Search

Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a notorious recreational drug in the 1960s-80s. Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance. Methaqualone principally targets GABAA receptors, which are the major inhibitory neurotransmitter-gated ion channels in the brain. The restricted status and limited accessibility of methaqualone have contributed to its pharmacology being understudied. Here, we use cryo-EM to localize the GABAA receptor binding sites of methaqualone and its more potent derivative, PPTQ, to the same intersubunit transmembrane sites targeted by the general anesthetics propofol and etomidate. Both methaqualone and PPTQ insert more deeply into subunit interfaces than the previously-characterized modulators. Binding of quinazolinones to this site results in widening of the extracellular half of the ion-conducting pore, following a trend among positive allosteric modulators in destabilizing the hydrophobic activation gate in the pore as a mechanism for receptor potentiation. These insights shed light on the underexplored pharmacology of quinazolinones and further elucidate the molecular mechanisms of allosteric GABAA receptor modulation through transmembrane binding sites.

BACKGROUND: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. RESULTS: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. CONCLUSIONS: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

Visible light‐driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging‐to‐access axially chiral 2‐azaarene‐functionalized quinazolinones. The substrate scope is extensive, allowing for both 3‐axis and unmet 1‐axis assembly through facile oxidation of diverse central chiral 2,3‐dihydroquinazolin‐4(1H)‐ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization. [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]

Two different one‐pot synthetic protocols have been developed for obtaining 2,3‐disubstituted quinazolin‐4(3H)‐ones using pyridinium p‐toluenesulfonate (PPTS) as catalyst. The two‐component reaction involves isatoic anhydride and N‐acetyl amine whereas the three‐component reaction use isatoic anhydride, aryl amine and β‐diketone in Toluene under classical heating at 80–100 °C to afford 2,3‐disubstituted quinazolin‐4(3H)‐ones in good yields. The two‐component reactions are compatible with various substituted aryl/alkyl amines. [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]

In this study, a new deep eutectic mixture (DEM) was prepared from D-fructose, L-arginine, and urea and characterized by Fourier transform infrared (FT-IR), refractive index measurement, and thermogravimetric analysis (TGA). In continue this mixture was used as a green catalyst to promote the synthesis of three important derivatives of heterocyclic compounds. The highlights of this work include some notable advantages such as ease of the preparation and simple catalytic process, low cost, green reaction conditions, biodegradability of the catalyst, short reaction times, high yields of the products and simple work-up. Also, the catalyst could be recovered easily and reused up to several times without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

The reaction of 2-(trifluoromethyl)-3,1-benzoxazone with amines was studied. At first, when one mole equivalent of 2-(trifluoromethyl)-3,1-benzoxazone was treated with one mole equivalent of phenylenediamine afforded bis-benzamide derivatives rather than 3-(aminophenyl)quinazolinone derivatives. Many trials to obtain the 3-(aminophenyl)quinazolinones were carried out, and the final result is that it is difficult to obtain the 3-(aminophenyl)quinazolinones in acceptable yield and purity from the reaction of phenylenediamine with 2-(trifluoromethyl)-benzoxazinone. The synthesis of new 6-iodo-3-substituted-2-(trifluoromethyl)quinazolin-4(3H)-one derivatives was studied as follows: when the 6-iodo-2-(trifluoromethyl)-3,1-benzoxazin-4-one was fused with some amines at 140 °C for 10 min, it afforded 5-iodo-N-(methyl and aryl)-2-(trifluoroacetamido)benzamide derivatives. While, when 6-iodo-2-(trifluoromethyl)-3,1-benzoxazinone was condensed with the same amines in acetic acid under reflux conditions, it afforded 6-iodo-3-(methyl and aryl)-2-(trifluoromethyl)quinazolin-4(3H)-one derivatives. Condensation of the 6-iodo-2-(trifluoromethyl)-3,1-benzoxazinone with hydrazine hydrate gave 3-amino-6-iodo-2-(trifluoromethyl)quinazolinone. Condensation of the latter 3-aminoquinazolinone with some aldehydes and isatin afforded the corresponding Schiff's bases. The expected antimicrobial properties of the synthesized compounds were investigated. Most of the compounds showed moderate effects on some bacteria. Most compounds had no effects on fungi. Schiff's base of isatin showed the best results among all the tested compounds. The latter Schiff's base showed potent activity, like ketoconazole toward fungi. [ABSTRACT FROM AUTHOR]

Herein we first report the unprecedented synthesis of tetrazene‐based cobalt complexes using unusual coupling of amines via dehydrogenation. These cobalt complexes were employed for dehydrogenative coupling reactions to synthesize N‐heterocycles (quinoline, and quinazolinone). Based on control experiments and IR identification of intermediates, we proposed a plausible reaction mechanism. Synthesis protocols were utilized for preparative scale synthesis and biologically active molecule (±)‐galipinine synthesis. [ABSTRACT FROM AUTHOR]

The synthesis of acylmethylatated pyrrolo‐quinazolinones was developed via photo‐induced cascade radical addition/cyclization of N‐(but‐3‐enyl)quinazolin‐4(3H)‐ones with sulfoxonium ylides using 4CzIPN as the photocatalyst. This approach was also suitable for the construction of acylmethylatated piperidino‐quinazolinones. This protocol features with mild conditions, convenient operation, broad substrate scope and good functional group compatibility. [ABSTRACT FROM AUTHOR]

Nitrogen‐containing heterocycles represent fundamental components found in a myriad of natural compounds, pharmaceuticals, tailored bioactive substances, and agrochemicals. In recent decades, the field of synthetic chemistry has prioritized these compounds, directing considerable research endeavour toward developing efficient and concise methodologies for their synthesis. Consequently, there is a growing interest in pioneering novel synthetic approaches to fabricate these immensely coveted structural motifs. Transition metal‐catalyzed reactions leveraging solvents as carbon (C1) synthons offer notable advantages, including streamlined processes, enhanced atom economy, and environmental sustainability. This review sheds light on the recent advancements in the utilization of collective solvents such as methanol (alongside other alcohols), N,N‐dimethylethanolamine (DMEA), and triethylamine (TEA) (in conjunction with other amines), tetrahydrofuran (THF), toluene, dichloromethane (DCM), dimethyl sulfoxide (DMSO), and dimethylformamide (DMF) as C1 synthons, serving as foundational units for the synthesis of N‐heterocycles, including quinazolinone, quinazoline, quinoxaline, pyridine, and pyrimidine, among others. Various reaction conditions employing diverse transition metals, coupling partners, and solvents as carbon synthons or reagents, as reported in the literature, have been explored. [ABSTRACT FROM AUTHOR]

Primary alcohols 2(a–h) and o‐aminobenzamides 1(a–h) can be selectively oxidized electrochemically to yield dihydroquinazolinone 4(a–h) and quinazolinones 5(a–h) in an efficient and chemoselective manner. This methodology employs sodium chloride (NaCl) 3(a) as a co‐catalyst and electricity as the oxidizing agent, utilizing cost‐effective and commercially available materials such as Graphite anode, Iron (Fe) cathode, and isopropyl alcohol (iPrOH) as a solvent and weak base. The synthesis yields various quinazolinone derivatives with diverse structural characteristics in good quantities, showcasing the method's broad applicability. This approach facilitates the production of a range of dihydroquinazolinones and quinazolinones (24 examples), highlighting its versatility and compatibility with different functional groups. Characterization of the synthesized derivatives included CHN analysis, 1HNMR spectroscopy, and determination of melting points. [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]

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]

We described a copper(I)‐catalyzed atom economic and selective hydroamination‐cyclization of alkynyl‐tethered quinazolinones to prepare a variety of indole‐fused pyrazino[1,2‐a]quinazolinones in good to excellent yields ranging from 39 %–99 % under mild reaction conditions. Control experiments revealed that coordination‐directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination‐cyclization of alkynes at the N1‐atom instead of N3‐atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole‐fused pyrazino[1,2‐a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions. [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]

Quinazolinone derivatives have garnered attention for their diverse biological activities, including anticancer properties. This review combines findings from 2018 to 2024, focusing on the impact of quinazolinones on cancer cells, tubulin formation, and EGFR/PI3 K pathways. By unraveling the intricacies of structure‐activity relationships, this review endeavors to provide guidance for researchers in identifying promising avenues for the development of cancer treatments. Although in vitro studies underscore significant potential, it is imperative that future research prioritizes pre‐clinical investigations to seamlessly traverse the transitional phase towards clinical applications, thereby propelling the advancement of quinazolinone‐based cancer therapy. [ABSTRACT FROM AUTHOR]

A gentisic acid based-Deep Eutectic Solvent (MTPPBr/GA-DES) was synthesized by mixing one mole of methyl triphenylphosphonium bromide (MTPPBr) and one mole of gentisic acid (GA: 2,5-dihydroxy-benzoic acid) based on the eutectic point phase diagram. Then, it was characterized by FT-IR, NMR, densitometer, and TGA/DTA techniques and used as a potent and novel catalyst for the fast and green synthesis of: (i) Five new 2(a-e) and five known 2(f-j) benzo[6,7]chromeno[2,3-d]pyrimidines and (ii) One new (3a) and eleven known 3(b-l) pyrano[2,3-d]pyrimidines, in solvent-free conditions, short reaction times, and high yields. It is important to mention that for the synthesis of 2(a-j), there is only one reference which states that the reaction times are extremely long (720–2400 min), while these times are reduced to approximately 35–50 min in our proposed strategy, indicatinging that the rate of reactions will be 20–48 times faster, which is the clear and most obvious advantage of our approach. [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]

A novel visible-light promoted metal-free radical cascade cyclization reaction has been developed with 3-allyl-2-arylquinazolinones as a new class of radical acceptor. This photocatalytic protocol represents an efficient approach to construct phosphorylated dihydroisoquinolino[1,2-b]quinazolinones featuring mild conditions, broad substrate scope, and gram-scale synthesis. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A new, selective Ru(II)‐catalyzed alkynylation reaction of isoquinolones, quinazolones and phthalazinones with readily available bromoalkynes has been developed. This reaction enables the selective construction of a new C(sp2)‐C(sp) bond through C—H activation and C—Br functionalization, and offers an effective and selective route to synthesizing highly valuable alkynylated isoquinolone, quinazolone and phthalazinone derivatives with a wide substrate scope and high selectivity. [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]

A highly efficient cascade annulation approach is developed for the synthesis of novel quinazolinone-based spirocyclopropanes via three-component [3 + 2] cycloaddition reaction with aldehydes, tosylhydrazide and quinazolinyl chalcones. The reaction features the formation of two C–C bonds and three stereogenic centers. A variety of highly functionalized spirocyclopropyl quinazolinones were obtained in good yields under mild reaction conditions. Furthermore, in silico anti-tubercular (anti-TB) molecular docking studies were performed for the generated compounds against three Mycobacterium tuberculosis proteins with PDBID: 1DF7, 1P44 and 4TZK. ADME prediction were evaluated for the drug like properties of the synthesized compounds. [ABSTRACT FROM AUTHOR]

A visible-light-induced K2S2O8-promoted cascade sulfonation/cyclization reaction was established using 3-(2-(ethynyl)phenyl)quinazolinones as efficient substrates under mild conditions. A series of sulfonated quinolino[2,1-b]quinazolinones were successfully synthesized under transition-metal- and photocatalyst-free conditions. Notably, this strategy has the advantages of room temperature and simple operation, easy scale-up, and good functional group tolerance. [ABSTRACT FROM AUTHOR]

The present work reports the synthesis of multi-wall carbon nanotubes (MWCNTs) over graphite nanosheets by an easy and simple approach without using any external catalyst. Simply, yellow corn seeds were thermally annealed in a hydrogen atmosphere at 1050 °C for 3 h without any pretreatments. Notably, the growth of MWCNTs was observed to preferentially occur on the outer surface of the corn shell. This uncomplicated approach not only emphasizes the feasibility of synthesizing carbon nanomaterials using agricultural by-products but also underscores the potential applications of these synthesized materials in various fields. Samples were examined through a comprehensive analysis employing various techniques, including scanning electron microscopy (SEM), Raman spectroscopy, FTIR, X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HRTEM). The findings unveiled the formation of rolled graphene accompanied by the presence of vertical multi-wall carbon nanotubes (MWCNTs) positioned over stacked graphene sheets. This detailed characterization provides insights into the structural features and arrangement of the synthesized materials, paving the way for a deeper understanding of their potential applications. The pyrolysis temperature is a crucial factor in the morphological characteristics of the synthesized carbon nanostructures. While graphene cage-like structures were obtained at 800 °C, small carbon nanotubes were grafted to larger ones and formed three-dimensional hierarchical morphologies when the annealing temperature increased to 900 °C. The growth mechanism of the carbon nanotubes was explained based on the jet self-extrusion of the generated gases through the inherent pores of the corn seeds. The current technique employed in manufacturing MWCNTs shows significant promise as a green synthesis method for producing catalyst-free MWCNTs suitable for industrial applications including sensors and energy storage materials. [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]

Herein, we report a solely ligand centered redox controlled protocol, utilizing a bench stable zinc compound, for the efficient coupling of o-amino amides/esters with nitriles to afford diverse quinazolinone scaffolds and their synthetic utility was showcased via post-modification to access therapeutically relevant compounds. Importantly, mechanistic probes established the reaction pathway that proceeds via aminyl radical. [ABSTRACT FROM AUTHOR]

The canonical visual cycle employing RPE65 as the retinoid isomerase regenerates 11-cis-retinal to support both rod- and conemediated vision. Mutations of RPE65 are associated with Leber congenital amaurosis that results in rod and cone photoreceptor degeneration and vision loss of affected patients at an early age. Dark-reared Rpe65-/- mouse has been known to form isorhodopsin that employs 9-cis-retinal as the photosensitive chromophore. The mechanism regulating 9-cis-retinal synthesis and the role of the endogenous 9-cis-retinal in cone survival and function remain largely unknown. In this study, we found that ablation of fatty acid transport protein-4 (FATP4), a negative regulator of 11-cis-retinol synthesis catalyzed by RPE65, increased the formation of 9-cis-retinal, but not 11-cis-retinal, in a light-independent mechanism in both sexes of RPE65-null rd12 mice. Both rd12 and rd12; Fatp4-/- mice contained a massive amount of all-trans-retinyl esters in the eyes, exhibiting comparable scotopic vision and rod degeneration. However, expression levels of M- and S-opsins as well as numbers of M- and S-cones surviving in the superior retinas of rd12;Fatp4-/- mice were at least twofold greater than those in age-matched rd12 mice. Moreover, FATP4 deficiency significantly shortened photopic b-wave implicit time, improved M-cone visual function, and substantially deaccelerated the progression of cone degeneration in rd12 mice, whereas FATP4 deficiency in mice with wild-type Rpe65 alleles neither induced 9-cis-retinal formation nor influenced cone survival and function. These results identify FATP4 as a new regulator of synthesis of 9-cis-retinal, which is a "cone-tropic" chromophore supporting cone survival and function in the retinas with defective RPE65. [ABSTRACT FROM AUTHOR]

The indispensable role of α‐arylated compounds in chemistry can be accounted from its presence in various pharmaceuticals we use in our daily life. Chemists are establishing diverse methods for the synthesis of various α‐arylated compounds by considering their applications in different fields including biology, medicine, agrochemicals, material science, etc. Diverse pharmacologically active compounds, natural products, and drugs contain α‐arylated carbonyl groups in their structure. The impact of transition metal catalysis in chemistry is overwhelming, among which palladium is the predominant due to its high reactivity as well as catalytic potential. α‐Arylation reactions with palladium catalysts have been successful in producing a variety of desired chemicals. The formation of active pharmaceutical ingredients and total synthesis of natural products can now be achieved by the development of novel pathways through the α‐arylation of carbonyl compounds, catalyzed by palladium. Wide variety of simple arylating agents could be used under the condition of palladium catalysis. Syntheses that utilize α‐arylation methods often offer advanced ways that improve overall yields, expand the scope of the synthesis, and reduce the steps. One of the synthetic achievements is the increased selectivity obtained with lower amounts of the catalyst. Gentle reaction conditions were employed, and broad substrate scope was accomplished. Recent advances in the α‐arylation reactions of various compounds, catalyzed by palladium, is discussed in this review covering literature from 2016 to 2022. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fluorine plays a significant role in agrochemical science because approximately 25% of herbicides licensed worldwide contain this element. In a pool of previously synthesized benzoxazinones, some compounds contained fluorine and demonstrated inhibitory activities against protoporphyrinogen IX oxidase (PPO). Therefore, three data sets of benzoxazinone derivatives with known inhibitory activity against PPO were employed to build a multivariate image analysis applied to a quantitative structure–activity relationships (MIA‐QSAR) model to identify improved analogs with at least one fluorine substituent. RESULTS: The QSAR model was vigorously validated and demonstrated to be highly predictive (r2 = 0.85, q2 = 0.71, and r2pred = 0.88); thus, the model can provide reliable estimations for the PPO inhibitory activity of unknown derivatives. From these compounds, a couple of N‐substituted benzoxazinones that contained the ‐CH2CHF2 group were found with predicted pKi values larger than 8 (Ki in mol L−1) and higher lipophilicity than the most active data set compounds. In addition, we carried out a systematic investigation of the binding mode of PPO by performing computational docking followed by molecular dynamics simulations. The proposed binding mode was consistent with experimental studies, and several potential key residues were identified. CONCLUSION: Two new proposed benzoxazinones exhibited better performance than compounds of the data set, and fluorine substituents played pivotal roles in describing the biological activities. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A series of 5-Aryl-1,2,4-triazole derivatives linked by Quinazolin-4-one thioether were designed and synthesized through condensation reactions. The structure of the synthesized compounds was characterized using IR, NMR, and mass spectroscopy. The synthesized triazoles, coded as NSS-T, were evaluated for their in silico biological profile through molecular docking and for their in vitro anticancer and antimicrobial activity. In silico molecular modeling studies for the synthesized hybrids have shown good molecular interactions with EGFR and HDAC6 cancer targets and Sterol 14-α demethylase fungal target. From in vitro studies, all compounds were found to be active against MCF-7 (breast), A549 (lung), SiHa (cervix), and Colo 205 (colon) besides inhibitory active against Gram-negative, Gram-positive bacterial strains as well as selected fungal strains (C. albicans). [ABSTRACT FROM AUTHOR]

The given text consists of multiple articles and documents related to the synthesis and characterization of various compounds. These compounds have potential biological activities and are synthesized using different reactions and characterized using spectroscopic techniques. The articles provide detailed information on the synthesis methods, experimental conditions, and characterization data for each compound. The text also includes a graph that visually represents data on a specific topic, which can be helpful for researchers conducting further studies. [Extracted from the article]

A convenient route for the preparation of tetrahydropyran (THP) derivatives with a quaternary and tertiary vicinal stereocenters is reported. The atom economy acid‐catalyzed cyclization of allylsilyl alcohols provided polysubstituted tetrahydropyrans in good yields and excellent diastereoselectivities (>95 : 5). In comparison with the traditional oxymercuration procedure, this approach resulted to be more efficient in both yield and stereocontrol. [ABSTRACT FROM AUTHOR]

A TfOH-mediated, metal-free protocol for the synthesis of spiro-furan/pyran quinazolinones through a cascade hydroalkoxylation and intramolecular amide-cyclization reaction of alkynol ureas has been unveiled. This methodology facilitates the generation of highly functionalized spiro-heterocycles with remarkable yields and exclusive regioselectivity. Furthermore, the applicability of the strategy extends to the synthesis of spiro-pyrrolidine quinazolinones. Finally, post-synthetic modification incorporates bromide functionality into the synthesized spiro-heterocycle. [ABSTRACT FROM AUTHOR]

An additive‐free, mild, and regioselective C(1)−H nitration of imidazo[1,5‐a]pyridine derivatives was developed. This protocol features the use of easily handled, commercially available, and nontoxic Fe(NO3)3 ⋅ 9H2O both as a nitration source and as a promoter, exhibits good functional group compatibility, and generates the desired nitrated products in acceptable to excellent yields. Mechanistic studies proposed that the nitration reaction may involve a radical C−H functionalization process. [ABSTRACT FROM AUTHOR]

Herein, a heterogeneous Pd/C-catalyzed direct one-step four-component double carbonylative approach for cascade synthesis of 2-aryl quinazolinones has been reported for the first time starting from 2-iodoaniline derivatives and aryl iodides. The given reaction involves the simultaneous implementation of two different gaseous surrogates i.e., ammonium carbamate as an NH3 precursor and oxalic acid as a bi-functional reagent acting as a CO as well as a C-atom surrogate under ligand-free conditions. [ABSTRACT FROM AUTHOR]

An iron(II)‐catalyzed cascade reaction, involving cyanoalkylsulfonylation and cyclization, has been devised to enable the synthesis of functionalized sulfonylated quinolino‐quinazolinone alkyl nitriles. This three‐component radical transformation exhibits excellent chemo‐ and regioselectivity while functioning without the need for external oxidizing or reducing agents. The cost‐effectiveness of this catalytic system, together with its broad substrate application, which includes drug molecule derivatives, make this approach efficient and adaptable. [ABSTRACT FROM AUTHOR]

Heteroatoms are very important in polyoxometalates (POMs) because they can lead to appealing architectures and unexpected properties in the final POMs. In this work, we elaborately designed and isolated three Silverton-type POMs ([UIVMo12O42] 8−) with UIV as the heteroatom and linked by FeII (FeUMo), CoII (CoUMo) and NiII (NiUMo). These Silverton-type U-containing polyoxomolybdates were demonstrated to be the first molecular catalysts for the synthesis of quinazolinone drug precursor skeletons. Under the optimized reaction conditions, 27 quinazolinones could be obtained in high yield with water as the sole by-product under mild conditions. Furthermore, NiUMo can be recycled seven times and still keep high stability and catalytic activity. [ABSTRACT FROM AUTHOR]

An effective and environmentally friendly technique for synthesizing hybrid molecules based on schizocommunin has been detailed in this study. This process involves a click reaction utilizing quinazolinones, isatin, and azides. Schizocommunin, a natural bioactive compound recognized for its wide array of biological functions including its anticancer properties, was employed as the foundational scaffold. The resultant triazo compounds originating from schizocommunin were subjected to thorough evaluation for their potential anticancer activity against three human cancer cell lines: MCF-7 (breast cancer), A549 (lung cancer), and PC-3 (prostate cancer), through employment of the MTT assay. One compound from the series showcased a remarkable anticancer efficacy (IC50 2.35 ± 0.67 μM) against MCF-7. [ABSTRACT FROM AUTHOR]

This work reports on an inhibition and adsorption performance study of two quinazoline derivatives ((2-(2-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one) and (2-(2,4- dichlorophenyl)-2,3-dihydroquinazolin-4(1H)-one)) named ZB3 and ZB4, which were synthesized and examined using carbon nuclear magnetic resonance (13C NMR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The assessment of the corrosion prevention of these two compounds for MS in 1.0 M HCl was performed employing potentiodynamic polarization (PDP) and (EIS) electronic impedance spectroscopy. The experiments performed showed that both derivatives operate well to prevent corrosion and their efficiencies exceed 85% at a concentration of 10-3. Moreover, it is discovered that the three chemicals' adsorption on the m-steel surface complies with Langmuir adsorption isotherm equation. The m-steel surface submerged in the corrosive solution was characterized by scanning electron spectroscopy (SEM) in conjunction with energy dispersive spectroscopy (EDS), spectroscopy using atomic force microscopy (AFM), X-Ray diffraction, and FTIR analysis. The findings showed that the examined inhibitors are well adsorbed, generating a barrier layer for the msteel's surface. DFT calculations and Monte Carlo (MC) simulation were used to directly correlate the electronic and adsorption properties, respectively, with the experimental corrosion inhibition efficiencies obtained for quinazoline and its 2 investigated derivatives. [ABSTRACT FROM AUTHOR]

Due to the rapid growth in the number of patients with diabetes in a complicated epidemiological picture, the question of the possibility of exposure of a substance to several targets becomes more important. It is noted that the most common infectious diseases in patients with diabetes mellitus are infections of the respiratory and urinary tract, skin and soft tissues, diabetic foot ulcers, otitis media and periodontal infections. Antimicrobial agents can have both direct and indirect hypoglycemic effects. Quinazolinones belonging to the group of heterocyclic derivatives exhibit a wide range of pharmacological activity. The use of the PASS program for the purpose of computer prediction of pharmacological activity showed a high probability of the hypoglycemic effect of new derivatives. The obtained results motivated the authors to search for the relationship between antimicrobial action and hypoglycemic effect within the general direction of studying the multi-targeting of drug ligands. Analysis of the literature data, as well as own studies of new quinazolinone derivative pharmacological activity make it possible to divide all ligands into functional groups that cause additional binding to the target molecule. The quinazolinone fragment, characterized by the uniqueness of its structure, can be reasonably attributed to multi-target ligands. The triazole cycle and the sulfonamide group can also purposefully bind to the target molecule. A carbamide residue, a fragment of sulfonylurea and an acetamide group, depending on the structure of the substance they are part of, can function both as a specific ligand and as a functional group involved in the stabilization of the intermediate transition state. The results obtained by the authors, as well as other researchers, allow us to formulate an assumption about the relationship between the mechanisms of antimicrobial and hyperglycemic activity.

Unprecedented ring-opening polymerization of quinazolinones to produce novel polyacylamidines, led by a unique cooperation between a cesium metal center and imino-phosphanamidinate ligand, was developed. Morphological studies revealed the formation of a unique macromolecular assembly producing nanofibers in the absence of a templating agent with excellent control of molecular weights and polydispersity index. [ABSTRACT FROM AUTHOR]

Background: The continuous progress in nanotechnology is rapid and extensive with overwhelming futuristic aspects. Through modernizing inventive synthesis protocols, a paradigm leapfrogging in novelties and findings are channeled toward fostering human health and sustaining the surrounding environment. Owing to the overpricing and jeopardy of physicochemical synthesizing approaches, the quest for ecologically adequate schemes is incontestable. By developing environmentally friendly strategies, mycosynthesis of nanocomposites has been alluring. Results: Herein, a novel architecture of binary CuO and TiO2 in nanocomposites form was fabricated using bionanofactory Candida sp., for the first time. For accentuating the structural properties of CuTi nanocomposites (CuTiNCs), various characterization techniques were employed. UV-Vis spectroscopy detected SPR at 350 nm, and XRD ascertained the crystalline nature of a hybrid system. However, absorption peaks at 8, 4.5, and 0.5 keV confirmed the presence of Cu, Ti and oxygen, respectively, in an undefined assemblage of polygonal-spheres of 15–75 nm aggregated in the fungal matrix of biomolecules as revealed by EDX, SEM and TEM. However, FTIR, ζ-potential and TGA reflected long-term stability (− 27.7 mV) of self-functionalized CuTiNCs. Interestingly, a considerable and significant biocide performance was detected at 50 µg/mL of CuTiNCs against some human and plant pathogens, compared to monometallic counterparts. Further, CuTiNCs (200 µg/mL) ceased significantly the development of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans biofilms by 80.3 ± 1.4, 68.7 ± 3.0 and 55.7 ± 3.0%, respectively. Whereas, 64.63 ± 3.5 and 89.82 ± 4.3% antimicrofouling potentiality was recorded for 100 and 200 µg/ml of CuTiNCs, respectively; highlighting their destructive effect against marine microfoulers cells and decaying of their extracellular polymeric skeleton as visualized by SEM. Moreover, CuTiNCs (100 and 200 µg/ml) exerted significantly outstanding disinfection potency within 2 h by reducing the microbial load (i.e., total plate count, mold & yeast, total coliforms and faecal Streptococcus) in domestic and agricultural effluents reached >50%. Conclusion: The synergistic efficiency provided by CuNPs and TiNPs in mycofunctionalized CuTiNCs boosted its recruitment as antiphytopathogenic, antibiofilm, antimicrofouling and disinfectant agent in various realms. [ABSTRACT FROM AUTHOR]

Herein, we report a nickel‐catalyzed intramolecular dual annulation reaction of alkyl nitrile‐containing 1,2,3‐benzotriazin‐4(3H)‐ones to synthesize polycyclic quinazolinones. This catalytic reaction can construct the core structure of polycyclic quinazolinone alkaloids; therefore, we also apply this reaction as the critical step to access fifteen relevant alkaloids to demonstrate efficacy. [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]

Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1− = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2− = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3− = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug. [ABSTRACT FROM AUTHOR]

An efficient electrochemical dual C(sp3)–H amination was developed under metal-free and chemical oxidant-free conditions. A series of imidazo[1,5-a]quinazolin-5(4H)-ones and 5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carbonitriles can be obtained in high yields and the product distribution can be modulated by virtue of this method. The reaction mechanism was investigated and the corresponding intermediates were studied. The reaction features a broad substrate scope, regulation of the product distribution, mild conditions and scalable preparation. [ABSTRACT FROM AUTHOR]

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level. [ABSTRACT FROM AUTHOR]