A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds.

The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.

Theoretical exploration of the phenolic compounds' inhibition mechanism of heterocyclic aromatic amines in roasted beef patties by density functional theory.

The ability of spices (bay leaf, star anise, and red pepper) and their characteristic phenolic compounds (quercetin, kaempferol, and capsaicin) to inhibit Heterocyclic aromatic amines (HAAs) in roasted beef patties were compared. Density functional theory (DFT) was used to reveal phenolic compounds interacting with HAAs-related intermediates and free radicals to explore possible inhibitory mechanisms for HAAs. 3 % red chili and 0.03 % capsaicin reduced the total HAAs content by 57.09 % and 68.79 %, respectively. DFT demonstrated that this was due to the stronger interaction between capsaicin and the ß-carboline HAAs intermediate (Ebind = -32.95 kcal/mol). The interaction between quercetin and phenylacetaldehyde was found to be the strongest (Ebind = -17.47 kcal/mol). Additionally, DFT indicated that capsaicin reduced the carbonyl content by transferring hydrogen atoms (HAT) to eliminate HO·, HOO·, and carbon-centered alkyl radicals. This study provided a reference for the development of DFT in the control of HAAs.

Skeletal Editing: Ring Insertion for Direct Access to Heterocycles.

Skeleton editing has rapidly advanced as a synthetic methodology in recent years, significantly streamlining the synthesis process and gaining widespread acceptance in drug synthesis and development. This field encompasses diverse ring reactions, many of which exhibit immense potential in skeleton editing, facilitating the generation of novel ring skeletons. Notably, reactions that involve the cleavage of two distinct rings followed by the reformation of new rings through ring insertion play a pivotal role in the construction of novel ring skeletons. This article aims to compile and systematize this category of reactions, emphasizing the two primary reaction types and offering a thorough exploration of their associated complexities and challenges. Our endeavor is to furnish readers with comprehensive reaction strategies, igniting research interest and injecting fresh impetus into the advancement of this domain.

Synthesis, Structure and Antibacterial Activity of Two Novel Coordination Polymers Based on N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene and Heterocyclic Ligand against S. aureus.

As the use of antibiotics increases, the increasing resistance of bacteria is the main reason for the reduced efficiency of antibacterial drugs, making the research of new antibacterial materials become new hot spot. In this article, two novel coordination polymers (CPs), namely, [Cd2(L)2(bibp)2]n (1) and [Ni(L)(bib)]n (2), where H2L = N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene, bibp = 4,4'-bis(imidazol-1-yl)biphenyl, and bib = 1,3-bis(1-imidazoly)benzene, have been synthesized under solvothermal and hydrothermal condition. Structural clarification was performed through infrared spectrum and single-crystal X-ray diffraction analysis, while thermal analysis and XRD technology were used for the performance assessment of compounds 1 and 2. In addition, antibacterial performance experiments showed that compounds 1 and 2 have certain selectivity in their antibacterial properties and have good antibacterial properties against S. aureus. As the concentration of the compound increases, the inhibitory effect gradually strengthens, and when the concentration of the compound reaches 500 µg/mL and 400 µg/mL, the concentration of the S. aureus solution no longer increases and has been completely inhibited.

Applications of Pyrrole and Pyridine-based Heterocycles in Cancer Diagnosis and Treatment.

BACKGROUND: The escalation of cancer worldwide is one of the major causes of economy burden and loss of human resources. According to the American Cancer Society, there will be 1,958,310 new cancer cases and 609,820 projected cancer deaths in 2023 in the United States. It is projected that by 2040, the burden of global cancer is expected to rise to 29.5 million per year, causing a death toll of 16.4 million. The hemostasis regulation by cellular protein synthesis and their targeted degradation is required for normal cell growth. The imbalance in hemostasis causes unbridled growth in cells and results in cancer. The DNA of cells needs to be targeted by chemotherapeutic agents for cancer treatment, but at the same time, their efficacy and toxicity also need to be considered for successful treatment. OBJECTIVE: The objective of this study is to review the published work on pyrrole and pyridine, which have been prominent in the diagnosis and possess anticancer activity, to obtain some novel lead molecules of improved cancer therapeutic. METHODS: A literature search was carried out using different search engines, like Sci-finder, Elsevier, ScienceDirect, RSC etc., for small molecules based on pyrrole and pyridine helpful in diagnosis and inducing apoptosis in cancer cells. The research findings on the application of these compounds from 2018-2023 were reviewed on a variety of cell lines, such as breast cancer, liver cancer, epithelial cancer, etc. Results: In this review, the published small molecules, pyrrole and pyridine and their derivatives, which have roles in the diagnosis and treatment of cancers, were discussed to provide some insight into the structural features responsible for diagnosis and treatment. The analogues with the chromeno-furo-pyridine skeleton showed the highest anticancer activity against breast cancer. The compound 5-amino-N-(1-(pyridin-4- yl)ethylidene)-1H-pyrazole-4-carbohydrazides was highly potent against HEPG2 cancer cell. Redaporfin is used for the treatment of cholangiocarcinoma, biliary tract cancer, cisplatin-resistant head and neck squamous cell carcinoma, and pigmentation melanoma, and it is in clinical trials for phase II. These structural features present a high potential for designing novel anticancer agents for diagnosis and drug development. CONCLUSION: Therefore, the N- and C-substituted pyrrole and pyridine-based novel privileged small Nheterocyclic scaffolds are potential molecules used in the diagnosis and treatment of cancer. This review discusses the reports on the synthesis of such molecules during 2018-2023. The review mainly discusses various diagnostic techniques for cancer, which employ pyrrole and pyridine heterocyclic scaffolds. Furthermore, the anticancer activity of N- and C-substituted pyrrole and pyridine-based scaffolds has been described, which works against different cancer cell lines, such as MCF-7, A549, A2780, HepG2, MDA-MB-231, K562, HT- 29, Caco-2 cells, Hela, Huh-7, WSU-DLCL2, HCT-116, HBL-100, H23, HCC827, SKOV3, etc. This review will help the researchers to obtain a critical insight into the structural aspects of pyrrole and pyridine-based scaffolds useful in cancer diagnosis as well as treatment and design pathways to develop novel drugs in the future.

Studies on the Thermal Decomposition Course of Nitrogen-Rich Heterocyclic Esters as Potential Drug Candidates and Evaluation of Their Thermal Stability and Properties.

Drug candidates must undergo thermal evaluation as early as possible in the preclinical phase of drug development because undesirable changes in their structure and physicochemical properties may result in decreased pharmacological activity or enhanced toxicity. Hence, the detailed evaluation of nitrogen-rich heterocyclic esters as potential drug candidates, i.e., imidazolidinoannelated triazinylformic acid ethyl esters 1-3 (where R1 = 4-CH3 or 4-OCH3 or 4-Cl, and R2 = -COOC2H5) and imidazolidinoannelated triazinylacetic acid methyl esters 4-6 (where R1 = 4-CH3 or 4-OCH3 or 4-Cl, and R2 = -CH2COOCH3)-in terms of their melting points, melting enthalpy values, thermal stabilities, pyrolysis, and oxidative decomposition course-has been carried out, using the simultaneous thermal analysis methods (TG/DTG/DSC) coupled with spectroscopic techniques (FTIR and QMS). It was found that the melting process (documented as one sharp peak related to the solid-liquid phase transition) of the investigated esters proceeded without their thermal decomposition. It was confirmed that the melting points of the tested compounds increased in relation to R1 and R2 as follows: 2 (R1 = 4-OCH3; R2 = -COOC2H5) < 6 (R1 = 4-Cl; R2 = -CH2COOCH3) < 5 (R1 = 4-OCH3; R2 = -CH2COOCH3) < 3 (R1 = 4-Cl; R2 = -COOC2H5) < 1 (R1 = 4-CH3; R2 = -COOC2H5) < 4 (R1 = 4-CH3; R2 = -CH2COOCH3). All polynitrogenated heterocyclic esters proved to be thermally stable up to 250 °C in inert and oxidising conditions, although 1-3 were characterised by higher thermal stability compared to 4-6. The results confirmed that both the pyrolysis and the oxidative decomposition of heterocyclic ethyl formates/methyl acetates with para-substitutions at the phenyl moiety proceed according to the radical mechanism. In inert conditions, the pyrolysis process of the studied molecules occurred with the homolytic breaking of the C-C, C-N, and C-O bonds. This led to the emission of alcohol (ethanol in the case of 1-3 or methanol in the case of 4-6), NH3, HCN, HNCO, aldehydes, CO2, CH4, HCl, aromatics, and H2O. In turn, in the presence of air, cleavage of the C-C, C-N, and C-O bonds connected with some oxidation and combustion processes took place. This led to the emission of the corresponding alcohol depending on the analysed class of heterocyclic esters, NH3, HCN, HNCO, aldehydes, N2, NO/NO2, CO, CO2, HCl, aromatics, and H2O. Additionally, after some biological tests, it was proven that all nitrogen-rich heterocyclic esters-as potential drug candidates-are safe for erythrocytes, and some of them are able to protect red blood cells from oxidative stress-induced damage.

Acetylated galactopyranosyl N-heterocyclic monocarbene complexes of Silver(I) as novel anti-proliferative agents in a rhabdomyosarcoma cell line.

Herein, four silver(I) complexes bearing acetylated d-galactopyranoside-based N-heterocyclic carbene ligands were synthesized and fully characterized by elemental analysis, NMR, and X-ray photoelectron spectroscopy. All complexes were obtained with an anomeric ß-configuration and as monocarbene species. In this study, we investigated the biological effects of the silver(I) complexes 2a-d on the human rhabdomyosarcoma cell line, RD. Our results show concentration-dependent effects on cell density, growth inhibition, and activation of key signaling pathways such as Akt 1/2, ERK 1/2, and p38-MAPK, indicating their potential as anticancer agents. Notably, at 35.5 µM, the complexes induced mitochondrial network disruption, as observed with 2b and 2c, whereas with 2a, this disruption was accompanied by nuclear content release. These results provide insight into the utility of carbohydrate incorporated NHC complexes of silver(I) as new agents in cancer therapy.

Synthesis of Heterocyclic Ring-Fused Bisnoralcohol Derivatives as Novel Small-Molecule Antiosteoporosis Agents.

A series of heterocyclic ring-fused derivatives of bisnoralcohol (BA) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Most of these derivatives possessed potent antiosteoporosis activities in a dose-dependent manner. Among these compounds, 31 (SH442, IC50 = 0.052 µM) exhibited the highest potency, displaying 100% inhibition at 1.0 µM and 82.8% inhibition at an even lower concentration of 0.1 µM, which was much more potent than the lead compound BA (IC50 = 2.325 µM). Cytotoxicity tests suggested that the inhibitory effect of these compounds on RANKL-induced osteoclast differentiation did not result from their cytotoxicity. Mechanistic studies revealed that SH442 inhibited the expression of osteoclastogenesis-related marker genes and proteins, including TRAP, TRAF6, c-Fos, CTSK, and MMP9. Especially, SH442 could significantly attenuate bone loss of ovariectomy mouse in vivo. Therefore, these BA derivatives could be used as promising leads for the development of a new type of antiosteoporosis agent.

The magnetic layered double hydroxide/zeolitic imidazolate framework-8 nanocomposite coupled with HPLC-MS/MS for the detection of heterocyclic aromatic amines in thermally processed meat.

In this research, a novel magnetic nanocomposite (Fe3O4@Zn/Al-LABSA-LDH/ZIF-8) was synthesized using Fe3O4 as the magnetic core, layered double hydroxide (LDH) with linear alkylbenzene sulfonic acid (LABSA) intercalation and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Benefiting from the intercalation of LABSA into LDH combined with ZIF-8, the multiple interactions, including π-π stacking, hydrogen bonding, and electrostatic interactions, conferred high selectivity and good extraction capability to the material towards heterocyclic aromatic amines (HAAs). Fe3O4@Zn/Al-LABSA-LDH@ZIF-8 was used as an adsorbent for magnetic solid-phase extraction (MSPE) to enrich HAAs in thermally processed meat samples, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection. The method exhibited a low detection limit (0.021-0.221 ng/g), good linearity (R2 ≥ 0.9999), high precision (RSD < 7.2 %), and satisfactory sample recovery (89.7 % -107.5 %). This research provides a promising approach for developing novel adsorbents in sample preparation and improving analytical performance.

Sustainable and Safe N-alkylation of N-heterocycles by Propylene Carbonate under Neat Reaction Conditions.

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.

Indole as a Versatile Building Block in Cycloaddition Reactions: Synthesis of Diverse Heterocyclic Frameworks.

Indole, a ubiquitous and structurally versatile aromatic compound, has emerged as a key player in the synthesis of diverse heterocyclic frameworks via cycloaddition reactions. These reactions are completely atom-economical and, hence, are considered as green reactions. This review article provides a comprehensive overview of the pivotal role played by indole in the construction of complex and biologically relevant heterocyclic compounds. Here we explore the chemistry of indole-based cycloadditions, highlighting their synthetic utility in accessing a wide array of heterocyclic architectures, including cyclohepta[b]indoles, tetrahydrocarbazoles, tetrahydroindolo[3,2-c]quinoline, and indolines, among others. Additionally, we discuss the mechanistic insights that underpin these transformations, emphasizing the strategic importance of indole as a building block. The content of this article will certainly encourage the readers to explore more work in this area.

Antimicrobial, anticancer activities, molecular docking, and DFT/B3LYP/LANL2DZ analysis of heterocyclic cellulose derivative and their Cu-complexes.

In this study, novel Cu-complexes of heterocyclic cellulose which were synthesized via the reaction of carboxymethyl cellulose (CMC) from bagasse pulp with NH2NH2 to give hydrazide cellulose which easily reacted with CS2 to form salt and then cyclized in the presence of HCl to afford cellulose oxadiazole, or with hydrazine hydrate to give cellulose triazole. Furthermore, the cellulose oxadiazole and triazole moieties acting as chelating agents with metal ion Cu (II), and all synthesized compounds were examined for their spectral analysis to show the adsorption of Cu (II) on the surface of cellulose through intramolecular hydrogen bonding. Results illustrated that cellulose oxadiazole and Cu- cellulose oxadiazole exhibited antimicrobial activities more than triazole and Cu- cellulose triazole. Furthermore, anticancer results showed that both cellulose oxadiazole and triazole exhibited activity higher than Cu-cellulose oxadiazole and Cu-cellulose triazole, where the cellulose triazole showed the highest activity (IC50 = 58.7 µg/µL). Additionally, the docking simulation of the synthesized cellulose complexes with different proteins such as PDBID:3t88, PDBID:4ynt, PDBID:1tgh, PDBID:2wje, and PDBID:4hdq and shortage bond length to confirm the experimental results. Optimization of metal complexes utilized the DFT/B3LYP/LANL2DZ basis set to confirm the stability of these metals theoretically and their physical descriptors and FMO analysis.

Exploring the versatility of sulfur-containing heterocyclic metal complexes: Application in medical and prospects of visible-light-driven photocatalysis.

Numerous heterocyclic moieties serve as the foundational structure for clinically employed drugs, underscoring the significance of heterocycles in the innovation of pharmacologically active compounds. In the present investigation, a heterocyclic skeleton of thiophene-clubbed benzimidazole (tmb) was developed and utilized to synthesize seven novel series of metal (M(II) = Co, Ni, Cu, and Zn) complexes to explore diverse applications including pharmacological and photocatalytic performance. A sharp singlet peak appeared at 5.72 ppm (tmb) and 5.94 ppm for the Zn(II)-tmb complex corresponding to -CH2 protons, as evidenced by 1H NMR results, confirming the formation of targeted compounds. Antimicrobial assay and docking studies confirmed that the mixed metal complex; [Cu(tmb)2(1,10-phen)Cl2] possesses the highest activity and displayed significant biofilm inhibition, achieving 86.35 and 89.8% at concentrations of 1 and 0.020 mg/mL, respectively against E. coli. Furthermore, the photocatalytic activity was monitored by the degradation of methylene blue dye under direct sunlight and [Cu(tmb)2Cl2] exhibited a maximum degradation efficiency of 96.15% in 45 min. These findings could serve as inspiration for the development of benzimidazole-based metal complexes as effective anti-biofilm and photocatalytic agents.

Application and challenges of nitrogen heterocycles in PROTAC linker.

The absence of effective active pockets makes traditional molecularly targeted drug strategies ineffective against 80 % of human disease-related proteins. The PROTAC technology effectively makes up for the deficiency of traditional molecular targeted drugs, which produces drug activity by degrading rather than inhibiting the target protein. The degradation of PROTAC is not only affected by POI ligand and E3 ligand, but by the selection of suitable linker which can play an important role in the efficiency and selectivity of the degradation. In the early exploring stage of the PROTAC, flexible chains were priorly applied as the linker of PROTAC. Although PROTAC with flexible chains as linkers sometimes perform well in vitro bioactivity evaluations, the introduction of lipophilic flexible chains reduces the hydrophilicity of these molecules, resulting in generally poor pharmacokinetic characteristics and pharmacological activities in vivo. In addition, recent reports have also shown that some PROTAC with flexible chains have some risks to causing hemolysis in vivo. Therefore, PROTAC with flexible chains show less druggability and large difficulty to entering the clinical trial stage. On the other hand, the application of nitrogen heterocycles in the design of PROTAC linkers has been widely reported in recent years. More and more reports have shown that the introduction of nitrogen heterocycles in the linker not only can effectively improves the metabolism of PROTAC in vivo, but also can enhance the degradation efficiency and selectivity of PROTAC. These PROTAC with nitrogen heterocycle linkers have attracted much attention of pharmaceutical chemists. The introduction of nitrogen heterocycles in the linker deserves priority consideration in the primary design of the PROTAC based on various druggabilities including pharmacokinetic characteristics and pharmacological activity. In this work, we summarized the optimization process and progress of nitrogen heterocyclic rings as the PROTAC linker in recent years. However, there were still limited understanding of how to discover, design and optimize PROTAC. For example, the selection of the types of nitrogen heterocycles and the optimization sites of this linker are challenges for researchers, choosing between four to six-membered nitrogen heterocycles, selecting from saturated to unsaturated ones, and even optimizing the length and extension angle of the linker. There is a truly need for theoretical explanation and elucidation of the PROTAC to guide the developing of more effective and valuable PROTAC.

Novel saturated 1,2,4-trioxanes and their antimalarial activity against multidrug resistant Plasmodium yoelii nigeriensis in Swiss mice model via oral route.

Novel saturated 6-(4'-aryloxy phenyl) vinyl 1,2,4-trioxanes 12a(1-3)-12d(1-3) and 13a(1-3)-13d(1-3) have been designed and synthesized, in one single step from diimide reduction of 11a(1-3)-11d(1-3). All the newly synthesized trioxanes were evaluated for their antimalarial activity against multi-drug resistant Plasmodium yoelii nigeriensis via oral route. Cyclopentane-based trioxanes 12b1, 12c1 and 12d1, provided 100 % protection to the infected mice at 24 mg/kg × 4 days. The most active compound of the series, trioxane 12b1, provided 100 % protection even at 12 mg/kg × 4 days and 60 % protection at 6 mg/kg × 4 days. The currently used drug, ß-arteether provides only 20 % protection at 24 mg/kg × 4 days.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview.

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.

Tetrazole derivatives in the management of neurological disorders: Recent advances on synthesis and pharmacological aspects.

Neurological disorders are the leading cause of a large number of mortalities and morbidities. Nitrogen heterocyclic compounds have been pivotal in exhibiting wide array of therapeutic applications. Among them, tetrazole is a ubiquitous class of organic heterocyclic compounds that have attracted much attention because of its unique structural and chemical properties, and a wide range of pharmacological activities comprising anti-convulsant effect, antibiotic, anti-allergic, anti-hypertensive to name a few. Owing to significant chemical and biological properties, the present review aimed at highlighting the recent advances in tetrazole derivatives with special emphasis on their role in the management of neurological diseases. Besides, in-depth structure-activity relationships, molecular docking studies, and associated modes of action of tetrazole derivatives evident in in vitro, in vivo preclinical, and clinical studies have been discussed.

Heterocyclic fluorescent Schiff base chemosensors for the detection of Fe(III) and Cu(II) ions.

Two new Schiff bases were synthesized from 1-(2,4-dihydroxyphenyl)ethanone and pyridine derivatives. Both compounds were characterized using infrared, UV-Vis., 1H NMR, 13C NMR and mass spectral studies. Density functional theory (DFT) calculations were performed for both the Schiff bases with 6-31G(d, p) as the basis set. Vibrational frequencies calculated using the theoretical method were in good agreement with the experimental values. Both the Schiff bases were highly fluorescent in nature. The cation-recognizing profile of the compounds was investigated in aqueous methanol medium. The Schiff base 4-(1-(pyridin-4-ylimino)ethyl)benzene-1,3-diol (PYEB) was found to interact with Fe(III) and Cu(II) ions, whereas the Schiff base 4,4'-((pyridine-2,3-diylbis(azanylylidene))bis(ethan-1-yl-1-ylidene))bis(benzene-1,3-diol) (PDEB) was found to detect Cu(II) ions. The mechanism of recognition was established as combined excited state intramolecular proton transfer (ESIPT)-chelation-enhanced fluorescence (CHEF) effect and chelation-enhanced quenching (CHEQ) process for the detection of Fe(III) and Cu(II) ions, respectively. The stability constant of the metal complexes formed during the sensing process was determined. The limit of detection for Fe(III) and Cu(II) ions with respect to Schiff base PYEB was found to be 1.64 × 10-6 and 2.16 × 10-7 M, respectively. With respect to Schiff base PDEB, the limit of detection for Cu(II) ion was found to be 4.54 × 10-4 M. The Cu(II) ion sensing property of the Schiff base PDEB was applied in bioimaging studies for the detection of HeLa cells.

Defective UiO-66/cellulose nanocomposite aerogel for the adsorption of heterocyclic aromatic amines.

Heterocyclic aromatic amines (HAAs), arising as chemical derivatives during the high-temperature culinary treatment of proteinaceous comestibles, exhibit notable carcinogenic potential. In this paper, a composite aerogel (AGD-UiO-66) with high-capacity and fast adsorption of HAAs was made with anchoring defective UiO-66 (D-UiO-66) mediated by lauric acid on the backbone of cellulose nanofibers (CNF). AGD-UiO-66 with hierarchical porosity reduced the mass transfer efficiency for the adsorption of HAAs and achieved high adsorption amount (0.84-1.05 µmol/g) and fast adsorption (15 min). The isothermal adsorption model demonstrated that AGD-UiO-66 belonged to a multilayer adsorption mechanism for HAAs. Furthermore, AGD-UiO-66 was successfully used to adsorb 12 HAAs in different food (roasted beef, roasted pork, roasted salmon and marinade) with high recoveries of 94.65%-104.43%. The intrinsic potential of AGD-UiO-66 demonstrated that it could be widely applicable to the adsorption of HAAs in foods.

Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies.

The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.