, whereas compounds 6a and 6c exhibited moderate inhibitory activity. Springer Science+Business Media, LLC 2011.
- Elansary, Afaf K.,Kadry, Hanan H.,Ahmed, Eman M.,Sonousi, Amr Sayed Motawi
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p. 3327 - 3335
(2013/02/23)
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- An efficient one-pot multicomponent synthesis of 2,3-dihydro-3-alkyl/aryl- 2-thioxoquinazolin-4(1 H)-ones under solvent-free conditions
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A series of 2,3-dihydro-3-alkyl/aryl-2-thioxoquinazolin-4(1H)-one is prepared by one-pot multicomponent reaction of anthranilic acid, S,S-dimethyl trithiocarbonate and aliphatic/aromatic amine under solvent-free conditions. Georg Thieme Verlag Stuttgart New York.
- Devi, Nepram Sushuma,Singh, Sarangthem Joychandra,Singh, Okram Mukherjee
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p. 2111 - 2115
(2012/11/07)
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- One-pot synthesis of 2,3-dihydro-2-thioxoquinazolin-4(1H)-ones from nitro-compounds with the aid of tin(II) chloride
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(Chemical Equation Presented) A facile synthetic method using SnCl 2·2H2O system to promote the novel reductive cyclization of 2-nitrobenzamides and isothiocyanates is described. Sequentially, a series of 2,3-dihydro-2-thioxoquinazolin-4(1H)-ones were synthesized in good yields.
- Wang, Man-Man,Dou, Guo-Lan,Shi, Da-Qing
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experimental part
p. 939 - 943
(2010/09/03)
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- Synthesis and enantioselective cleavage of chiralic quinazoline carboxylic acid esters
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The synthesis of chiralic propionic acid ethylesters of 3-alkyl-4-oxo- 2-thioxo-1,2,3,4-tetrahydroquinazolines was described and their chromatographic behaviour was investigated on the chiralic phases (S,S)- Whelk-01 and Chiralcel-OD-H. The enantioselective cleavage succeeded by means of lipase of Candida cylindracea (CCL, E.C. 3.1.1.3.), of pork liver esterase (PLE, E.C. 3.1.1.1.) and of the enzymes of screening set Chirazyme, too. The results pointed out that the modification at the C3-alkyl group has a significant influence to the cleavage rate and the enantioselectivity. The highest selectivity is to obtain in presence of π-electrons in the 3- substituent whereas voluminous aryl groups block up the effectiveness of the enzymes used.
- Beyrich, Thorsten,Theiss
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p. 853 - 858
(2007/10/03)
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- 2-thio-organotin-4(3H)-quinazolinone
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Compounds of the formula: STR1 wherein X is independently halogen, lower alkyl of 1 to 6 carbon atoms, lower alkoxy of 1 to 6 carbon atoms, nitro, lower alkylsulfinyl of 1 to 6 carbon atoms, lower alkylthio of 1 to 6 carbon atoms, amino or trifluoromethyl; n is 0, 1, 2 or 3; R is hydrogen, alkyl of 1 to 10 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, lower alkenyl of 2 to 6 carbon atoms, or lower alkynyl of 2 to 6 carbon atoms, all optionally substituted with 1 to 3 of the same or different halogen atoms; or aryl of 6 to 12 carbon atoms; or substituted aryl substituted with 1 to 3 substituents independently selected from lower alkyl of 1 to 4 carbon atoms, lower alkoxy of 1 to 4 carbon atoms, and the group --S(O)k R2 where k is 0, 1 or 2 and R2 is lower alkyl of 1 to 4 carbon atoms, nitro, cyano or halogen; and R1 is lower alkyl of 1 to 6 carbon atoms, lower cycloalkyl of 3 to 8 carbon atoms or aryl of 6 to 12 carbon atoms, provided that R and R1 are not both cyclohexyl, are fungicidal and in some cases insecticidal.
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- A FACILE PREPARATION OF 3-SUBSTITUTED 2-THIOXO-TETRAHYDROQUINAZOLIN-4-ONES BY THE REACTION OF ANTHRANILAMIDE WITH ISOTHIOCYANATES
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3-Substituted 2-thioxo-tetrahydroquinazolin-4-ones (4a-d) can be synthesized in a convenient procedure directly by a treatment of anthranilamide with isothiocyanates at room temperature.However, anthranilamide was reacted with 4-isothiocyanato-1-benzylpiperidine (2e) leading to the formation of 2-thioureidobenzamide (3e) which was subsequently cyclized to 4e under a basic condition.
- Chan, Chao-Han,Shish, Fang-Jy,Liu, Kang-Chien,Chern, Ji-Wang
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p. 3193 - 3196
(2007/10/02)
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