- The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity
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Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC50 value of 0.46 and 0.50 μM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure–activity relationship analysis.
- Sepehri, Nima,Iraji, Aida,Yavari, Ali,Asgari, Mohammad Sadegh,Zamani, Saeed,Hosseini, Samanesadat,Bahadorikhalili, Saeed,Pirhadi, Somayeh,Larijani, Bagher,Khoshneviszadeh, Mahsima,Hamedifar, Halleh,Mahdavi, Mohammad,Khoshneviszadeh, Mehdi
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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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- Synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives using heteropolyacids as green, heterogeneous and recyclable catalysts
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Reaction of isatoic anhydride with aniline derivatives gave 2-amino-N-(aryl)benzamides. The latters reacted with phenylisothiocyanate in the presence of heteropolyacids in various solvents which afforded 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives. The effects of various heteropolyacids including Preyssler and Keggin on the yields and reaction times have been investigated.
- Allameh,Heravi,Hashemi,Bamoharram
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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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- Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Setected Green Chemistry Methods
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In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was porformed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride-urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16-76%), while microwave-induced synthesis showed lower effectiveness (13-49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by1H and13C NMR spectroscopy.
- Jerkovi?, Igor,Komar, Mario,Kraljevi?, Tatjana Gazivoda,Molnar, Maja
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- Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers
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Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Accordingly, new quinazoline-based derivatives having the structural features of VEGFR-2 inhibitors were designed and synthesized. Anti-proliferative activities were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Compounds 26b, 29a, 29b and 30 showed excellent anti-cancer activities against all cell lines. Moreover, compound 31 was the most active with IC 50 values of 3.97 ± 0.2, 4.83 ± 0.2 and 4.58 ± 0.3 μM, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities, compound 31 showed a high activity against VEGFR-2 with an IC50 value of 2.5 ± 0.04 μM, almost equal to that of sorafenib (IC50 = 2.4 ± 0.05 μM). Further studies revealed the ability of this promising quinazoline derivative 31 to induce apoptosis and arrest cell cycle growth at G2/M phase. In vivo antitumor activities of the synthesized compounds revealed that compounds 30 and 31 possessed significant tumor growth inhibition effect. Molecular docking studies were also performed and finally we can say that VEGFR-2 inhibition confers the reported cytotoxic activities.
- Belal, Amany,Eissa, Ibrahim H.,El-Gamal, Kamal M. A.,El-Sharkawy, Abdou,Elhendawy, Mostafa A.,Elsohly, Mahmoud A.,Ibrahim, Mohammed K.,Mahdy, Hazem A.,Mehany, Ahmed B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.
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- Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study
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Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC50 (μM) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC50 0.05 μM), diclofenac (IC50 0.8 μM) and indomethacin (IC50 0.49 μM) reference drugs. They also showed 15-LOX inhibition with IC50 (μM) 6.21, 4.33, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC50 2.41 μM) and Meclofenamate sodium (IC50 5.64 μM) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC50 values of 4.78 μM and 5.63 μM, respectively, compared to that of diclofenac sodium (4.86 μM). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC50 = 0.13 μM). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products.
- Moussa, Ghandoura,Alaaeddine, Rana,Alaeddine, Lynn M.,Nassra, Rasha,Belal, Ahmed S.F.,Ismail, Azza,El-Yazbi, Ahmed F.,Abdel-Ghany, Yasser S.,Hazzaa, Aly
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p. 635 - 650
(2018/01/02)
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- Identification of potent cholecystokinin-B receptor antagonists: Synthesis, molecular modeling and anti-cancer activity against pancreatic cancer cells
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Advanced malignant stages of pancreatic cancer have poor prognosis and very few treatment strategies are available. Pancreatic cancer is known to possess unique growth-related receptors that when activated, stimulate tumour proliferation. Gastrin and its related peptide cholecystokinin (CCK) are also significantly involved in the growth of this cancer type as well as other malignancies through activation of the cholecystokinin-B receptor (CCK-BR). New treatment strategies with CCK-BR antagonists are being suggested that suppress the growth promoting effects of gastrin. In this paper, we report the development of two series of quinazolinone derivatives incorporating hydrazinecarbothioamide (compounds 3a-g) and the hydrazino group (compounds 4a-e) as linkers for developing CCK-BR antagonists. The affinities of the compounds were determined using docking into the CCK-BR homology modeled structure. The compounds were tested for in vitro CCK-BR binding and gastric acid secretion in an isolated lumen-perfused mouse stomach assay. The compounds exhibited CCK-BR binding activity (IC50) in the range of 0.2-975 nM and showed good gastric acid secretion inhibitory activity. Molecular modeling of the compounds was done and pharmacophore mapping results showed good prediction of in vitro activity which correlated well with the experimental antagonistic activity. The compounds were further tested for their cytotoxicity on CCK-BR expressing pancreatic cancer cells. The results of the study provided two potent CCK-BR antagonists which also possess good to moderate growth inhibitory activities against pancreatic cancer cells.
- Kumari, Saroj,Chowdhury, Joyita,Sikka, Manisha,Verma, Priyanka,Jha, Prakash,Mishra, Anil K.,Saluja, Daman,Chopra, Madhu
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p. 1561 - 1574
(2017/07/25)
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- Synthesis and Anticonvulsant Activity Evaluation of 4-Phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one and Its Derivatives
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A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a-x) with triazole and other heterocyclic substituents (7-14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o > 25.5, PI6q > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline. A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones with triazole and other heterocyclic substituents were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity using maximal electroshock and rotarod neurotoxicity tests.
- Zhang, Hong-Jian,Jin, Peng,Wang, Shi-Ben,Li, Fu-Nan,Guan, Li-Ping,Quan, Zhe-Shan
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p. 564 - 574
(2015/08/06)
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- Microwave-assisted cyclocondensation for the synthesis of 3-Aryl-2-thioquinazolin-4(3h)-ones
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An efficient synthesis of 3-aryl-2-thioquinazolin-4(3H)-one 1a-f is given by the condensation of anthranilic acid and dithiocarbamate triethylammonium salts of substituted aniline in ethanol as solvent under microwave irradiation.
- Patil, Suresh,Jadhav,Shejwal,Deshmukh
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experimental part
p. 1858 - 1860
(2012/08/13)
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- Reactivity of cyanothioformamides and 3-(4-bromophenyl)-5-imino-4-oxazolidinethione toward ortho-substituted nucleophiles
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The substituted benzoazoles 4 and 5a,b were obtained by the reaction of cyanothioformamides 1d and 1b or 1c with o-substituted aromatic amines 2b and 2c, respectively. Fused pyrimidinones 10, 12, and 14 were synthesized by the reaction of oxazolidinethion
- El-Gaby, Mohamed S.A.,Ammar, Yousry A.,El-Sharief, Ahmed M.Sh.,Zahran, Medhat A.,Khames, Ahmed A.
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p. 611 - 616
(2007/10/03)
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- Synthesis of 3-Aryl-1H,3H-quinazolin-2,4-diones and Their 2-Thio Analogues
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3-Aryl-(2-thio)-1H,3H-quinazolin-2,4-diones (3, R= H, CH3, C2H5; X= O, S) have been obtained by the fusion of isatoic anhydrides (1, R= H, CH3, C2H5) with aryliso(thio)cyanates (2, X= O, S).
- Reddy, Ch. K.,Reddy, P. S. N.,Ratnam, C. V.
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p. 882 - 883
(2007/10/02)
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- Copper(II) Complexes of 3-N-Aryl Substitute Thioquinazolones
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CuII complexes and their pyridine adducts of 3-phenyl/p-tolyl/p-methoxyphenyl/p-ethoxyphenyl/p-chlorophenyl/p-bromophenyl-quinazoline-2-thione-4-one (HL) are prepared.Elemental analysis, magnetic and spectral data show that the copper complexes without pyridine have square-planar structure and the pyridine adducts have tetragonal structure.
- Dave, L. D.,Mathew, Cherian,Oommen, Varughese
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p. 273 - 275
(2007/10/02)
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