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4-(2-Chlorobenzyl)-1-(5-nitro-2-(pyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-a]quinazo-lin-5(4H)-one is a derivative of quinazolinones with antitumor, antibacterial, anti-inflammatory, and antimicrobial effects. Using diabetic jujube as a raw material, the title compound is synthesized by substitution and cyclization steps. The structure of the target compound is confirmed by FTIR, 1H and 13C NMR, and MS spectroscopies. The precise structure of the 4-(2-chlorobenzyl)-1-(5-nitro-2-(pyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one compound is analyzed by single crystal X-ray diffraction (XRD). The molecular structure is further calculated using density functional theory (DFT) and the result is compared with the XRD value. The molecular electrostatic potential and frontier molecular orbitals of the title compound are investigated using DFT. In addition, the obtained atomic coordinates for the single crystal of the compound are then applied in a molecular docking simulation, and the title compound is found to participate in a number of important binding interactions in the SHP2 binding sites. [ABSTRACT FROM AUTHOR]

A series of new quinazolinones and related compounds has been conveniently synthesized via reaction of (E)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(6-iodo-4-oxo-4H-benzo[d] [1,3] oxazin-2-yl)acrylonitrile (2) with different nitrogen nucleophiles. The structures of the prepared compounds were fully elucidated using IR, 1H-NMR, and 13C-NMR spectra. The newly synthesized compounds were tested in vitro against a panel of three human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, mammary gland breast MCF-7, and colon cancer HCT-116. Some of the tested compounds showed satisfactory activity. [ABSTRACT FROM AUTHOR]

In this investigation, novel g-C3N4/Cu3TiO4 (CNCT) nanocomposite was synthesized by using a simple thermal condensation method. The synthesized CNCT nanocomposite was characterized by X-ray Diffraction, Transmission electron microscopy, Atomic force microscopy, Energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, UV–vis diffuse reflectance spectroscopy, Photoluminescence, Brunauer–Emmett–Telle, Zeta Potential, and Thermogravimetric analysis. The study revealed that the catalysts prepared have high crystalline nature, optical light-absorbing property, high surface area, and stability. The CNCT- nanocomposite was found to be an extraordinary visible light absorbing catalyst for the synthesis of quinoxaline and quinazolinone derivatives, which have important benefits in a variety of drug applications. Quinoxaline and quinazolinones were prepared from anthranilamide, diamines, benzil, and corresponding aldehydes under Ultrasonic/visible light-medium with a notable amount of g-C3N4/Cu3TiO4. The results exhibit good and excellent yields of product derivatives at mild conditions under Ultrasonic/visible light-medium. Ultrasounds always clean the active site catalyst, promoting activity and reusability. Most notably, with preserved reactivities, this heterogeneous g-C3N4/Cu3TiO4 composite can be used atleast 5 times. Furthermore, we examined the reusability of the catalyst under Ultrasonication coupled with Visible light and in the absence of an Ultrasonication medium. Finally, advantages of the method are non-conventional approach, green solvent, reduced reaction duration, mild condition, and reusable catalyst. [ABSTRACT FROM AUTHOR]

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme. [ABSTRACT FROM AUTHOR]

Synthesis of new Schiff base derivatives bearing a 6-nitro-2-ibuprofenyl-4(3H)-quinazolin-4-one skeleton, as well as their in vitro biological evaluation as inhibitors of nitric oxide synthase (iNOS and nNOS) isoforms, is defined. Structures of these novel heterocycles were confirmed based on their spectral, (IR, 1H NMR, 13C NMR and MS) and elemental analyses. In general, the assayed compounds behave as better iNOS than nNOS inhibitors. Quinazolinyl Schiff bases 9a-e are the most active inhibitors of all tested compounds and the most iNOS/nNOS selective of all studied compounds, with expected potential as anti-stroke agents.

The current project deals with designing and synthesizing of colourimetric chemosensors to detect the cations in the aqueous medium and biological sample. To achieve this goal a new series of quinazolinone derivatives have been synthesized via reaction of the novel 6-nitro-2-propyl-4H-benzo[d][1,3]oxazin-4-one 3 with selected nitrogen nucleophiles, namely, formamide, hydrazine hydrate, hydroxylamine hydrochloride, o-phenylendiamine, o-aminophenol and oaminothiophenol, urea and/or thiourea. Structures of the new compounds have been investigated depending on their spectral data (IR, 1H and 13C NMR and MS) and elemental analyses. Some of the newly synthesized products exhibit significant response as chemosensors for a few cations detection. [ABSTRACT FROM AUTHOR]

A series of novel 1,2,4-triazolo[1,5-a]pyrimidine-containing quinazolin-4(3H)-one derivatives (8a–8o) were designed, synthesized and assessed for their in vitro antibacterial and antifungal activities in agriculture. All the title compounds were completely characterized via 1H NMR, 13C NMR, HRMS and IR spectroscopic data. In particular, the molecular structure of compound 8f was further corroborated through a single-crystal X-ray diffraction measurement. The turbidimetric method revealed that some of the compounds displayed noticeable bactericidal potencies against the tested plant pathogenic bacteria. For example, compounds 8m, 8n and 8o possessed higher antibacterial efficacies in vitro against Xanthomonas oryzae pv. oryzae with EC50 values of 69.0, 53.3 and 58.9 μg/mL, respectively, as compared with commercialized agrobactericide bismerthiazol (EC50 = 91.4 μg/mL). Additionally, compound 8m displayed an EC50 value of 71.5 μg/mL toward Xanthomonas axonopodis pv. citri, comparable to control bismerthiazol (EC50 = 60.5 μg/mL). A preliminary structure–activity relationship (SAR) analysis was also conducted, based on the antibacterial results. Finally, some compounds were also found to have a certain antifungal efficacy in vitro at the concentration of 50 μg/mL. [ABSTRACT FROM AUTHOR]

In this research, the synthesis of the quinazolinone derivatives by the reaction of diaminoglyoxime with anthranilic acid or methyl 2-amino benzoate over an acetic acid-functionalized magnetic silica-based catalyst in water was described. The acetic acid-functionalized catalyst was prepared using a three-step procedure from magnetite NPs that initially coated with a layer of silica through the sol–gel process, modified with an aminosilane layer and functionalized with bromoacetic acid. The catalyst was characterized by means of spectroscopic and microscopic techniques, and its activity was investigated for the synthesis of the quinazolinones, bisquinazolinone and oxadiazole quinazolinones obtained from diaminoglyoxime in water at room temperature. [ABSTRACT FROM AUTHOR]

• Design of hybrid analogues with indolyl oxoacetamide & quinazolinone scaffold synthesis and in vitro PL inhibitory screening of the synthesized analogues. • Enzyme kinetics study of the most potent analogue to check the type of inhibition. • Cytotoxic effect of the most potent analogue using the MTT assay. Pancreatic lipase (PL) is a key enzyme responsible for the digestion of dietary fat. Hence the inhibition of PL is an effective strategy for mitigating obesity. In this study, a novel series of 18 indolyl oxoacetamide–quinazolinone hybrid analogues (9a-h, 13aa-13fd) were designed, synthesized, and evaluated for PL inhibition activity. An approach of molecular hybridization was utilized by considering the PL inhibitory potential of indole, α-ketoamide, and quinazolinone scaffolds. A Propyl linker was attached for better binding at the PL active site, leading to enhanced PL inhibitory potential. Among all the synthesized analogues, 13be exhibited the highest PL inhibitory activity (IC 50 = 4.71 ± 0.851 μM) with a docking score of -147.06 kcal/mol. The activities of all the synthesized analogues were compared with the orlistat (IC 50 = 0.86 ± 0.090 µM). The most potent analogue, 13be revealed the competitive mode of enzyme inhibition with the K i value of 1.826 µM. The molecular docking and dynamics simulation analysis also revealed the strong binding of 13be at the active site of PL. Interestingly, the potent analogue 13be when tested on RAW 264.7 cell line using MTT assay, was found to be nontoxic at a concentration range of 1-20 µM. Therefore, the current work validates the effectiveness of the molecular hybridization approach for designing indolyl oxoacetamide–quinazolinone hybrids for inhibiting PL. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] A metal-free approach to the construction of novel spiro[ quinazoline - thiophen ]one framework via an acetic acid promoted formal [3 + 2] cycloaddition is developed. A library of functionalized spiro[quinazoline-thiophen](thi)ones were efficiently synthesized in good to excellent yields under mild conditions. The protocol features high atom-economy, an eco-benign catalyst and molecular diversity. [ABSTRACT FROM AUTHOR]

Dysregulation of the Wnt signaling pathway contributes to the development of many cancer types. Natural compounds produced with biotechnological systems have been the focus of research for being a new drug candidate both with unlimited resources and cost-effective production. In this study, it was aimed to reveal the effects of isopropylchaetominine on cytotoxic, cytostatic, apoptotic and Wnt signaling pathways in brain, pancreatic and prostate cancer. The IC 50 values of isopropylchaetominine in U-87 MG, PANC1, PC3 and LNCaP cells were calculated as 91.94 μM, 41.68 μM, 54.54 μM and 7.86 μM in 72nd h, respectively. The metabolite arrests the cell cycle in G 0 /G 1 phase in each cancer cells. Iso-propylchaetominine induced a 4.3-fold and 1.9-fold increase in apoptosis in PC3 and PANC1 cells, respectively. The toxicity of isopropylchaetominine in healthy fibroblast cells was assessed using the annexin V method, and no significant apoptotic activity was observed between the groups treated with the active substance and untreated. In U-87 MG, PANC1, PC3, and LNCaP cells under treatment with isopropylchaetominin, the expression levels of DKK3, TLE1, AES, DKK1, FRZB, DAB2, AXIN1/2, PPARD, SFRP4, APC and SOX1 7 tumor suppressor genes increased significantly. Decreases in expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5, Wnt6, Wnt10, Wnt11, FRZ2, FRZ3, FRZ7, TCF7L1, BCL9, PYGO, CCND2, c-MYC, WISP1 and CTNNB1 oncogenic genes were detected. All these result shows that isopropylchaetominine can present promising new treatment strategy in different cancer types. [Display omitted] • Iso-propylchaetominine exhibits anticancer activity in in vitro models of brain, pancreatic and prostate cancer. • Iso-propylchaetominin arrests the cell cycle in the G0/G1 phase. • Iso-propylchaetominine regulates the Wnt signaling pathway. • Iso-propylchaetominine causes cell cycle arrest by regulating the Wnt pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quinazolinone derivatives were designed keeping Ispinesib and Idelalisib as reference structures. • Compounds 3a, 3b, 3e, 3g and 3h revealed nanomolar potency against KSP and PI3Kδ. • Compounds were found to be active against MDA-MB-231 breast cancer cells. • Anticancer activity was found to be associated with their P53 -dependent apoptotic activity. Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC 50 of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC 50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of quinazolinone derivatives were synthesized and tested preliminarily for their in vitro AChE inhibitory activity. • Compounds 4b, 5a, 6f, 6 h, 7b were tested for their enhancing activity of cognitive function by Morris water maze test. • Compounds 4b, 5a, 6f, 6 h, 7b were tested for their in vivo brain and serum AChE inhibitory activities. • Selected compounds 4b, 5a, 6f, 6 h, 7b were tested for their in vivo anti inflammatory activity (anti TNF-α, NF-ĸB, IL-1β and IL-6 activity). • Selected compounds 4b, 5a, 6f, 6 h, 7b were tested for their in vivo anti-oxidant activity. • Histopathological examination was carried out to better explain the cortical and hippocampal changes in cerebral tissues. • Compounds 6f, 6h, 7b showed promising AChE enzyme inhibitory activity and anti-inflammatory activity. • Docking study illustrates the binding modes in AchE enzyme along with the reference compound (donepezil). Since Alzheimer disease is one of the most prevalent types of dementia with a high mortality and disability rate, so development of multi-target drugs becomes the major strategy for battling AD. This study shows the development of a series of quinazolinone based derivatives as novel, multifunctional anti-AD drugs that exhibit both cholinesterase inhibitory and anti-inflammatory properties. The preliminary results of the in vitro AChE inhibition activity showed that compounds 4b, 5a, 6f, 6 h and 7b were better represented for further evaluation. Furthermore, in-vivo AChE inhibition activity and behavior Morris water maze test against donepezil as reference drug were evaluated. Additionally, hippocampal inflammatory markers; TNF-α, NFĸB, IL-1β and IL-6 and antioxidant markers; SOD and MDA were assessed to evaluate the efficacy of quinazolinone derivatives against AD hallmarks. The results showed that 6f , 6 h and 7b have promising anti-acetylcholinesterase, anti-inflammatory and antioxidant activities thus, have a significant effect in treatment of AD. Moreover, Histopathological examination revealed that 6f, 6 h and 7b derivatives have neuroprotective effect against neuronal damage caused by induced scopolamine model in mice. Finally, the binding ability of the synthesized derivatives to the target, AChE was investigated through molecular docking which reflected significant interactions to the target based on their docking binding scores. Hence, the newly designed quinazolinone derivatives possess promising anti-acetylcholinesterase activity and challenging for the management of AD in the future. [ABSTRACT FROM AUTHOR]

Triazoles and quinazolinones are important heterocyclic structures with diverse biological properties including cytotoxic, antibacterial, antifungal and anticonvulsant activities. Due to valuable cytotoxic effects of both triazole and quinazoline derivatives, in this study a series of quinazolinone-triazole hybrids were synthesized in a multiple-step reaction procedure. 3-Amino-quinazolinone derivatives were treated with chloroacetyl chloride in the presence of dichloromethane/triethylamine to afford 2-chloro -N-(4-oxo-2- quinazolin3 (3H)-yl) acetamide derivatives. The reaction of resultants with 4-mehyl-4-H-1, 2, 4-triazole-3- thiol in dry acetone and potassium carbonate led to the formation of final products. Synthesized compounds were evaluated for their cytotoxic effects against MCF-7 and Hela cell lines using MTT colorimetric assay. Amongst tested compounds, 6a showed the highest cytotoxic activity against MCF7 cell line at all tested concentrations while compounds 6b and 6c indicated mild cytotoxic effects against Hela cell line at highest tested concentration reducing cell viability about 40%. The IC50 values of tested compounds revealed that the MCF-7 is more susceptible to the compound 6a.

1, 3, 4- Oxadiazoles and quinazolinones are privileged structures with extensive biological activities. On account of reported anticancer activity of them, in this study, a multi-step reaction procedure has been developed for the synthesis of some quinazolinone-1, 3, 4-oxadiazole derivatives. Reaction of the synthesized 3-amino-4(3H) quinazolinone derivatives with chloroacetyl chloride in the presence of dichloromethane/triethylamine yielded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives as intermediate. Treatment of the resultants with 5- (4-chlorophenyl) 1, 3, 4-oxadiazole-2-thiol in dry acetone and potassium carbonate gave coupled derivatives of quinazolinone-1, 3, 4-oxadiazole. The cytotoxic effect of final compounds was tested against MCF-7 and HeLa cell lines using MTT assay. Compound 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio) N-(4-oxo-2-propylquinazolin)3(4H)acatamide 6a exhibited remarkable cytotoxic activity at 10 and 100 μM against HeLa cell line. The alteration of substituents on C2 of quinazolinone ring revealed that the introduction of propyl moeity improved cytotoxic activity against HeLa cell line.

Chikungunya virus (CHIKV) has repeatedly spread via the bite of an infected mosquito and affected more than 100 countries. The disease poses threats to public health and the economy in the infected locations. Many efforts have been devoted to identifying compounds that could inhibit CHIKV. Unfortunately, successful clinical candidates have not been found yet. Computations through the simulating recognition process were performed on complexation of the nsP3 protein of CHIKV with the structures of triply conjugated drug lead candidates. The outcomes provided the aid on rational design of functionalized quinazoline-(α-substituted coumarin)-arylsulfonate compounds to inhibit CHIKV in Vero cells. The molecular docking studies showed a void space around the β carbon atom of coumarin when a substituent was attached at the α position. The formed vacancy offered a good chance for a Michael addition to take place owing to steric and electronic effects. The best conjugate containing a quinazolinone moiety exhibited potency with EC50 = 6.46 μM, low toxicity with CC50 = 59.7 μM, and the selective index (SI) = 9.24. Furthermore, the corresponding 4-anilinoquinazoline derivative improved the anti-CHIKV potency to EC50 = 3.84 μM, CC50 = 72.3 μM, and SI = 18.8. The conjugate with 4-anilinoquinazoline exhibited stronger binding affinity towards the macro domain than that with quinazolinone via hydrophobic and hydrogen bond interactions.

An efficient protocol for obtaining fused quinazolinones through an oxidative free-radical cyclization under metal- and tin-free conditions is described. The oxidative cyclization of various N -3-ω-iodoalkyl derivatives to provide tricyclic systems using dicumyl peroxide as the sole reagent is studied. The method then is employed for the syntheses of 5-, 6-, and 7-membered fused quinazolinone analogues, including the natural products deoxyvasicinone and mackinazolinone. A xanthate-based oxidative radical cascade addition/cyclization process that allows the production of new menthol- and testosterone-quinazolinone conjugates, as well as the first total synthesis of leucomidine C, are also reported. [ABSTRACT FROM AUTHOR]

In this study, a new benzopyrimidine analog was designed and synthesized by substituting 3-nitrophenyl ring and thiosemicarbazide nucleus at N-3 and C-2 positions of quinazoline ring, respectively. The title compounds, 1-substituted-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)isothioureas 7A – 7J were obtained via reactions of 2-hydrazino-3-(2-chlorophenyl)quinazolin-4(3H)-one (5) with different alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. All synthesized compounds were screened for their antitubercular, anti-HIV, and antibacterial activity against selected Gram-positive and Gram-negative bacteria using agar diffusion method. Amongst, compounds 2-methyl-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chloropheny)isothiourea (7I) and 2-methyl-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chlorophenyl)isothiourea (7F) showed the most potent activity against P. vulgaris and S. aureus with a MIC of 3 μg/mL. Compound 7I exhibited antitubercular activity at a minimum MIC of 3.125 μg/mL and anti-HIV activity at EC50 of 2.91 μg/mL against HIV1 and HIV2, thus offering probable lead for further development and optimization of new antitubercular and anti-HIV drugs. Results obtained in this study confirm that the synthesized and biologically evaluated benzopyrimidines possess promising antimicrobial, antitubercular, and anti-HIV properties and provide new scaffolds for antimicrobial activity. [ABSTRACT FROM AUTHOR]

Chiral 2‐alkylquinazolinones are key synthetic intermediates, but their preparation in high optical purity is challenging. Thus, a multicomponent procedure integrating anthranilic acids, N‐Boc‐amino acids, and amines in the presence of methanesulfonyl chloride, N‐methylimidazole, and copper(II) chloride was developed to mildly afford N‐Boc‐2‐alkylaminoquinazolin‐4(3H)‐ones with excellent preservation of enantiomeric purity (>99% ee). Copper(II) chloride was essential to retaining enantiopurity, and reaction component structural changes were well tolerated, resulting in an efficient, all‐in‐one procedure that promotes sequential coupling, lactonization, aminolysis, and cyclization in good yields. The method was applied to the rapid assembly of four key intermediates used in the synthesis of high profile quinazolinones, including several PI3K inhibitor drugs. [ABSTRACT FROM AUTHOR]

In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC50 values in the range of 45.3 ± 1.4 µM to 195.5 ± 4.7 µM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC50 = 45.3 ± 1.4 µM was around 17 times more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed. [ABSTRACT FROM AUTHOR]

A facile and general transition‐metal‐free access to 1‐substituted‐4‐quinazolinones 2 has been achieved based on the proline‐mediated cyclization of carbamoylbenzamides 1 in the presence of potassium t‐butoxides in DMSO at 100 °C within several hours. The gram‐scale synthesis of 1‐phenyl‐4‐quinazolinone 2 a has also been achieved without the loss of efficiency. The one‐pot synthesis of 1‐phenyl‐4‐quinazolinone 2 a has proven to be possible starting from 2‐bromobenzamide and phenylisocyanate in an acceptable yield. The present reactions were assumed to proceed through radical intermediates as the major path and also the SNAr route as a minor path based on several control experiments. [ABSTRACT FROM AUTHOR]

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K i values in the range of 19.28–135.88 nM for α-glycosidase (K i value for standard inhibitor = 187.71 nM), 0.68–23.01 nM for acetylcholinesterase (K i value for standard inhibitor = 53.31 nM), 1.01–29.56 nM for butyrylcholinesterase (K i value for standard inhibitor = 58.16 nM), 10.25–126.05 nM for human carbonic anhydrase I (K i value for standard inhibitor = 248.18 nM), and 13.46–178.35 nM for human carbonic anhydrase II (K i value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects. • Novel quinazolinone derivatives 7a-n were synthesized. • They evaluated against some metabolic enzymes. • Cytotoxicity study of the compounds 7a-n demonstrated. • Molecular docking was studied. [ABSTRACT FROM AUTHOR]

Currently available drugs being used to treat leishmaniasis have several shortcomings, including high toxicity, drug administration that requires hospitalization, and the emergence of parasite resistance against clinically used drugs. As a result, there is a dire need for the development of new antileishmanial drugs that are safe, affordable, and efficient. In this study, two new series of synthesized quinazolinone derivatives were investigated as potential future antileishmanial agents, by assessing their activities against the Leishmania (L.) donovani and L. major species. The cytotoxicity profiles of these derivatives were assessed in vitro on Vero cells. The compounds were found to be safer and without any toxic activities against mammalian cells, compared to the reference drug, halofuginone, a clinical derivative of febrifugine. However, they had demonstrated poor antileishmanial growth inhibition efficacies. The two compounds that had been found the most active were the mono quinazolinone 2d and the bisquinazolinone 5b with growth inhibitory efficacies of 35% and 29% for the L. major and L. donovani 9515 promastigotes, respectively. These outcomes had suggested structural redesign, inter alia the inclusion of polar groups on the quinazolinone ring, to potentially generate novel quinazolinone derivatives, endowed with effective antileishmanial potential. [ABSTRACT FROM AUTHOR]

Microwave irradiation (MWI), as a unique, effective, sustainable, more economic, and greener source of energy compared to conventional heating, is applied in different organic transformations to result in the rapid formation of desired compounds due to thermal/kinetic effects. In this review, we try to underscore the applications of microwave irradiation (MWI) in the synthesis of quinazoline and quinazolinone derivatives that have been achieved and reported on in the last two decades.

The cyclo condensation of some bi-functionally quinazolinones with some phosphorus dihalides in dry pyridine led to novel 1,3,4,2-oxadiazaphospholo[5,4-b]quinazolinones, 1,3,4,2-thiadiazaphospholo[5,4-b]quinazolinones and 1,2,4,3-triazaphospholo[5,1-b]quinazolinones. The structure of novel products was established by IR and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Multi-component reactions to form heterocyclic compounds possessing quinolone, benzothiazole or quinazolinone moieties are very well-known. Various derivatives of these molecules exhibit remarkable medicinal properties. Based on this fact, the present paper targets for the first time to synthesize a fused molecule containing all these three important heterocyclic units through a three-component one-pot synthesis via cyclocondensation reaction. The molecular iodine catalyzes this facile reaction of substituted-2-phenoxyquinoline-3-carbaldehyde (or) substituted-2-phenylthioquinoline-3-carbaldehyde, 2-aminobenzothiazole and 1,3-cyclohexanedione in ethanol to synthesize derivatives of 12-(2-oxo-1,2-dihydroquinolin-3-yl)-2,3,4,12-tetrahydro-1H-benzo[4,5]thiazolo[2,3-b] quinazolin-1-one with excellent yields. All the products isolated in pure form were characterized by spectroscopic as well as analytical data. The mechanism reveals that the reaction proceeds through intramolecular dehydration and further leads to the formation of an unexpected product from the quinoline attached phenoxy group to the corresponding ketone by the elimination of phenol/thiophenol molecule. The present methodology offers an eco-friendly synthetic route, excellent yields, mild reaction conditions, inexpensive catalyst, short reaction time and very easy work-up. [ABSTRACT FROM AUTHOR]

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Cancer is a broad classification of diseases that can affect any organ or body tissue due to aberrant cellular proliferation for unknown reasons. Many present chemotherapeutic drugs are highly toxic and have little selectivity. Additionally, they lead to the development of medication resistance. Therefore, developing tailored chemotherapeutic drugs with minimal side effects and good selectivity is crucial for cancer treatment. 2-(1 H )-Quinazolinone is one of the vital scaffold and anticancer activity is one of the prominent biological activities of this class. Here we report the novel set of amide-enriched 2-(1 H )-quinazolinone derivatives ( 7a-j ) and their apoptotic activity with the help of MTT assay method against four human cancer cell lines: PC3 (prostate cancer), DU-145 (prostate cancer), A549 (lung cancer), and MCF7 (breast cancer). When compared to etoposide, every synthetic test compound ( 7a-j ) exhibited moderate to excellent activity. The IC 50 values of the new amide derivatives ( 7a-j ) varied from 0.07 ± 0.0061 μM to 10.8 ± 0.69 μM. While the positive control, etoposide, exhibited 1.97 ± 0.45 μM to 3.08 ± 0.135 μM range. Among the novel amide derivatives ( 7a-j ), in particular, 7i and 7j showed strong apoptotic activity against MCF7; 7h showed against PC3, and 7g showed against DU-145. Molecular docking studies of test compounds ( 7a-j ) with the EGFR tyrosine kinase domain (PDB ID: 1M17) protein provided the significant docking scores for each test compound ( 7a-j ) (-9.00 to -9.67 kcal/mol). Additionally, DFT investigations and MD simulations validated the predictions of molecular docking. According to the findings of the ADME analysis, oral absorption by humans is anticipated to be higher than 85 % for all test compounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

To develop aryloxyphenoxypropionate herbicides with a novel structure and improved activity, a total of 39 aryloxyphenoxypropionate/amide derivatives containing quinazolinone moiety were synthesized and further bioevaluated. The bioassay results in the greenhouse showed that most of the target compounds had good herbicidal activity under postemergence conditions, of which, QPP-I-6 displayed excellent herbicidal activity against Echinochloa crusgalli , Digitaria sanguinalis , Spartina alterniflora , Eleusine indica, and Pennisetum alopecuroides with inhibition rates >90% at a dosage of 187.5 g ha -1 . More importantly, QPP-I-6 displayed higher crop safety to Gossypium hirsutum , Glycine max , and Arachis hypogaea than the commercial herbicide quizalofop- p -ethyl. Studying the molecular mode of action by phenotypic observation, membrane permeability evaluation, transcriptomic analysis, and in vivo ACCase activity evaluation reveals that QPP-I-6 is a novel ACCase inhibitor. The present work demonstrates that QPP-I-6 can serve as a lead compound for further developing novel ACCase-inhibiting herbicides.

The promising quinazolinone-based pyridine derivatives (4a-j) were synthesized and subsequently tested for their antimycobacterial activities against the various drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb) strains to combat infectious diseases and address growing concerns about the devastating effects of tuberculosis (TB). Utilizing 1 H NMR, 13 C NMR, and mass spectra, the structural and molecular confirmation of the synthesized compounds were deciphered. With minimum inhibitory concentration (MIC) values ranging from 0.31 to 19.13 μM, the results showed that compounds 4e and 4f showed promise anti-TB action against both drug-sensitive and drug-resistant TB strains. To study the cytotoxicity of synthesized molecules, normal Vero and mouse macrophage (RAW264.7) cell lines were utilized. Remarkably, it was revealed that at the highest concentration tested, none of the newly synthesized molecules were toxic to the Vero cell line. The binding patterns of the potent compounds 4b, 4e and 4f in the active site of the mycobacterial membrane protein Large 3 (MmpL3) protein are also revealed by molecular docking studies, which has contributed to the development of a structural rationale for Mtb inhibition. The physicochemical characteristics of the compounds were then predicted using theoretical calculations. Overall, the molecular docking results, physiochemical properties, and observed antimycobacterial activity all point to compound 4e with trifluoromethyl and compound 4f with nitro moiety as potential quinazolinone linked pyridine-based MmpL3 inhibitors.Communicated by Ramaswamy H. Sarma.

The production of penicillin-binding protein 2a (PBP2a), a cell wall synthesis protein, is primarily responsible for the high-level resistance observed in methicillin-resistant Staphylococcus aureus (MRSA). PBP2a exhibits a significantly reduced affinity for most β-lactam antibiotics owing to its tightly closed active site. Quinazolinones (QNE), a novel class of non-β-lactam antibiotics, could initiate the allosteric regulation of PBP2a, resulting in the opening of the initially closed active pocket. Based on our previous study, we have a basic understanding of the dual-site inhibitor ceftaroline (CFT) induced allosteric regulation of PBP2a. However, there are still limitations in the knowledge of how combining medicines, QNE and piperacillin (PIP), induce the allosteric response of PBP2a and inhibit its function. Herein, molecular dynamics (MD) simulations were performed to elucidate the intricate mechanisms underlying the combination mode of QNE and PIP. Our study successfully captured the opening process of the active pocket upon the binding of the QNE at the allosteric site, which alters the signaling pathways with a favorable transmission to the active site. Subsequent docking experiments with different conformational states of the active pocket indicated that all three inhibitors, PIP, QNE, and CFT, exhibited higher docking scores and more favorable docking poses to the open active pocket. These findings reveal the implied mechanism of QNE-mediated allostery underlying combination therapy and provide novel insights into developing innovative therapeutic modalities against MRSA.Communicated by Ramaswamy H. Sarma.

Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC 50  of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC 50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

6,7-Bis-(2-methoxyethoxy)-4(3H)-quinazolinone (BMEQ) was selected from quinazolinones for its strong tyrosinase inhibitory activity (IC 50  = 160 ± 6 μM). It suppressed tyrosinase activity in a competitive way and quenched the fluorescence of the enzyme through a static mechanism. The binding of BMEQ to tyrosinase increased the hydrophobicity of the latter and facilitated non-radiative energy transfer between them. The formation of BMEQ-tyrosinase complex was driven by hydrogen bonds and hydrophobic interactions, and it loosened the basic framework structure of tyrosinase, affecting the conformation of the enzyme, and leading to a decrease in tyrosinase activity. In addition, the BMEQ postponed the oxidation of phenolics and flavonoids by inhibiting polyphenol oxidase (PPO) and peroxidase (POD), which resulted in the inhibition of the browning of fresh-cut apples. This study identified a novel tyrosinase inhibitor BMEQ and verified its potential application for improving the preservation of postharvest fruits., (Copyright © 2023 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

A series of flavonol derivatives containing quinazolinone were designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results of the half maximal effective concentration (EC 50 ) test against TMV showed that the EC 50 value of curative activity of K5 was 139.6 μg/mL, which was better than that of the commercial drug ningnanmycin (NNM) 296.0 μg/mL, and the EC 50 value of protective activity of K5 was 120.6 μg/mL, which was superior to that of NNM 207.0 μg/mL. The interaction of K5 with TMV coat protein (TMV-CP) was investigated using microscale thermophoresis (MST) and molecular docking and the results showed that K5 can combine with TMV-CP more strongly to TMV-CP than that NNM can. Furthermore, the assay measuring malondialdehyde (MDA) content indicated that K5 had the ability to improve the disease resistance of tobacco. Hence, this study offers strong evidence that flavonol derivatives have potential as novel antiviral agents., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In this paper, a series of novel 3-methyl-quinazolinone derivatives was designed, synthesised and evaluated for antitumor activity in vitro on wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and three human cancer cell lines including A549, PC-3, and SMMC-7721. The results displayed that some of the compounds had good activities, especially 2-{4-[(3-Fluoro-phenylimino)-methyl]-phenoxymethyl}-3-methyl-3H-quinazolin-4-one (5 g), 2-{4-[(3,4-Difluoro-phenylimino)-methyl]-phenoxymethyl}-3-methyl-3H-quinazolin-4-one (5k) and 2-{4-[(3,5-Difluoro-phenylimino)-methyl]-phenoxymethyl}-3-methyl-3H-quinazolin-4-one (5 l) showed high antitumor activities against three cancer cell lines. Moreover, compound 5k could induce late apoptosis of A549 cells at high concentrations and arrest cell cycle of A549 cells in the G2/M phase at tested concentrations. Also, compound 5k could inhibit the EGFRwt-TK with IC50 value of 10 nM. Molecular docking data indicates that the compound 5k may exert inhibitory activity by forming stable hydrogen bonds with the R817, T830 amino acid residues and cation-Π interaction with the K72 residue of EGFRwt-TK. [ABSTRACT FROM AUTHOR]

Inhibitory action of newly synthesised 4-(2-(2-substituted-thio-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides compounds 2–13 against human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII, was evaluated. hCA I was efficiently inhibited by compounds 2–13 with inhibition constants (KIs) ranging from 57.8–740.2 nM. Compounds 2, 3, 4, and 12 showed inhibitory action against hCA II with KIs between 6.4 and 14.2 nM. CA IX exhibited significant sensitivity to inhibition by derivatives 2–13 with KI values ranging from 7.1 to 93.6 nM. Compounds 2, 3, 4, 8, 9, and 12 also exerted potent inhibitory action against hCA XII (KIs ranging from 3.1 to 20.2 nM). Molecular docking studies for the most potent compounds 2 and 3 were conducted to exhibit the binding mode towards hCA isoforms as a promising step for SAR analyses which showed similar interaction with co-crystallized ligands. As such, a subset of these mercaptoquinazolin-4(3H)-one compounds represented interesting leads for developing new efficient and selective carbonic anhydrase inhibitors (CAIs) for the management of a variety of diseases including glaucoma, epilepsy, arthritis and cancer. [ABSTRACT FROM AUTHOR]

Pd‐catalyzed decarboxylative ortho‐aroylation of 2‐aryl‐quinazolinones with α‐oxocarboxylic acids for the synthesis of diaryl ketones has been developed. Biologically interested novel quinazolinones with diaryl ketone functionality has been obtained with moderate to excellent yield from easily accessible 2‐aryl‐quinazolinones having inherent directing group. [ABSTRACT FROM AUTHOR]

Two series of quinazolinone derived Schiff's bases were synthesized and characterized by analytical and spectroscopic techniques. All the compounds were screened for their in vitro biological studies. The in vitro antioxidant activities of these compounds were evaluated employing 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline-6-sufonic acid) (ABTS+) and N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD+) radical assay. The results revealed that compounds 31 (IC50: 35 μg/mL) and 32 (IC50: 40 μg/mL) showed excellent antioxidant activity and their IC50 is lower than the IC50 of standards such as butylated hydroxyl anisole, ascorbic acid and gallic acid in all the three performed assays. In anti-inflammatory activity, compounds 7–26 (IC50: 10-35 μg/mL) showed extraordinary activity compared to standards indomethacin (IC50: 40 μg/mL) and ibuprofen (IC50: 65 μg/mL). In antimicrobial activity, compounds 25–42 shows potent antibacterial activity and compounds 25–42 shows potent antifungal activity compared to standards streptomycin (ZoI: 10 mm) and bavistin (ZoI:10 mm) respectively. To study the structure activity relationship (SAR), electron donating groups (-OH and -OCH3) favors the antioxidant activity, electron withdrawing groups (F, Cl, Br and -NO2) favors the anti-inflammatory activity, and both electron donating (-OH and -OCH3) and electron withdrawing (F, Cl, Br and -NO2) groups (25–32) or heterocyclic moiety (33–42) favors antimicrobial activity.

Quinazolinone and quinazoline have been shown different pharmacological activities, namely anticancer, anti-inflammatory, anti-hyperlipidemia, analgesic, antihypertensive, and antibacterial. On the other hand, molecular hybridization is a structural modification technique in the design of new ligands which consist of two or more pharmacologically active molecules in one structure. Therefore, due to the importance of the biological activities of quinazolinones for the development of new therapeutic agents, this review emphasizes current findings on various quinazolinone-based hybrids in medicinal chemistry. Moreover, it highlights the biological activities and structure-activity relationship of these hybrids.

Abstract An efficient, simple protocol has been established for convenient synthesis of novel 2,3-disubstituted thieno[2,3-d]pyrimidin-4(3H)-one derivatives in good to high yields through a one-pot, two-step and three-component reaction from 2H-thieno[2,3-d][1,3]oxazine-2,4(1H)-diones, aromatic aldehydes, and amines.

Nitrogen-rich heterocyclic compounds represent a unique class of chemicals with especial properties and have been modified to design novel pharmaceutically active compounds. In this study, a series of novel quinazolinone derivatives with substituted quinoxalindione were synthesized in two parts. In the first part, 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione was prepared from para-amino -m-crozol in 5 steps. In the next part, 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives were obtained from antranilic acid. Then reaction of 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione with 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives resulted in the production of final componds. The structures of synthesized compounds were confirmed by IR and 1H-NMR. Cytotoxic activity of the compounds were evaluated at 0.1, 1, 10, 50 and 100 μM concentrations against MCF-7 and HeLa cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Almost all new compounds showed cytotoxic activity in both cell lines. Among tested compounds, 11g displayed the highest cytotoxic activity against both cell lines.

Novel benzosuberone-quinazolinones hybrids have been synthesized efficiently in high yields, and their structures have been confirmed by1H and 13C NMR, ESI-MS, and HRMS spectra. According to the in vitro tests of products for their antiproliferative activity against HeLa, MDA-MB-231, A549, and MIAPACA cancer cell lines, the compound 9b demonstrates significant cytotoxicity against A549 with GI50 value 0.4 µM and compound 8a exhibits activity against MIAPACA with GI50 value 0.6 µM. [ABSTRACT FROM AUTHOR]

In this study, quinazolinone derivatives have been synthesized via a suitable and efficient procedure by one‐potmulti‐component reactions of 3‐amino‐1,2,4‐triazole or 2‐aminobenzimidazole, dimedone and aromatic aldehydes in the presence of Fe3O4@TiO2‐IL as nanocatalyst under solvent‐free condition. The products were prepared in good to excellent yields using Fe3O4@TiO2‐IL magnetic nanocatalyst. The Fe3O4@TiO2 magnetic nanoparticles (MNPs) were prepared using beet juice extract and functionalized with IL based on DABCO. Moreover, the core‐shell structured magnetic Fe3O4@TiO2‐IL has been characterized by different techniques such as 1H‐NMR, FT‐IR, VSM, XRD, SEM, TGA, TEM and EDX. To the best of our knowledge, the prepared ionic liquid displayed a good protective and activator agent for magnetic nanocatalyst. [ABSTRACT FROM AUTHOR]

A series of novel 2-(4-nitrophenyl)-3-(R-benzothiazol-2-yl)quinazolin-4(3H)-ones 4a–4g (R = Alk, AlkO, Hal, NO2) were synthesized from the corresponding substituted 2-aminobenzothiazoles and 2-(4-nitrophenyl)-4H-3,1-benzoxazin-4-one via a nucleophilic addition reaction. The structures of the novel compounds were assigned on the basis of the elemental analyses and FTIR, 1H NMR, and mass spectra. The synthesized compounds were tested for anticonvulsant, antimicrobial, and antioxidant activities. All the compounds increased the seizure latency compared to control. Compound 4b (R = 6-NO2) exhibited significant anticonvulsant activity, comparable to that of the standard drug Phenytoin. Antimicrobial activity testing revealed moderate to good activity in all the test compounds, and 4a (R = H) and 4b compared in activity with the standard drug Chloramphenicol. The antioxidant activity of compounds 4a, 4d (R = 5-Br), and 4f (R = 4,6-Me2) (IC50 39.30, 15.55, and 42.95 µg/mL, respectively) was found to be higher compared to the standard drug ascorbic acid (IC50 48.30 µg/mL). [ABSTRACT FROM AUTHOR]

In this research, a novel strategy for synthesis of quinazolinones has been formulated via one pot condensation of aromatic aldehydes, isatoic anhydride, and aniline by employing prepared povidone‐phosphotungstic acid (PVP‐PWA) hybrid as a novel solid acid heterogenous catalyst in methanol at 80 °C. The synthesized PVP‐PWA is confirmed by FTIR, XRD and studied for TGA, BET plots. The reaction is optimized for different solvents and loading of catalyst. The yields of all quinazolinone derivatives are observed in the range of 78–86%. All the synthesized quinazolinones are investigated by spectral data. The use of ecologically benign catalyst, good atom economy, environmental affordability, and easy work up makes this protocol sustainable. [ABSTRACT FROM AUTHOR]

An efficient and rapid one‐pot synthesis of quinazolinone via a three‐component carbonylative coupling of 2‐aminobenzamide or 2‐aminobenzonitrile, Mo(CO)6 and aryl bromides has been developed recently. This method provide a new way to synthesize quinazolinone which has a wide substrate scope, good functional group tolerance and mild reaction condition. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: A facile approach to chiral dihydroquinazolinone derivatives has been described via biomimetic asymmetric reduction of quinazolinones with chiral and regenerable NAD(P)H models. The utility of this method was demonstrated by a concise synthesis of the bromodomain protein divalent inhibitor. [ABSTRACT FROM AUTHOR]

Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1–19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii–mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii. [ABSTRACT FROM AUTHOR]

Supporting information for this article is given via a link at the end of the document. By intercepting the acylpalladium species with C=N bond of azaarenes or imines other than free amines or alcohols, the difunctionalization of C=N bond was established via palladium‐catalyzed carbonylation/nucleophilic addition sequence. This method is compatible with a diverse range of azaarenes and imines and allows for the efficient synthesis of a wide range of quinazolinones and derivatives. The synthetic utility has been demonstrated by one‐step synthesis of evodiamine and its analogue with inexpensive starting materials. [ABSTRACT FROM AUTHOR]