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Abstract Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.

N-substituted 2-cyclopropyl-3-R-quinazoline-4()-ones [R: NH2 (1), N=CH(2-hydroxyphenyl) (2)] and Ni(II) chelate compound of 2-cyclopropyl-3-[(Z)-(2-hydroxybenzylidene)amino]quinazoline-4(3H)-one (3) were synthesized and their structures and properties were characterized using X-ray diffraction data, computational optimization, 1H and 13C NMR, IR spectroscopy, and diffuse reflectance spectra. Compounds 1 and 2 are monoclinic (space group P21/n). Unit cell parameters (a, b, c) are 9.2529; 4.7246; 22.3460 Å and 10.2811; 4.6959; 30.972 Å for 1 and 2, respectively. Nickel(II) chelate compound crystallizes in an orthorhombic crystal system (space group Pbca). Unit cell parameters (a, b, c) for 3 are 26.5010; 14.8791; 8.904975 Å, respectively. Schiff base 2 in the crystalline state exhibits two rotary isomers in a molar ratio of 1:3, among which only a minor component as a bidentate ligand can form compound 3 with Ni(II) ion. Nickel(II) ion in 3 is coordinated by N donor atoms and deprotonated O atoms of Schiff base ligands to form square-planar chelate node NiN2O2. All synthesized compounds revealed high antifungal activity against bread mold (Mucor mucedo). [ABSTRACT FROM AUTHOR]

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight. [ABSTRACT FROM AUTHOR]

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial-mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.

Introduction: The combination of BRAF and tyrosine kinase (TK) inhibitors has been demonstrated to be highly effective in inhibiting tumor development and is an approach for overcoming resistance in clinical trials. Accordingly, a novel series of 1,2,4-oxadiazole/quinazoline-4-one hybrids was developed as antiproliferative multitargeted inhibitors. Methods: The structures of the newly synthesized compounds 9a-o were validated using IR, NMR, MS, and elemental techniques. 9a-o were tested as antiproliferative agents. Results and Discussion: The results showed that the majority of the tested compounds showed significant antiproliferative action with 9b, 9c, 9h, 9k, and 9l being the most potent. Compounds 9b, 9c, 9h, 9k, and 9l were tested as EGFR and BRAF[sup V600E] inhibitors. These in vitro tests revealed that compounds 9b, 9c, and 9h are strong antiproliferative agents that may act as dual EGFR/BRAF[sup V600E] inhibitors. 9b, 9c, and 9h were further investigated for their inhibitory effect on mutant EGFR (EGFR[sup T790M]), and the results showed that the tested compounds had considerable inhibitory action. Cell cycle study and apoptosis detection demonstrated that compound 9b exhibits cell cycle arrest at the G2/M transition. Molecular docking simulations reveal the binding mechanism of the most active antiproliferative agents. [ABSTRACT FROM AUTHOR]

To develop aryloxyphenoxypropionate herbicides with novel structure and improved activity, a total of twenty-eight novel quinazolinone–phenoxypropionate derivatives containing a diester moiety were designed and synthesized. The herbicidal bioassay results in the greenhouse showed that QPEP-I-4 exhibited excellent herbicidal activity against E. crusgalli, D. sanguinalis, S. alterniflora, E. indica, and P. alopecuroides with inhibition rates >80% at a dosage of 150 g ha−1 and displayed higher crop safety to G. hirsutum, G. max, and A. hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying the herbicidal mechanism by phenotypic observation, membrane permeability evaluation, and transcriptomic analysis revealed that a growth inhibition of plants by QPPE-I-4 was the result from damage of the plants' biomembrane. The evaluation of ACCase activity in vivo indicated that QPPE-I-4 could inhibit ACCase and may be a new type of ACCase inhibitor. The present work indicated that QPPE-I-4 could represent a lead compound for further developing novel AOPP herbicides. [ABSTRACT FROM AUTHOR]

A set of twelve new quinazoline arylidene/heteroarylidene motifs have been synthesized by forming Schiff bases from the 3-amino-8-methyl-2-(p-tolyl)quinazolin-4(3H)-one intermediate. These compounds have been analyzed and tested for their anti-inflammatory and antimicrobial potential. The in vitro results for anti-inflammatory activity show that compound 6g (2-Br) exhibits the most potent activity with an inhibition of 96.89±0.83 against the standard medication. Compound 6d (4-OH) has the second-highest anti-inflammatory inhibition of 92.64±0.38. In terms of antimicrobial activity, compound 6d shows the highest inhibitory impact ranging from 12.5 to 50 µg/mL against specific bacterial and fungal pathogens. Compound 6g also demonstrates good action against E. coli, Klebsiella sp., B. megaterium, S. aureus, and A. niger species. Compounds 6e, 6j and 6k have strong antibacterial activity but only modest antifungal efficacy in antimicrobial activity tests. According to the SAR study, compounds 6d, 6e and 6k that have EDGs such as hydroxyl at the ortho, meta and para positions have both potent antimicrobial and anti-inflammatory activities. Moreover, compounds 6c, 6g, and 6j which have EWGs (-Cl, -Br, and -NO2) in the ortho and para positions exhibit better anti-inflammatory activity as compared to the meta-derivative 6b. Further evaluation of compounds 6d and 6g with standard antibiotics is crucial for treating harmful microorganisms. [ABSTRACT FROM AUTHOR]

Benzoxazine and quinazoline are nitrogen-containing heterocyclic scaffolds found in various biologically active compounds. Due to their diverse biological actions, these heterocyclic rings serve as crucial frameworks for designing medicinal compounds. This study aimed to synthesize and assess in vivo anti-inflammatory, analgesic, and low ulcerogenic potential of a few novel benz[d][1,3]-oxazin-4-one and quinazolinone derivatives. Benzoxazinones (3a-e) were synthesized by cyclizing the carboxylic group (-COOH) of five nonsteroidal anti-inflammatory drugs viz., aceclofenac, ibuprofen, diclofenac, mefenamic acid and ketoprofen (2a-e) with anthranilic acid (1) using dry phosphorus oxychloride (POCl3) in pyridine. The corresponding quinazolinone derivatives (5a-e) were obtained by reacting 3a-e with isonicotinic acid hydrazide (4). Both sets of compounds were evaluated for their anti-inflammatory, analgesic effects, and ulcerogenicity in animal models. Structural characterization was performed using spectral analysis. Among the benzoxazinone derivatives, compound 2-(2-((2,6-dichlorophenyl) amino) benzyl)-4H-benzo[d][1,3]oxazin-4-one (3d) exhibited significant anti-inflammatory activity (62.61% inhibition of rat paw edema) and analgesic activity (62.36% protection in acetic acid-induced writhings) with tolerable gastrointestinal toxicity (2.67 ulcerogenicity index) compared to quinazolinone derivatives. The results of anti-inflammatory and analgesic activities of both the series are comparable with the respective, positive control. Compound 3d, a benzoxazinone-diclofenac hybrid, emerged as a lead molecule with potent anti-inflammatory, analgesic activities and moderate gastric toxicity showcasing the promising potential for further development.

A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher's method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day. [ABSTRACT FROM AUTHOR]

Abstract In this pared, an efficient method is introduced for the synthesis of 3-alkyl-2-(((4-(2-oxopropyl)-1H-1,2,3-triazol-1-yl)alkyl)thio)-2,3-dihydroquinazolin-4(1H)-one derivatives. These novel products have both 1,2,3-triazole and quinazolinone in their structures. For the synthesis of these products, a novel catalyst is designed, synthesized, and characterized by the immobilization of copper onto modified magnetic iron oxide. The catalyst (denoted: Cu@Py-Oxa@SPION) was characterized by several characterization techniques. In this regard, 16 3-alkyl-2-(((4-(2-oxopropyl)-1H-1,2,3-triazol-1-yl)alkyl)thio)-2,3-dihydroquinazolin-4(1H)-one derivatives were synthesized in high isolated yields (77–86%). As an advantage, the catalyst is highly recoverable and its activity has not decreased after 7 sequential runs. The method is very efficient for the synthesis of the products in high isolated yields under mild reaction conditions in a green solvent. The scope of the method is broad and several examples were successfully synthesized using starting materials with different functional groups.

6,7-Bis-(2-methoxyethoxy)-4(3 H)-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. [Display omitted] [ABSTRACT FROM AUTHOR]

New methods have been developed for the synthesis of the substituted quinolines and quinazolinones derivatives by utilizing N-(2-aminobenzoyl)benzotriazoles under mild reaction conditions. 3-Acyl-2-alkyl(aryl)-4-hydroxyquinolines were obtained in modarete yields by the reaction of N-(2-aminobenzoyl)benzotriazoles and diketones in the presence of tert-BuOK. 3-Acylamino-4(3H) quinazolinones were obtained in good yields via N-(2-aminobenzoyl)benzotriazoles, orthoester and hyrazides in one-pot. [ABSTRACT FROM AUTHOR]

Benzoxazine and quinazoline are nitrogen-containing heterocyclic scaffolds found in various biologically active compounds. Due to their diverse biological actions, these heterocyclic rings serve as crucial frameworks for designing medicinal compounds. This study aimed to synthesize and assess in vivo anti-inflammatory, analgesic, and low ulcerogenic potential of a few novel benz[d][1,3]-oxazine-4-one and quinazolinone derivatives. Benzoxazinones (3a-e) were synthesized by cyclizing the carboxylic group (-COOH) of five nonsteroidal anti-inflammatory drugs viz., aceclofenac, ibuprofen, diclofenac, mefenamic acid and ketoprofen (2a-e) with anthranilic acid (1) using dry phosphorus oxychloride (POCl3 ) in pyridine. The corresponding quinazolinone derivatives (5a-e) were obtained by reacting 3a-e with isonicotinic acid hydrazide (4). Both sets of compounds were evaluated for their anti-inflammatory, analgesic effects, and ulcerogenicity in animal models. Structural characterization was performed using spectral analysis. Among the benzoxazinone derivatives, compound 2-(2-((2,6-dichlorophenyl) amino) benzyl)-4H-benzo[d][1,3]oxazin-4-one (3d) exhibited significant anti-inflammatory activity (62.61% inhibition of rat paw edema) and analgesic activity (62.36% protection in acetic acid-induced writhings) with tolerable gastrointestinal toxicity (2.67 ulcerogenicity index) compared to quinazolinone derivatives. The results of antiinflammatory and analgesic activities of both the series are comparable with the respective, positive control. Compound 3d, a benzoxazinone-diclofenac hybrid, emerged as a lead molecule with potent anti-inflammatory, analgesic activities and moderate gastric toxicity showcasing the promising potential for further development. [ABSTRACT FROM AUTHOR]

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 IC50 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 IC50 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.

A series of new quinazolinone derivatives (5a-l) were designed as 3CL protease inhibitors for SARS-CoV-2 infection. The designed derivatives were efficiently synthesized by S-alkylation/arylation of an intermediate, 6-fluoro-3-(4-fluorophenyl)-2-mercaptoquinazolin-4(3H)-one and their successful synthesis was established by analytical methods, viz. IR, 1H NMR, & 13C NMR spectroscopy. The in silico inhibitory potential against 3CLpro of SARS-CoV-2 were studied by means of docking and dynamics simulations, and compared with the co-crystallized ligand (VR4) of SARS-CoV-2 3CLpro. The compounds interacted strongly within the active catalytic dyad (Cys-His) site, thereby anticipated to obstruct the function of 3CLpro of SARS-CoV-2. Compounds 5b, 5c, 5i, 5j and 5l showed efficient binding with protease 3CLpro with XP Gscore of −7.4, −8.3, −7.8, −7.5 and −8.2 respectively. Furthermore, molecular dynamic simulation study of these compounds (5b, 5c, 5i, 5j and 5 l) showed stable interaction over 50 ns production run. Swiss ADME and pkCSM web tools showed favorable physicochemical and pharmacokinetic properties and fulfilled the criteria for drug-likeness of these selected studied compounds. The toxicity determination of these selected compounds predicted that some compounds were hepatotoxic, but were not AMES toxic. Compounds 5b, 5c, 5i, 5j and 5 l revealed their inhibitory potential against the SARS-CoV-2 3CLpro, and their IC50 values were attained at 1.58, 1.25, 1.97, 0.44 and 2.56 µM, respectively. In addition, these compounds were found to have devoid of any significant cytotoxicity even at a higher concentration of 20 µM against VeroE6 cells. These quinazolinone derivatives showed potent binding and inhibitory potential against SARS-CoV-2 3CLpro and may emerge as compounds that might act as prospective inhibitors.

In this pared, an efficient method is introduced for the synthesis of 3-alkyl-2-(((4-(2-oxopropyl)-1H-1,2,3-triazol-1-yl)alkyl)thio)-2,3-dihydroquinazolin-4(1H)-one derivatives. These novel products have both 1,2,3-triazole and quinazolinone in their structures. For the synthesis of these products, a novel catalyst is designed, synthesized, and characterized by the immobilization of copper onto modified magnetic iron oxide. The catalyst (denoted: Cu@Py-Oxa@SPION) was characterized by several characterization techniques. In this regard, 16 3-alkyl-2-(((4-(2-oxopropyl)-1H-1,2,3-triazol-1-yl)alkyl)thio)-2,3-dihydroquinazolin-4(1H)-one derivatives were synthesized in high isolated yields (77–86%). As an advantage, the catalyst is highly recoverable and its activity has not decreased after 7 sequential runs. The method is very efficient for the synthesis of the products in high isolated yields under mild reaction conditions in a green solvent. The scope of the method is broad and several examples were successfully synthesized using starting materials with different functional groups. [ABSTRACT FROM AUTHOR]

Natural products are a very rich source for obtaining new compounds with therapeutic potential. In the search for new antiparasitic and antimicrobial agents, molecular hybrids were designed based on the structures of antimicrobial marine quinazolinones and eugenol, a natural phenolic compound. Following reports of the therapeutic potential of quinazolinones and eugenol derivatives, it was expected that the union of these pharmacophores could generate biologically relevant substances. The designed compounds were obtained by classical synthetic procedures and were characterized by routine spectrometric techniques. Nine intermediates and final products were then evaluated in vitro against Trypanosoma brucei and Leishmania infantum. Antifungal and antibacterial activity were also evaluated. Six compounds (9b, 9c, 9d, 10b, 10c, and 14) showed mild activity against T. brucei with IC50 in the range of 11.17–31.68 μM. Additionally, intermediate 9c showed anti-Leishmania activity (IC50 7.54 μM) and was six times less cytotoxic against THP-1 cells. In conclusion, novel derivatives with a simple quinazolinone scaffold showing selectivity against parasites without antibacterial and antifungal activities were disclosed, paving the way for new antitrypanosomal agents. [ABSTRACT FROM AUTHOR]

The chemical constituents quinazolinone and piperazine hold significant importance in the realm of organic compounds due to their diverse range of biological and therapeutic attributes. In an effort to investigate the possible uses of these molecules, a team of scientists synthesized a unique set of chemical substances that combined piperazine and quinazolinone structures. This research involved a comprehensive investigation into the antimicrobial properties of a set of derivatives bearing the chemical structure N-(4-oxo-2-(4-(4-(2-(Substituted phenylamino) acetyl) piperazin-1-yl) phenyl) quinazolin-3(4H)-yl) benzamide, which was successfully synthesized with high yields. The synthesized compounds were carefully characterized using a range of physical methods, including mass spectrometry, FTIR, and 1H NMR spectroscopy, in addition to physical methods such as melting point measurement and thin-layer chromatography. Subsequently, using the agar well diffusion method, these compounds were evaluated for their antibacterial activity against a panel of microbial strains, including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The antifungal assay was also conducted against Candida albicans using the same approach. The broth microdilution technique was also used to establish the minimal inhibitory concentration. The synthesized compounds demonstrated impressive antifungal and antibacterial properties against every tested microbe. Notably, among the compounds evaluated, PRP7A6, PRP7A8, and PRP7A11 displayed the most potent antimicrobial effects against the pathogenic strains. [ABSTRACT FROM AUTHOR]

Oxidative stress, COX-2, LDHA and hyperglycemia are interlinked contributing pathways in the etiology, progression and metastasis of colon cancer. Additionally, dysregulated apoptosis in cells with genetic alternations leads to their progression in malignant transformation. Therefore, quinazolinones 3a–3h and 5a–5h were synthesized and evaluated as antioxidants, enzymes inhibitors and cytotoxic agents against LoVo and HCT-116 cells. Moreover, the most active cytotoxic derivatives were evaluated as apoptosis inducers. The results indicated that 3a, 3g and 5a were efficiently scavenged DPPH radicals with lowered IC50 values (mM) ranging from 0.165 ± 0.0057 to 0.191 ± 0.0099, as compared to 0.245 ± 0.0257 by BHT. Derivatives 3h, 5a and 5h were recognized as more potent dual inhibitors than quercetin against α-amylase and α-glucosidase, in addition to 3a, 3c, 3f and 5b–5f against α-amylase. Although none of the compounds demonstrated a higher efficiency than the reference inhibitors against COX-2 and LDHA, 3a and 3g were identified as the most active derivatives. Molecular docking studies were used to elucidate the binding affinities and binding interactions between the inhibitors and their target proteins. Compounds 3a and 3f showed cytotoxic activities, with IC50 values (µM) of 294.32 ± 8.41 and 383.5 ± 8.99 (LoVo), as well as 298.05 ± 13.26 and 323.59 ± 3.00 (HCT-116). The cytotoxicity mechanism of 3a and 3f could be attributed to the modulation of apoptosis regulators (Bax and Bcl-2), the activation of intrinsic and extrinsic apoptosis pathways via the upregulation of initiator caspases-8 and -9 as well as executioner caspase-3, and the arrest of LoVo and HCT-116 cell cycles in the G2/M and G1 phases, respectively. Lastly, the physicochemical, medicinal chemistry and ADMET properties of all compounds were predicted. [ABSTRACT FROM AUTHOR]

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In search of potent inhibitors of cholinesterase enzymes and antioxidant agents, synthetic derivatives of dihydroquinazolin-4(1H)-one (1–38) were evaluated as potential anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions and radical (DPPH and ABTS) scavenging activities. The structure–activity relationship (SAR) was mainly based on the different substituents at the aryl part which showed a significant effect on the inhibitory potential of enzymes and radical scavenging activities. The kinetic studies of most active compounds showed a noncompetitive mode of inhibition for AChE and a competitive mode of inhibition for the BChE enzyme. Additionally, molecular modelling studies were carried out to investigate the possible binding interactions of quinazolinone derivatives with the active site of both enzymes.

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 μM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (PA), one of the ESKAPE pathogens, is an opportunistic Gram-negative bacterium responsible for nosocomial infections in humans but also for infections in patients affected by AIDS, cancer, or cystic fibrosis (CF). Treatment of PA infections in CF patients is a global healthcare problem due to the ability of PA to gain antibiotic tolerance through biofilm formation. Anti-virulence compounds represent a promising approach as adjuvant therapy, which could reduce or eliminate the pathogenicity of PA without impacting its growth. Pyocyanin is one of the virulence factors whose production is modulated by the Pseudomonas quinolone signal (PQS) through its receptor PqsR. Different PqsR modulators have been synthesized over the years, highlighting this new powerful therapeutic strategy. Based on the promising structure of quinazolin-4(3H)-one, we developed compounds 7a–d, 8a,b, 9, 10, and 11a–f able to reduce biofilm formation and the production of virulence factors (pyocyanin and pyoverdine) at 50 µM in two PA strains responsible for CF acute and chronic infections. The developed compounds did not reduce the cell viability of IB3-1 bronchial CF cells, and computational studies confirmed the potential ability of novel compounds to act as potential Pqs system modulators. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 disease originated in China by the end of 2019 and has spread all over the world, with many casualties reported since then. Research for the discovery of effective pharmaceuticals is going on around the world. Pharmaceutical scientists are keenly interested in revealing the capacities of a large number of already existing molecules in molecular and drug databases to fight against coronavirus. We identified several triazole and quinazolinone derivatives from molecular databases that share key pharmacophore features with oxadiazole, a known drug-like compound, and conducted computational analysis to evaluate their ability to bind with the envelope protein of Severe Acute Respiratory Syndrome Coronavirus 2. The molecules were screened for their absorption, distribution, metabolism, excretion properties and drug-likeness using the SwissADME webserver. Out of a large number of molecules investigated, six were reported in this work that showed appreciable binding energy values. In vitro, in vivo toxicological studies and clinical trials have to be conducted to get the complete picture of their efficiency and toxicity. [ABSTRACT FROM AUTHOR]

In this paper, four new compounds with quinazolinone structure were designed and synthesized based on the special biological activity of quinazolinone. The four new compounds containing quinazolinone structures were synthesized using a one-pot method after intramolecular cyclization and dehydration catalyzed by aqueous methylamine solution. Their structures were characterized using 1H NMR, 13C NMR, FT-IR, and HRMS, and the crystal structure of 2a was characterized using X-ray diffraction. In their potential antifungal activity tests, it was found that the four newly synthesized compounds exhibited significant antifungal activity against all seven phytopathogenic fungi at concentrations of 150 and 300 mg/L. Among them, the target compound 2c showed the best inhibitory effect against Fusarium oxysporum f. sp. Niveum fungus, with 62.42% inhibition at a concentration of 300 mg/L. Compound 2c is expected to be a leading compound for the treatment of watermelon Fusarium wilt in the future, which is worth further study. [ABSTRACT FROM AUTHOR]

The treatment of many bacterial diseases remains a significant problem due to the increasing antibiotic resistance of their infectious agents. Among others, this is related to Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) and Mycobacterium tuberculosis. In the present article, we report on antibacterial compounds with activity against both S. aureus and MRSA. A straightforward approach to 2-(1H-indol-3-yl)quinazolin-4(3H)-one and their analogues was developed. Their structural and functional relationships were also considered. The antimicrobial activity of the synthesized compounds against Mycobacterium tuberculosis H37Rv, S. aureus ATCC 25923, MRSA ATCC 43300, Candida albicans ATCC 10231, and their role in the inhibition of the biofilm formation of S. aureus were reported. 2-(5-Iodo-1H-indol-3-yl)quinazolin-4(3H)-one (3k) showed a low minimum inhibitory concentration (MIC) of 0.98 μg/mL against MRSA. The synthesized compounds were assessed via molecular docking for their ability to bind long RSH (RelA/SpoT homolog) proteins using mycobacterial and streptococcal (p)ppGpp synthetase structures as models. The cytotoxic activity of some synthesized compounds was studied. Compounds 3c, f, g, k, r, and 3z displayed significant antiproliferative activities against all the cancer cell lines tested. Indolylquinazolinones 3b, 3e, and 3g showed a preferential suppression of the growth of rapidly dividing A549 cells compared to slower growing fibroblasts of non-tumor etiology. [ABSTRACT FROM AUTHOR]

A major active constituent of Moringa oleifera Lam. is 4-[(α-L-rhamnose oxy) benzyl] isothiocyanate (MITC). To broaden MITC's application and improve its biological activity, we synthesized a series of MITC quinazolinone derivatives and evaluated their anticancer activity. The anticancer effects and mechanisms of the compound with the most potent anticancer activity were investigated further. Among 16 MITC quinazolinone derivatives which were analyzed, MITC-12 significantly inhibited the growth of U251, A375, A431, HCT-116, HeLa, and MDA-MB-231 cells. MITC-12 significantly inhibited U251 cell proliferation in a time- and dose-dependent manner and decreased the number of EdU-positive cells, but was not toxic to normal human gastric mucosal cells (GES-1). Further, MITC-12 induced apoptosis of U251 cells, and increased caspase-3 expression levels and the Bax:Bcl-2 ratio. In addition, MITC-12 significantly decreased the proportion of U251 cells in the G1 phase and increased it in S and G2 phases. Transcriptome sequencing showed that MITC-12 had a significant regulatory effect on pathways regulating the cell cycle. Further, MITC-12 significantly decreased the expression levels of the cell cycle-related proteins CDK2, cyclinD1, and cyclinE, and increased those of cyclinA2, as well as the p-JNK:JNK ratio. These results indicate that MITC-12 inhibits U251 cell proliferation by inducing apoptosis and cell cycle arrest, activating JNK, and regulating cell cycle-associated proteins. MITC-12 has potential for use in the prevention and treatment of glioma. [ABSTRACT FROM AUTHOR]

The present study focuses on the synthesis of some 2-methoxyphenylquinazolin-4-one incorporated chalcone hybrids to evaluate their cytotoxic potential by MTT assay, and their affinity to bind with T790M mutated epidermal growth factor receptor (EGFR; protein data bank Id: 5Y9T) and G12D mutated Kirsten rat sarcoma (K-RAS; protein data bank Id:4EPT) by molecular docking (auto dock-4) by employing validated docking parameters. Against the lung cancer cells (A549), except C7 (IC50: 48.22 μg/ml), the other title compounds exhibited more cytotoxicity (IC50 16.88 μg/ml to 33.98 μg/ml) than the erlotinib (reference). Against the colorectal cancer cells, the compound C4 (IC50: 9.74 μg/ml) exhibited more cytotoxicity than the reference (IC50: 16.13 μg/ml). For the normal cell lines (Vero), the compound C1 (IC50 27.88 μg/ml) is less toxic to normal cells, than the reference. The title compounds can be a boon for the development of smart anticancer drugs with dual target virtue. [ABSTRACT FROM AUTHOR]

As bacteria continue to develop resistance mechanisms against antimicrobials, an alternative method to tackle this global concern must be developed. As the pqs system is the most well-known and responsible for biofilm and pyocyanin production, quinazolinone inhibitors of the pqs system in P. aeruginosa were developed. Molecular docking following a rationalised medicinal chemistry approach was adopted to design these analogues. An analysis of docking data suggested that compound 6b could bind with the key residues in the ligand binding domain of PqsR in a similar fashion to the known antagonist M64. The modification of cyclic groups at the 3-position of the quinazolinone core, the introduction of a halogen at the aromatic core and the modification of the terminal group with aromatic and aliphatic chains were investigated to guide the synthesis of a library of 16 quinazolinone analogues. All quinazolinone analogues were tested in vitro for pqs inhibition, with the most active compounds 6b and 6e being tested for biofilm and growth inhibition in P. aeruginosa (PAO1). Compound 6b displayed the highest pqs inhibitory activity (73.4%, 72.1% and 53.7% at 100, 50 and 25 µM, respectively) with no bacterial growth inhibition. However, compounds 6b and 6e only inhibited biofilm formation by 10% and 5%, respectively. [ABSTRACT FROM AUTHOR]

Quinazoline and quinazolinone derivatives display an extensive application in organic and pharmaceutical chemistry, and they have been used as natural and synthetic materials for medicinal chemistry purposes. Here I reported an investigation of a new series of quinazolinone ring derivatives. In this context, starting from the methyl anthranilate, six quinazolinone derivatives (4a-f) with various aminomethyl moieties at position 2 were synthesized (89-80%). The structures of compounds 4a-f were identified using FTIR and NMR Spectroscopy (1H NMR - 13C NMR). The data obtained from the all spectra clearly identify the structures of the compounds.

Reactions of 4H-3,1-benzoxazin-4-one 3 with various nitrogen nucleophiles; sodium azide, hydroxylamine hydrochloride, ammonium acetate, and formamide afforded new N-heterocyclic compounds 4-7. The synthesized quinazolinone derivative 7 was used as a useful building block for further synthesis of new series of N3-functionalized quinazolinone compounds 8-12. The chemical structures of all synthesized heterocyclic compounds were deduced from their spectroscopic analyses. The antimicrobial activity of the new compounds was evaluated against several pathogenic microorganisms, and most of them showed remarkable activity comparable to the antibacterial Ciprofloxacin and antifungal Clotrimazole.

In this study, 32 novel quinazolinone-scaffold-containing pyrazole carbamide derivatives were designed and synthesized in a search for a novel fungicide against Rhizoctonia solani. Single-crystal X-ray diffraction of 3-(difluoromethyl)-N-(2-((6,7-difluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a11) confirmed the structure of the target compounds. The in vitro antifungal activity of the target compounds against R. solani was evaluated at 100 µg/mL. The structure–activity relationship analysis results revealed that antifungal activity was highest when the substitution activity was at position 6. Moreover, the position and number of chlorine atoms directly affected the antifungal activity. Further in vitro bioassays revealed that 6a16 (EC50 = 9.06 mg/L) had excellent antifungal activity against R. solani that was higher than that of the commercial fungicide fluconazole (EC50 = 12.29 mg/L) but lower than that of bixafen (EC50 = 0.34 mg/L). Scanning electron microscopy), 7.33 (SEM) revealed that N-(2-((6,8-dichloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a16) also affected the mycelial morphology. The findings revealed that molecular hybridization was an effective tool for designing antifungal candidates. Meanwhile, pyrazolecarbamide derivatives bearing a quinazolinone fragment exhibited potential antifungal activity against R. solani.

Bacterial infections caused by methicillin-resistant Staphylococcus aureus have seriously threatened public health. There is an urgent need to propose an existing regimen to overcome multidrug resistance of MRSA. A unique class of novel anti-MRSA thiazolylketenyl quinazolinones (TQs) and their analogs were developed. Some synthesized compounds showed good bacteriostatic potency. Especially TQ 4 was found to exhibit excellent inhibition against MRSA with a low MIC of 0.5 μg/mL, which was 8-fold more effective than norfloxacin. The combination of TQ 4 with cefdinir showed stronger antibacterial potency. Further investigation revealed that TQ 4, with low hemolytic toxicity and low drug resistance, was not only able to inhibit biofilm formation but also could reduce MRSA metabolic activity and showed good drug-likeness. Mechanistic explorations revealed that TQ 4 could cause leakage of proteins by disrupting membrane integrity and block DNA replication by intercalated DNA. Furthermore, the synergistic antibacterial effect with cefdinir might be attributed to TQ 4 with the ability to induce PBP2a allosteric regulation of MRSA and further trigger the opening of the active site to promote the binding of cefdinir to the active site, thus inhibiting the expression of PBP2a, thereby overcoming MRSA resistance and significantly enhancing the anti-MRSA activity of cefdinir. A new strategy provided by these findings was that TQ 4, possessing both excellent anti-MRSA activity and allosteric effect of PBP2a, merited further development as a novel class of antibacterial agents to overcome increasingly severe MRSA infections. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) is a toxic, hazardous gas that has a colorless and odorless nature. On the other hand, CO possesses some physiological roles as a signaling molecule that regulates neurotransmitters in addition to its hazardous effects. Because of the dual nature of CO, there is a need to develop a sensitive, selective, and rapid method for its detection. Herein, we designed and synthesized a turn-on fluorescence probe, 2-(2′-nitrophenyl)-4(3H)-quinazolinone (NPQ), for the detection of CO. NPQ provided a turn-on fluorescence response to CO and the fluorescence intensity at 500 nm was increased with increasing the concentration of CO. This fluorescence enhancement could be attributed to the conversion of the nitro group of NPQ to an amino group by the reducing ability of CO. The fluorescence assay for CO using NPQ as a reagent was confirmed to have a good linear relationship in the range of 1.0 to 50 µM with an excellent correlation coefficient (r) of 0.997 and good sensitivity down to a limit of detection at 0.73 µM (20 ppb) defined as mean blank+3SD. Finally, we successfully applied NPQ to the preparation of a test paper that can detect CO generated from charcoal combustion. [ABSTRACT FROM AUTHOR]

Abstract Background Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a–e and dihydroquinazolinone 10a–f compounds were designed, synthesized as cytotoxic agents. Methodology All derivatives (5a–e and 10a–f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software. Results and discussion Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87–205.9 μM against HCT-116 cell line and 14.70–98.45 μM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 μM after 72 h, respectively, indicated the plausible activities of the synthesized compounds. Conclusion The compounds quinazolinone 5a–e and dihydroquinazolinone 10a–f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.

This research presents the synthesis of new quinazolinone-based Mannich bases in good yields via a three-step procedure. The first step is the reaction of 6-hydroxyanthranilic acid 1 with an excess of acetic anhydride at 150°C for 2 h to afford benzoxazinone 2 in 87% yield. Compound 2 is then reacted with 4-aminophenol in DMSO at reflux for 7 h to give compound 3 in 75% yield. Finally, the reaction of 3 with paraformadehyde and secondary amines in ethanol affords new quinazolinone-based Mannich bases 4a-c and 5a-e in 55-70% yields. The structure of Mannich bases have been characterized by NMR and MS spectra. The bio-assay results show that some new Mannich bases exhibited weak to moderate cytotoxic activity against SKLu-1 and MCF-7 cell lines. [ABSTRACT FROM AUTHOR]

Twenty 1,4-pentadiene-3-one derivatives containing quinazolinone (W1–W20) were designed and synthesized. The bioactivity test results showed that some compounds had antifungal activities in vitro. W12 showed excellent bioactivity against Sclerotinia sclerotiorum (S. sclerotiorum) and Phomopsis sp., with EC50 values of 0.70 and 3.84 μg/mL, which are higher than those of the control drug azoxystrobin at 8.15 and 17.25 μg/mL. In vivo activity tests were carried out on oilseed rape and kiwifruit. The protective effect of W12 on oilseed rape infected with S. sclerotiorum (91.7 and 87.3%) was better than that of azoxystrobin (90.2 and 79.8%) at 100 and 50 μg/mL, respectively, and the protective effect on kiwifruit infected with Phomopsis sp. (96.2%) was better than that of azoxystrobin (94.6%) at 200 μg/mL. Scanning electron microscopy results showed the hyphae of S. sclerotiorum treated with compound W12 abnormally collapsed and shriveled, inhibiting the growth of mycelium and, thus, laying the inhibiting effect on S. sclerotiorum. The results of the mechanism research showed that the action of W12 changed the mycelial morphology of S. sclerotiorum, affected the permeability of cells, increased the leakage of cytoplasm and allowed the cell membrane to break down. This study shows that 1,4-pentadiene-3-one derivatives containing quinazolinone have good effects on plant fungi and the potential for becoming new fungicides. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2-Mpro) plays an essential role in viral replication, transcription, maturation, and entry into host cells. Furthermore, its cleavage specificity for viruses, but not humans, makes it a promising drug target for the treatment of coronavirus disease 2019 (COVID-19). In this study, a fragment-based strategy including potential antiviral quinazolinone moiety and glutamine- or glutamate-derived peptidomimetic backbone and positioned nitro functional groups was used to synthesize putative Mpro inhibitors. Two compounds, G1 and G4, exhibited anti-Mpro enzymatic activity in a dose-dependent manner, with the calculated IC50 values of 22.47 ± 8.93 μM and 24.04 ± 0.67 μM, respectively. The bio-layer interferometer measured real-time binding. The dissociation kinetics of G1/Mpro and G4/Mpro also showed similar equilibrium dissociation constants (KD) of 2.60 × 10−5 M and 2.55 × 10−5 M, respectively, but exhibited distinct association/dissociation curves. Molecular docking of the two compounds revealed a similar binding cavity to the well-known Mpro inhibitor GC376, supporting a structure−function relationship. These findings may open a new avenue for developing new scaffolds for Mpro inhibition and advance anti-coronavirus drug research. [ABSTRACT FROM AUTHOR]

We synthesised a new series of sulphonamide-bearing quinazolinone derivatives 5-18 and evaluated their in vitro cytotoxicity in various cancer cell lines (A549, HepG-2, LoVo and MCF-7) and in normal human cells (HUVEC). Compounds 6 and 10 exhibited the higher activity against all the cancer cell lines compared with 5-flourourcil as positive control. The ability of the most promising compounds 6 and 10 to induce cell cycle arrest and apoptosis in breast cancer (MCF-7) cells was evaluated by flow cytometry. Reverse transcriptase-polymerase chain reaction and western blotting were used to evaluate the expression of apoptosis-related markers. We found that the 2-tolylthioacetamide derivative 6 and the 3-ethyl phenyl thioacetamide derivative 10 exhibited cytotoxic activity comparable to that of 5-fluorouracil as reference drug in MCF-7 and LoVo colon cancer cells. Cell cycle analysis showed a concentration-dependent accumulation of cells in the sub-G1 phase upon treatment with both compounds. The Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that the compounds 6 and 10 increased the early and late apoptosis cell death modes in a dose-dependent manner. These compounds downregulated the expression of B-cell lymphoma-2 (Bcl-2), while increasing that of p53, Bcl-2-like protein 4, and caspase-7, at the mRNA and protein levels. Molecular docking of compounds 6 and 10 with Bcl-2 predicted them to show moderate − high binding affinity (6: −7.5 kcal/mol, 10: −7.9 kcal/mol) and interactions with key central substrate cavity residues. Overall, compounds 6 and 10 were found to be promising anticancer and apoptosis-inducing agents.

Natural products are a very rich source for obtaining new compounds with therapeutic potential. In the search for new antiparasitic and antimicrobial agents, molecular hybrids were designed based on the structures of antimicrobial marine quinazolinones and eugenol, a natural phenolic compound. Following reports of the therapeutic potential of quinazolinones and eugenol derivatives, it was expected that the union of these pharmacophores could generate biologically relevant substances. The designed compounds were obtained by classical synthetic procedures and were characterized by routine spectrometric techniques. Nine intermediates and final products were then evaluated in vitro against Trypanosoma brucei and Leishmania infantum. Antifungal and antibacterial activity were also evaluated. Six compounds (9b, 9c, 9d, 10b, 10c, and 14) showed mild activity against T. brucei with IC50 in the range of 11.17–31.68 μM. Additionally, intermediate 9c showed anti-Leishmania activity (IC50 7.54 μM) and was six times less cytotoxic against THP-1 cells. In conclusion, novel derivatives with a simple quinazolinone scaffold showing selectivity against parasites without antibacterial and antifungal activities were disclosed, paving the way for new antitrypanosomal agents.

A green chemistry method was applied in the synthesis of N2,N6-bis(6-iodo-2-methyl-4-oxoquinazolin-3(4H)-yl)pyridine-2,6-dicarboxamide. The desired compound was synthesized mechanochemically, using a choline chloride-based deep eutectic solvent as a catalyst. The synthesis took 20 min and the new compound was characterized using different spectral methods. [ABSTRACT FROM AUTHOR]

In this paper, magnetic chitosan is used as a support for the immobilization of copper catalyst (Cu@MChit). The fabricated catalyst is successfully synthesized and characterized by several techniques. The activity of Cu@MChit catalyst is evaluated in the synthesis of novel derivatives of 3-alkyl-2-arylthio-2,3-dihydroquinazolin-4(1H)-ones. The products are synthesized in three simple steps via Chan–Lam coupling reaction. The synthetic route is based on the reaction of isatoic anhydride and an amine, followed by the reaction with carbon disulfide. Cu@MChit-catalyzed reaction of the obtained intermediate with phenylboronic acid leads to the desired products. The scope of the reaction is confirmed by using various amine and phenylboronic acid derivatives and the products are obtained in high isolated yields. [ABSTRACT FROM AUTHOR]

We synthesised a new series of sulphonamide-bearing quinazolinone derivatives 5-18 and evaluated their in vitro cytotoxicity in various cancer cell lines (A549, HepG-2, LoVo and MCF-7) and in normal human cells (HUVEC). Compounds 6 and 10 exhibited the higher activity against all the cancer cell lines compared with 5-flourourcil as positive control. The ability of the most promising compounds 6 and 10 to induce cell cycle arrest and apoptosis in breast cancer (MCF-7) cells was evaluated by flow cytometry. Reverse transcriptase-polymerase chain reaction and western blotting were used to evaluate the expression of apoptosis-related markers. We found that the 2-tolylthioacetamide derivative 6 and the 3-ethyl phenyl thioacetamide derivative 10 exhibited cytotoxic activity comparable to that of 5-fluorouracil as reference drug in MCF-7 and LoVo colon cancer cells. Cell cycle analysis showed a concentration-dependent accumulation of cells in the sub-G1 phase upon treatment with both compounds. The Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that the compounds 6 and 10 increased the early and late apoptosis cell death modes in a dose-dependent manner. These compounds downregulated the expression of B-cell lymphoma-2 (Bcl-2), while increasing that of p53, Bcl-2-like protein 4, and caspase-7, at the mRNA and protein levels. Molecular docking of compounds 6 and 10 with Bcl-2 predicted them to show moderate - high binding affinity (6: -7.5kcal/mol, 10: -7.9kcal/mol) and interactions with key central substrate cavity residues. Overall, compounds 6 and 10 were found to be promising anticancer and apoptosis-inducing agents. [ABSTRACT FROM AUTHOR]

Quinazoline and quinazolinone derivatives display an extensive application in organic and pharmaceutical chemistry, and they have been used as natural and synthetic materials for medicinal chemistry purposes. Here I reported an investigation of a new series of quinazolinone ring derivatives. In this context, starting from the methyl anthranilate, six quinazolinone derivatives (4a-f) with various aminomethyl moieties at position 2 were synthesized (89-80%). The structures of compounds 4a-f were identified using FTIR and NMR Spectroscopy (¹H NMR - 13C NMR). The data obtained from the all spectra clearly identify the structures of the compounds. [ABSTRACT FROM AUTHOR]

A novel series of amino acids conjugated quinazolinone-Schiff's bases were synthesized and characterized by analytical and spectroscopic methods. All the synthesized analogues (8–43) and the intermediates (1–7) were screened for their in vitro antioxidant and anti-inflammatory activities. Antioxidant activities were determined by three different in vitro assays such as DPPH, ABTS and DMPD cation radical activity methods. Compounds 15, 16, 23–25, 30–34 and 39–43 shows potent antioxidants compared to standards gallic acid and ascorbic acid in all the three antioxidants methods. Compounds 9–11, 18–20, 27–29 and 36–38 showed potent anti-inflammatory activity compared to standards indomethacin and ibuprofen. Preliminary structure-activity relationship revealed that the tryptophan and phenylalanine derived compounds with electron donating groups (OH and OCH3) were found to be excellent antioxidant activity compared to glycine and alanine derivatives. Tryptophan and phenylalanine containing compounds with electron withdrawing groups (Cl, NO2 and F) were found to be excellent anti-inflammatory agents.

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial–mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.

In this paper, four new compounds with quinazolinone structure were designed and synthesized based on the special biological activity of quinazolinone. The four new compounds containing quinazolinone structures were synthesized using a one-pot method after intramolecular cyclization and dehydration catalyzed by aqueous methylamine solution. Their structures were characterized using 1H NMR, 13C NMR, FT-IR, and HRMS, and the crystal structure of 2a was characterized using X-ray diffraction. In their potential antifungal activity tests, it was found that the four newly synthesized compounds exhibited significant antifungal activity against all seven phytopathogenic fungi at concentrations of 150 and 300 mg/L. Among them, the target compound 2c showed the best inhibitory effect against Fusarium oxysporum f. sp. Niveum fungus, with 62.42% inhibition at a concentration of 300 mg/L. Compound 2c is expected to be a leading compound for the treatment of watermelon Fusarium wilt in the future, which is worth further study.

As bacteria continue to develop resistance mechanisms against antimicrobials, an alternative method to tackle this global concern must be developed. As the pqs system is the most well-known and responsible for biofilm and pyocyanin production, quinazolinone inhibitors of the pqs system in P. aeruginosa were developed. Molecular docking following a rationalised medicinal chemistry approach was adopted to design these analogues. An analysis of docking data suggested that compound 6b could bind with the key residues in the ligand binding domain of PqsR in a similar fashion to the known antagonist M64. The modification of cyclic groups at the 3-position of the quinazolinone core, the introduction of a halogen at the aromatic core and the modification of the terminal group with aromatic and aliphatic chains were investigated to guide the synthesis of a library of 16 quinazolinone analogues. All quinazolinone analogues were tested in vitro for pqs inhibition, with the most active compounds 6b and 6e being tested for biofilm and growth inhibition in P. aeruginosa (PAO1). Compound 6b displayed the highest pqs inhibitory activity (73.4%, 72.1% and 53.7% at 100, 50 and 25 µM, respectively) with no bacterial growth inhibition. However, compounds 6b and 6e only inhibited biofilm formation by 10% and 5%, respectively.

A green synthetic procedure was developed for the two-step synthesis of methyl 2-((3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)thio)acetate from anthranilic acid, using two green chemistry approaches: utilization of the DES and microwave-induced synthesis. The first step includes a synthesis of 2-mercapto-3-(3-methoxyphenyl)quinazolin-4(3H)-one which was performed in choline chloride:urea DES. In the second step S-alkylation of 2-mercapto-3-(3-methoxyphenyl)quinazolin-4(3H)-one was performed in a microwave-induced reaction. The desired compound was successfully obtained in a yield of 59% and was characterized by different spectral methods. [ABSTRACT FROM AUTHOR]