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A facile synthetic strategy is reported to afford bioactive quinazolinones and aromatic amines by employing amorphous cobalt hollow nanospheres (Co HNS) derived from a Bio‐MOF, cobalt adeninate, as a catalyst. Modulated electron states of the amorphous cobalt with a high concentration of surficial active sites and Co–N sites enhance the intrinsic catalytic activity while the support, activated carbon, facilitates the formation of hollow structure. [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]

An efficient and one‐step synthesis of quinazolinones using 2‐aminobenzamide and benzylamine in DMSO under external catalyst‐ and base‐free conditions is reported. A broad substrate scope and environment‐benign mild reaction conditions are the major attributes of this straightforward synthesis. Moreover, the synthesized quinazolinone derivatives were used to produce pharmaceutically active rutaecarpine analogues using a two‐step reaction: N‐alkylation followed by intramolecular cyclization. [ABSTRACT FROM AUTHOR]

Quinazolinone‐coumarin conjugates synthesized through Late‐Stage Functionalization approach are evaluated for their in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound 23 demonstrating particularly notable cytotoxicity. Further investigation involved a five‐dose assay of compound 23 against NCI‐60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of 23 with HSA, evidenced by a high binding constant (2.26 × 105 M−1). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 104 M−1. This suggests that compound 23 has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Quinazolinone and thiouracil derivatives are key scaffolds in anticancer development. This study used a molecular hybridization approach to synthesize new quinazolinone‐thiouracil derivatives and evaluated their anticancer activity against three human cancer cell lines, namely breast, lung, and glioblastoma, using SRB assay. Structural elucidation was performed using IR spectroscopy, 1H‐NMR, 13C‐NMR, mass spectrometry, and elemental analysis. Most compounds show moderate to significant cytotoxic effects, with compound 5d displaying the highest potency (IC50 values of 5.28, 4.02, and 2.88 µM, respectively). Compound 5d also demonstrated comparable potency to positive controls cisplatin and temozolomide in lung and glioblastoma cancer cell lines and was nearly as effective as mitochondrial division inhibitor‐1 (mdivi‐1). Furthermore, molecular docking analyses revealed strong binding interactions of the synthesized compounds with dynamin‐related protein‐1 (drp1). Protein–ligand stability studies and all‐atom simulation confirmed the stable binding of compound 5d with drp1. In conclusion, this study identified compound 5d as a potent drp1 inhibitor and promising anticancer drug candidate, deserving further investigation. [ABSTRACT FROM AUTHOR]

A convenient and concise base-promoted synthesis of 3,4-dihydro-2(1H)-quinazolinones and multi-membered cyclic ureas has been developed. In the presence of tBuOK, a variety of 3,4-dihydro-2(1H)-quinazolinones as well as the N-arylated five-, six- and nine-membered cyclic ureas were readily synthesized under mild conditions. This method offers an alternative synthesis toolkit towards cyclic ureas. [ABSTRACT FROM AUTHOR]

Objective: Novel 2,3-disubstituted 4-oxoquinazoline-3(4H) derivatives containing oxadiazole, thiazolidinone ring, the 4-oxoquinazoline-3(4H) Schiff bases, and carbothioamide structure were synthesized. All the synthesized compounds' urease and acetylcholinesterase enzyme inhibitions were evaluated in vitro. Methods: The chemical structures of the synthesized compounds were confirmed using IR, 1H, and 13C NMR spectral methods. For all newly synthesized compounds, the urease enzyme inhibition activity was measured using the Weatherburn method, and the acetylcholinesterase enzyme inhibition activity was measured using the Ellman method with slight modifications. Results and Discussion: All newly synthesized compounds showed urease enzyme inhibition in the range of IC50 = 11.00 ± 0.10 to 17.45 ± 0.25 µg/mL compared to standard thiourea (IC50 = 15.75 ± 0.25 µg/mL). Among the synthesized compounds, quinazolinone containing oxadiazole ring (IVa–IVd) and thiosemicarbazide structure (IXa–IXd) showed the most inhibition. Most of the synthesized compounds exhibited good inhibitory activities against acetylcholinesterase compared to the standard inhibitor Galantamine (IC50 = 20.45 ± 0.25 µg/mL), in the range of 16.44 ± 0.26 to 30.50 ± 0.50 µg/mL. Furthermore, the molecular docking study was performed to determine the interaction modes of newly synthesized compounds at the active site of the target enzymes. ADMET properties were calculated to evaluate the drug-likeness of all compounds. Conclusions: In this study, a new series of quinazolinone derivative compounds with potentially active antiurease and antiacetylcholinesterase inhibitions were synthesized, consistent with in silico studies. [ABSTRACT FROM AUTHOR]

A series of novel quinazolinone derivatives (E1−E31) containing the 1,2,4-triazole Schiff base moiety and an isopropanol linker were designed, synthesized and assessed as antimicrobial agents in agriculture. All the target compounds were fully characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry (HRMS). Among them, the structure of compound E12 was further confirmed via single crystal X-ray diffraction method. The experimental results indicated that many compounds displayed good in vitro antibacterial efficacies against the tested phytopathogenic bacteria including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Ralstonia solanacearum (Rs). For example, compounds E3, E4, E10, E13, and E22 had EC50 (half-maximal effective concentration) values of 55.4, 39.5, 49.5, 53.5, and 57.4 µg/mL against Xoo, respectively, superior to the commercialized bactericide Bismerthiazol (94.5 µg/mL). In addition, the antibacterial efficacies of compounds E10 and E13 against Xac were about two times more effective than control Bismerthiazol, in terms of their EC50 values. Last, the antifungal assays showed that compounds E22 and E30 had the inhibition rates of 52.7% and 54.6% at 50 µg/mL against Gibberella zeae, respectively, higher than the commercialized fungicide Hymexazol (48.4%). [ABSTRACT FROM AUTHOR]

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.

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]

New triheteroyclic compounds containing quinazolinone, thiophene, andthiadiazole /thiazolidinone structureswere synthesized and characterized by FT-IR, 1H–NMR, and13C–NMRspectral data. The new compounds' inhibitory activities on urease and acetylcholinesterase were assessed. All triheterocyclic compounds with thiadiazole ring have urease and acetylcholinesteraseinhibitory activities.Especially compound 5a; 3-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl]methyl-2-(thiophen-3-ylmethyl)quinazolin-4(3H)-onehas the best urease inhibition result with 13.30 ± 0.15 µg/mL IC50 value, and it also has the best acetylcholinesterase inhibition with 20.30 ± 0.15 µg/mL IC50 value. [ABSTRACT FROM AUTHOR]

Heterostructures of CuFe2O4@NH2-MIL-88B (Fe) were effectively synthesized and utilized as an effective catalyst under visible light and oxidation conditions for the synthesis of quinazolinones. At room temperature, good to excellent yields of the desired products were obtained. In addition, the composite heterostructures that were created showed a higher level of photocatalytic activity when exposed to visible light compared to both CuFe2O4 and NH2-MIL-88B (Fe) individually. In comparison with CuFe2O4 and MIL-88B (Fe), the absorption peak of CuFe2O4/MIL has increased. Increasing visible light absorption could lead to an increase in electron–hole pair formation, which would improve photocatalytic activity. Furthermore, the incorporation of CuFe2O4 to the NH2-MIL 88B (Fe) surface results in a significant reduction in photoluminescence emission intensity. Moreover, from the perspective of sustainable chemistry, CuFe2O4@NH2-MIL-88B (Fe) demonstrated good recyclability, being recycled six times with little to no loss in catalytic efficacy. [ABSTRACT FROM AUTHOR]

Novel 1,2,3‐triazole acetamide linked quinazolinone derivatives were synthesized via click reaction, by reacting of 3‐methyl‐2‐(prop‐2‐yn‐1‐ylthio)quinazolin‐4(3H)‐one with various aryl azides as prominent fungal pathogen Candida albicans interactions. The prepared triazole compounds were characterized using mass spectrometry, 1H NMR, 13C NMR, and IR spectroscopic techniques. Compounds were screened for their in vitro antibacterial and antifungal activity against a variety of microorganisms namely, Bacillus subtilis, Enterococcus faecalis, Klebsiella pneumonia, Escherichia coli, Aspergillus fumigatus, Candida albicans, and Aspergillus clavatus. Quinazolinone linked p‐hydroxyphenyl, o, p‐dihydroxyphenyl and o‐dimethylamino phenyl triazoles showed a remarkable antibacterial activity against E. faecalis with MIC values of 3.20±0.01, 4.01±0.04, and 4.10±0.01 μg mL−1, and screened compounds p‐nitrophenyl substituted triazole, and p‐methylphenyl substituted triazole displayed a significant antifungal activity against C. albicans with MICs of 3.16±0.01, 4.06±0.03 μg mL−1, compared to itraconazole (MIC=3.32±0.02 μg mL−1). For further exploration of the anti‐fungal mechanism of action, molecular docking was carried out for these compounds in C. albicans active site as one of the important antifungal inhibitors (PDB: 1A19). Furthermore, the ADMET profile was evaluated for all the final triazole compounds in contrast to reference drugs moxifloxacin and itraconazole. In conclusion, we discovered a novel quinazolinone linked 1,2,3‐triazoles with promising antimicrobial activity and a favorable pharmacokinetic profile. [ABSTRACT FROM AUTHOR]

Objective: This research aims to synthesize and characterize a new series of bioactive quinazoline derivatives, including Schiff bases, biquinazolinone, and benzothiazine, and to evaluate their bioactivity as antioxidants through both in silico and in vitro investigations. Methods: The new derivatives were synthesized with high yields by reacting Schiff base derivatives of quinazoline with 2-aminobenzoic acid and 2-mercaptobenzoic acid. The characterization of the prepared derivatives was carried out using FTIR, 1H NMR, and 13C NMR techniques. In silico investigations included assessing pharmacokinetic and pharmacodynamic properties through the SwissADME online server and conducting molecular docking studies with the tyrosinase enzyme. In vitro assessments involved evaluating antioxidant activity using the total antioxidant capacity method and the DPPH scavenging activity method. Results and Discussion: In silico analysis revealed favorable pharmacokinetic and pharmacodynamic properties for all compounds. Compounds (III) and (IV) exhibited acceptable pharmacological characteristics. Molecular docking studies showed good docking scores for all compounds with the tyrosinase enzyme. In vitro assessments demonstrated noteworthy to excellent antioxidant activity for all compounds, with compounds (III) and (IV) exhibiting very strong activity compared to the standard reference, ascorbic acid. Conclusions: The synthesized quinazoline derivatives exhibit promising bioactivity as antioxidants, supported by both computational and experimental assessments. These findings suggest their potential for further exploration in the development of antioxidant agents, with particular emphasis on the notable performance of compounds (III) and (IV). [ABSTRACT FROM AUTHOR]

Copper‐catalyzed and visible‐light catalytic difluoroalkylation reactions of N‐cyanamide alkenes have been developed. Various α‐bromodifluoromethyl substituted esters, amides and heterocycles were employed as the CF2 source. Both protocols are characterized by medium to high yields, good functional group compatibility, and applicable to gram‐scale synthesis. Comparable studies of copper catalysis and photoredox catalysis demonstrate minimal differences between the two protocols. Preliminary mechanism suggest that both transformations involve tandem radical cyclization process. [ABSTRACT FROM AUTHOR]

A novel fluorescent probe (BPQ-1) with large conjugated system (phenothiazine was conjugated with quinazolinone) was synthesized. BPQ-1 showed a remarkable ratiometric fluorescence response to ClO− within 10 s, and achieved large stokes shift (168 nm), high sensitivity (LOD = 16.7 nM) and excellent selectivity. Among the analytes to be detected, there is a significant change from bright yellow fluorescence to cyan fluorescence only when ClO− is added to BPQ-1. Through density functional theory calculation and mass spectrometry experiments, the fluorescence response mechanisms of the BPQ-1 are given. In addition, BPQ-1 has been successfully applied to the detection of ClO− in real water samples and test strips for detecting ClO− with different concentrations have been prepared. In particular, the probe has been successfully applied to the fluorescence imaging of exogenous ClO− in living cells. [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.

Heterocyclic compound such as quinazoline derivatives shows wide range of medicinal application in the area such as anticonvulsant, antitumor, antifungal, antimalaria, anti-hyperlipidemic and anti-inflammatory etc. activity because of these it shows great interest to study. In the presence study, we have synthesized triazole based quinazolinones by condensation reaction between α-methyl ketone and aromatic aldehydes under ethanol as the solvent to produced chalcones derivatives. This chalcone derivative have α,β-unsaturated part which is enhanced the reactivity of compound. Chalcone further reacted with 2-aminotriazole under alkali media in the presence of ethanol as the solvent to produced quinazolinone. This prepared compound has further possibility to modified at N atom upon reaction with halogen containing compound. Prepared quinazolinone were further treated with cyanuric chloride to increase heterocyclic part in the compound. Characterization of all synthesized product were done using spectroscopic techniques. All prepared compounds were screen for their biological evaluation against gram+ve and gram-ve bacteria. [ABSTRACT FROM AUTHOR]

We described a base‐promoted O‐arylation of N3‐hydroxyl quinazolinones with diaryliodonium salts and sequential BF3 ⋅ OEt2 and visible light‐controlled [3,3]‐ or [1,3]‐rearrangements of quinazolinone N−O aryl moieties to prepare a variety of 2‐(quinazolin‐4‐yloxy)phenols and atropisomeric 3‐(2‐hydroxyphenyl)quinazolin‐4‐ones in 44%‐75% yields and 28%‐70% yields, respectively. Mechanistic studies showed that HBF4 generated in situ from BF3 ⋅ Et2O and water served as the catalyst in this process and aryloxyquinazolinium salts are vital intermediates promoting the [3,3]‐ or [1,3]‐rearrangements. The N−O aryl moieties of aryloxyquinazolinium salts were found to undergo solely [3,3]‐rearrangement with heating whereas [1,3]‐rearrangement occurred via a radical process under irradiation of visible light. This method highlights the formation of aryloxyquinazolinium salts based on the use of BF3 ⋅ OEt2 and visible light to prompt [1,3]‐rearrangement generating atropisomeric quinazolinones. [ABSTRACT FROM AUTHOR]

Herein, we reported a selective, mild method for the visible‐light‐photocatalyzed trifluoromethylation and cyclization of unactivated tethered alkenes to provide tri‐ and tetracyclic quinazolinones. Trifluoroacetic acid and anhydride are inexpensive and readily available reagents for the process that proceeds without the addition of a strong oxidant. The wide substrate scope and the formation of 5‐ and 6‐membered rings are demonstrated in 44–82 % yields. Control experiments provide the basis for a proposed mechanism involving photocatalyzed SET from fac‐Ir(ppy)3 to TFAA and trifluoromethyl radical‐mediated regioselective cyclization. The practicality of the protocol was illustrated by a gram‐scale synthesis in 76 % yield. [ABSTRACT FROM AUTHOR]

Some novel 3-aminoquinazolin-4(3H)-one derivatives were synthesized by the reaction of 2-aminobenzhydrazide and corresponding iminoester hydrochlorides and then reacted with coumarin-3-carbonyl chloride to obtain novel coumarin–quinazolinone hybrids. The synthesized hybrid compounds were screened for their anticancer activity against various human cancer and normal cell lines. N-{2-[(4-Bromo- and N-{2-[(3-bromo-phenyl)methyl]-4-oxoquinazolin-3(4H)-yl}-2-oxo-2H-1-benzopyran-3-carboxamides exhibited the highest cytotoxic effect on the PC-3 prostate cancer cell line: IC50 35.3 ± 0.6 and 36.8 ± 0.8 µg/L, respectively. N-{2-[(4-Fluoro-, N-{2-[(4-bromo-, and N-{2-[(3,4-dichloro-phenyl)methyl]-4-oxoquinazolin-3(4H)-yl}-2-oxo-2H-1-benzopyran-3-carboxamides showed the highest activity against the MCF-7 breast cancer cell line: IC50 48.5 ± 0.4, 44.8 ± 0.4 and 46.1 ± 0.5 µg/L, respectively. [ABSTRACT FROM AUTHOR]

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]

The current study outlines a straightforward and efficient method for creating new quinazolinone disperse dyes based on pyrazolone moieties, starting with quinazolinone and a variety of substituted pyrazolone as couplers. The synthesized dyes were characterized using a variety of spectroscopic and analytical methods. The synthesized dyes' ultraviolet–visible spectra showed bands brought on by several molecular transitions. We investigated in detail the multifunctional characteristics such color representation, dyeing duration, concentration, pH, buildup, and fastness properties of the dyed samples. Fastness properties and colorimetric data showed satisfactory results, demonstrating the effectiveness of these dyes in dyeing polyester fabrics. A pH of 5 and a dyeing temperature of 130 °C were the ideal conditions for dyeing polyester fabrics. Additionally, an ultraviolet protection factor test was performed on the dyed fabrics, and the results showed that these dyes provide the best UV protection. These dyes are suitable for industrial dyeing applications since they are easy to manufacture and scale up. Additionally, in-vitro testing was done to determine the dyes' antibacterial effectiveness against various bacteria and fungi. The antibacterial activity of the dyes was moderate to very good against both Gram-positive and Gram-negative bacteria, as well as fungi. [ABSTRACT FROM AUTHOR]

IntroductionThe 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.MethodsThe 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 DiscussionThe 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 BRAFV600E inhibitors. These in vitro tests revealed that compounds 9b, 9c, and 9h are strong antiproliferative agents that may act as dual EGFR/BRAFV600E inhibitors. 9b, 9c, and 9h were further investigated for their inhibitory effect on mutant EGFR (EGFRT790M), 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.

A facile intramolecular [1,5] hydride transfer reaction in a Dihydroquinazolin‐4(1H)‐one moiety synthesized from anthranilamide, glutaraldehyde, and aromatic amines is described in isopropanol medium in the presence of catalytic HCl. Based on that, we have designed a simple, efficient strategy for conjugating quinazolinone, a pharmaceutically active moiety, with an aromatic amine through an aliphatic spacer. The use of isopropanol as a reaction medium at RT and isolation of the product without rigorous column purification make the process a step ahead towards sustainability. One of the synthesized compounds was evaluated as a small molecule DNA binder. Detailed binding properties were investigated by the multispectroscopy methods. [ABSTRACT FROM AUTHOR]

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]

This paper presents a amidinyl transfer reagent for the synthesis of nitrogen‐containing compounds, wherein N,N‐dimethylformamide is used as the C1 source to react with hexamethyldisilazane, generating the N,N‐dimethylformimidamide intermediate. This intermediate is then reacted with amines to induce amidinyl transfer. This protocol can be applied for the synthesis of N‐formamide, benzimidazole and quinazolinone, for which amine derivatives used as substrates under optimized conditions. The advantages of this method are its operational simplicity, high efficiency, structural diversity in products with favorable yields, and applicability in gram‐scale operations. [ABSTRACT FROM AUTHOR]

An efficient palladium‐catalyzed annulation of 3‐arylquinazolinones with mono and double alkyne insertion was developed for the synthesis of fused quinazolinone derivatives in 43–80 % yields. A notable effect was observed in product yield, when bases/additives were modulated. The reaction mechanism is believed to proceed through C−X cleavage/alkyne insertion/1,4‐Pd migration and C−H annulation in a one‐pot manner. [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]

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]

In the current study, a series of 1,3,4-oxadiazole and 1,2,4-triazole derivatives linked to quinazolinone were designed and synthesized by using Phase Transfer Catalysis. The structures of the synthesized compounds were confirmed by their IR, 1H NMR, 13C NMR, and HR-ESI-MS spectroscopic data, and their in vitro antiproliferative activities against A549, Hela, MCF-7 as well as L929 were detected by using CCK-8 assay. The results demonstrated that most of the compounds showed better growth inhibitory effect than 5-FU on A549, Hela, and MCF-7 cell lines. Especially, 2-(5-((3-bromophenyl)thio)-1,3,4-oxadiazole-2-yl)quinazolin-4(3H)-one (8o), 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) and 2-(4-amino-5-(o-tolylthio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9b) showed good antiproliferative activity against A549 cells with IC50 value of 3.46, 2.96, and 3.44 μM, respectively. 2-(4-Amino-5-((3,5-difluorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9h) and 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) had obvious inhibitory effects on Hela cells with IC50 values of 1.76 and 3.91 μM, respectively. 2-(4-Amino-5-((2-chlorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9i) showed high inhibitory activity against MCF-7 cells with IC50 value of 2.72 μM. Meanwhile, all compounds showed lower cytotoxicity to L929 cells than positive control drug 5-FU. In development, according to the above preliminary observation, these novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties could become potential molecular templates for searching new antitumor agents. [ABSTRACT FROM AUTHOR]

Facile synthesis for true intermediate (E)‐ and Z‐2‐(((5‐bromo‐1‐(3‐chloropyridin‐2‐yl)‐1H‐pyrazol‐3‐yl)methylene)amino)‐5‐chloro‐3‐methylbenzoic acid precursors and 2‐(5‐bromo‐1‐(3‐chloropyridin‐2‐yl)‐1H‐pyrazol‐3‐yl)‐6‐chloro‐3,8‐dimethylquinazolin‐4(3H)‐one (QPP) as electron donor/electron acceptor to be working as efficient dye sensitizers. These new derivatives have a wide‐band gap photo‐catalysts semiconductor and are performing to spread to the visible‐light region to give more stability and efficiency towards biomedicine for different diseases. In the present work, the authors are suggesting the design and synthesis of new structures of QPP molecule with extended visible light absorptivity due to the extended π‐π/n‐π conjugations, to stimulate TiO2 nanoparticles in visible‐light region. The physicochemical characterizations confirmed the successful synthesis of QPP, TiO2, and QPP II/TiO2 samples with the proposed structures. Fixing of QPP on the TiO2 surface is refining the optical properties of TiO2 with enhancing the charge separation and generating the efficient antenna in the visible region. Furthermore, the QPP II/TiO2 sample achieved a threefold enhancement in the observed rate constant of the photo‐degradation of rhodamine B dye when compared to the bare TiO2. Finally, the effect of the scavengers was investigated by O2.− to be the most reactive species, and the mechanism of the enhancement was suggested for investigation of the proposed structures in various photo‐catalytic and biomedical applications. [ABSTRACT FROM AUTHOR]

Fluorescent organic nanoparticles (FONPs) have attracted much attention as a practicable and effective platform for detection applications. The present article describes the preparation of FONPs derived from the quinazolinone-based 2-(furan-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivative FHDQ. Self-assembly of FHDQ in an aqueous medium resulted in the formation of FONPs through H-type aggregation and showed excellent fluorescence properties. The presence of other coexisting species solutions did not affect the selective fluorescence quenching observed with the addition of 4-nitrophenol (4-NP). The photophysical properties, i.e., UV-Vis absorbance, fluorescence emission, and lifetime measurements together with zeta particle sizer, support excited-state complex formation followed by a dynamic fluorescence quenching phenomenon in the emission of FDHQNPs. In the concentration range of 0 to 36 μg. mL - 1 , the detection limit of this turn-off sensor FDHQNPs against 4-NP was determined to be 0.01611 μM. Finally, the practicability of the FDHQNPs for the analysis of 4-NP in environmental samples was demonstrated. [ABSTRACT FROM AUTHOR]

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-(1H)-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-(1H)-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 IC50 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.

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.

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.

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.

A three‐step synthesis of anti‐amoebic, ring‐fused mackinazolinones has been developed. A Mannich‐type reaction between quinazolin‐4‐ones and N‐Cbz propanal in the presence of AgOTf afforded quinazolinones (19–94% isolated yield) bearing a newly formed heterocycle with an alkylamine appendage that, upon N‐Cbz deprotection and basification, triggered a domino rearrangement to afford 45 separable, ring‐fused products. Several compounds inhibited growth of Naegleria fowleri parasites that can cause a lethal human brain infection. Thus, the methodology provides immediate access to a promising anti‐amoebic scaffold. [ABSTRACT FROM AUTHOR]

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]

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]

In this study, we focused on the ultrasonic synthesis of titanium dioxide (TiO2) nanoparticles via a green chemistry process using Citrus limon (lemon) juice. XRD diffractograms and Raman spectroscopy revealed the anatase structure of TiO2, SEM analysis showed nanometric particle sizes, and FTIR spectroscopy confirmed the presence of the synthesized nanoparticles. The catalytic performance of the biosynthesised nanoparticles was evaluated for the synthesis of sulphur-substituted quinazolinone derivatives under UV irradiation. The final products were achieved in 6–8 h with good yields (79–91%). [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]

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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.

A short and expeditious total and diverted total synthesis of luotonin, vasicinone, and their analogues has been achieved from the key tricyclic quinazolinone intermediate which was accessed from simple substituted anthranilamide obtained from the coupling of β‐alanate with isatoic anhydride followed by Dieckmann condensation chemistry of the resulting diester. The tricyclic ketone exhibited interesting chemical properties, e. g. keto‐enol tautomerism. Friedlander condensation and Fischer‐Indolization were employed for further annulations to access polycyclic alkaloids and their analogues. [ABSTRACT FROM AUTHOR]