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In this work, a novel ultrasound mediated synthesis of chromone based α-aminophosphonate using CdS/CNT nanocomposite has been reported. The nanocomposite was characterized using techniques like Fourier-Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction, Raman spectroscopy, Brunauer–Emmett–Teller (BET) analysis, and morphology studies were carried out using Field-Emission Scanning Electron Microscopy, and Transmission Electron Microscopy. Further, the synthesized α-aminophosphonate derivatives were characterized using FTIR, 1H-NMR and CHN elemental analysis. The present method provides various advantages such as operational simplicity, high yield, short reaction time, easy workup and solvent free condition. In addition, the catalyst exhibited remarkable reusability, demonstrating consistent performance up to five runs without any significant loss of its catalytic activity. The ICP-AES analysis suggested that there is no leaching of CdS from the surface of CNT. [ABSTRACT FROM AUTHOR]

A simple synthetic strategy to construction of novel 4-oxo-2-phenyl-4H-chromene-3-carbothioamides (2–6) was achieved. The synthetic strategy depended on the treatment of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (1) with some examples of aryl, aralkyl, aroyl and phosphorus isothiocyanates with promotion of DBU. The interesting 4,6-diphenyl-5-(2-hydroxy-benzoyl)-2-thioxo-3,4-dihydro-2H-1,3,4-oxazaphosphinine (8) as a highly regioselective product was obtained through treatment of the substrate 1 with phenyl phosphonisothiocyanatidous chloride whereas the other novel 2-phenyl-3-(2-thioxo-2H-1,3,5,4-thiadiazaphosphinin-6-yl)-4-oxo-4H-chromenes (9 and 10) were formed by using phosphorous diisothiocyanate and triisothiocyanate, respectively, under the same basic reaction conditions. All the reaction mechanisms were discussed. Structures of all the synthesized products were established by elemental analysis and available spectral tools. [ABSTRACT FROM AUTHOR]

This study investigated the in vivo efficacy of a chromium derivative extracted from date palms pit against Aedes aegypti the third instar larvae, the known vector of dengue fever in Saudi Arabia. Chromone 1, a flavonoid chromone component, was isolated from the alcoholic extract of date palm pits (DPP) using High‐performance liquid chromatography (HPLC). The results showed that exposure of A. aegypti larvae to whole DPP extract and chromone 1 for 24 h resulted in significant insecticidal efficacy with LC50 values of 132.82 and 54.64 ppm, respectively. The same concentrations also effectively inhibited AChE (acetylcholinesterase) activity up to −56.83 and −58.58%, respectively, compared to controls. The acetylcholine bromide test further confirmed the interaction between chromone 1 and AChE. The results also revealed that the chromone 1 treatment altered Deoxyribonucleic Acid (DNA) and protein content. It also exhibited that the extract of date palm pits DPP can effectively serve as sustainable ingredients for the control management of A. aegypti. [ABSTRACT FROM AUTHOR]

Chromone‐based compounds have established cytotoxic, antiproliferative, antimetastatic, and antiangiogenic effects on various cancer cell types via modulating different molecular targets. Herein, 17 novel chromone‐2‐carboxamide derivatives were synthesized and evaluated for their in vitro anticancer activity against 15 human cancer cell lines. Among the tested cell lines, MDA‐MB‐231, the triple‐negative breast cancer cell line, was found to be the most sensitive, where the N‐(2‐furylmethylene) (15) and the α‐methylated N‐benzyl (17) derivatives demonstrated the highest growth inhibition with GI50 values of 14.8 and 17.1 μM, respectively. In vitro mechanistic studies confirmed the significant roles of compounds 15 and 17 in the induction of apoptosis and suppression of EGFR, FGFR3, and VEGF protein levels in MDA‐MB‐231 cancer cells. Moreover, compound 15 exerted cell cycle arrest at both the G0‐G1 and G2‐M phases. The in vivo efficacy of compound 15 as an antitumor agent was further investigated in female mice bearing Solid Ehrlich Carcinoma. Notably, administration of compound 15 resulted in a marked decrease in both tumor weight and volume, accompanied by improvements in biochemical, hematological, histological, and immunohistochemical parameters that verified the repression of both angiogenesis and inflammation as additional Anticancer mechanisms. Moreover, the binding interactions of compounds 15 and 17 within the binding sites of all three target receptors (EGFR, FGFR3, and VEGF) were clearly illustrated using molecular docking. [ABSTRACT FROM AUTHOR]

An electrochemical decarboxylative addition of N‐substituted glycines to enaminones has been developed and conducted under oxidant‐, catalyst‐, and light‐free conditions in acetonitrile at room temperature by using electron as the traceless oxidant, which provided a green approach to access C3‐aminomethyl chromones. The resulting products were formed through radical addition/oxidation/cyclization or electrophilic addition/cyclization pathway and could act as valuable building blocks to construct polysubstituted pyrimidine derivatives. [ABSTRACT FROM AUTHOR]

The course of Alzheimer's disease (AD) is largely influenced by interleukin-6 (IL-6) and acetylcholinesterase (AChE). Therefore, concurrent suppression of these two targets is a rational approach for the development of anti-AD molecules. The study is aimed to design a molecule with pharmacophore capable of inhibiting both the targets. Four series are designed by coupling a chromone moiety (a pharmacophore that inhibits IL-6) with a N,N-disubstituted amine (that inhibits AChE) through a linker (1–4 carbon chain). The in silico studies on the designed compounds led to the identification of 16 best-fit compounds having good oral bioavailability and blood brain barrier permeability. All 16 compounds were synthesized and evaluated for anti-AChE activity. Six compounds showing >45 % inhibition of AChE at 1 μM concentration are further evaluated for BuChE (butyrylcholinesterase) and IL-6 inhibitory activities. Compound YS3g is the most potent inhibitor of EeAChE (IC50 = 0.45 μM) and of IL-6 (IC50 = 0.46 μM). Subsequently, it is found to show dose-dependent effects in STZ (streptozotocin)-induced memory deficit model at three doses (0.2, 0.4 and 0.8 mg/kg). At higher dose (0.8 mg/kg), it reverses the deficit as also supported by histopathological studies. The findings reveal that a chromone nucleus coupled with a piperazine via a three-carbon linker may be a useful template for developing novel moieties against AD.

A squaramide‐catalyzed asymmetric Michael/cyclization tandem reaction between 3‐hydroxychromenones and isatylidenemalononitriles was developed. Using this strategy, a wide scope of spiro[indoline‐3,4′‐pyrano[3,2‐b]chromene] derivatives, which combined chromone, pyran, indolone in one molecule, could be obtained in moderate to excellent yields (up to 94 %) with moderate enantioselectivities (up to 95 % ee). In addition, the scaled‐up experiment also confirmed the synthetic practicality of this synthetic strategy. [ABSTRACT FROM AUTHOR]

The novel chromonyltriazolo[3,4-b][1,3,4]thiadiazole derivative 5 was efficiently synthesized and utilized as key intermediate for construction of a diversity of heterocyclic rings; through reactions with binucleophilic reagents. Treating electron deficient substrate 5 with hydrazine hydrate, phenylhydrazine and hydroxylamine furnished pyrazolyl/isoxazolyltriazolo[3,4-b][1,3,4]thiadiazoles 6-8. Also, reacting substrate 5 with guanidine, cyanoguanidine and thiourea provided pyrimidinyltriazolo[3,4-b][1,3,4]thiadiazoles 9-11. Reaction of substrate 5 with ethylenediamine and o-phenylenediamine afforded diazepine derivatives 12 and 13. Reaction of substrate 5 with malononitrile, ethyl cyanoacetate and cyanoacetamide afforded pyrans 14, 15 and pyridine 16 linked triazolo[3,4-b][1,3,4]thiadiazolyl chromeno[2,3-b]pyridines. The anticancer efficiency of the current compounds presented diverse inhibitory action against certain cancer cell lines. On the basis of analytical and spectral findings, the structures of the synthesized products were confirmed. [ABSTRACT FROM AUTHOR]

Yupingfeng granules (YPFG) is commonly used in the treatment of immunological diseases, inflammations, and pulmonary diseases. Several studies have found that chromones, flavones, and saponins were the major bioactive compounds of YPFG. However, few studies have reported accurate quantification methods of these compounds. This study aimed to establish a simple and rapid method by using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to determine 15 bioactive compounds in YPFG. The experimental parameters including extraction methods, extraction solvents, extraction time, solid–liquid ratio, and LC–MS/MS condition were optimized. The linearity, precision, repeatability, stability, and recovery of the established method were evaluated. The contents of 15 bioactive compounds in seven batches of YPFG samples were analyzed by the established method and the results were compared with the values determined by HPLC. The optimal extraction condition was to extract 0.1 g of YPFG by ultrasound with 50 mL 50% ethanol for 30 min. A Waters ACQUITY UPLCBEH C18 column using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The linearity, precision, repeatability, stability, and recovery of the method were within acceptable ranges. Compared with HPLC analysis methods in Chinese Pharmacopoeia and literature, the established method was faster, simpler, more accurate, and more reliable. The method of simultaneous determination of 15 components in YPFG by LC–MS might provide a basis for the study of the bioactive compounds and the improvement of the quality standard of YPFG. [ABSTRACT FROM AUTHOR]

A new structurally simple fluorescent CP probe based on chromone was designed and synthesized, and its structure was fully characterized using various analytical techniques. The CP probe displays a high selectivity and sensitivity for sensing Fe3+ with a "turn-off" fluorescence response over other metal ions in a DMSO/H2O (4:1, v/v) solution. The experiment results show that the CP probe is stable over a wide pH range of 2.0–12.0. The detection limit for Fe3+ was calculated to be 0.044 μmol•L−1. The molar ratio method indicated that the binding mode between the CP probe and Fe3+ is a 1:1 complex formation. HR-MS and density functional theory (DFT) calculations were also performed to further confirm the recognition mechanism. Both fluorescence imaging experiments and the MTT assay demonstrated that the CP probe was suitable for detecting intracellular Fe3+ and no significant cytotoxicity in living cells. [ABSTRACT FROM AUTHOR]

Nerve agents are becoming serious issues for the healthy and sustainable environment of modern civilization. Therefore, its detection and degradation are of paramount importance to the scientific community. In the present contribution, we have introduced a chromo‐fluorogenic pyrene‐based probe, (E)‐2‐methoxy‐3‐(pyren‐1‐ylimino)‐3,8a‐dihydro‐2H‐chromen‐4‐ol (PMCO) to detect sarin stimulant diethylchlorophosphate (DCP) in solution and gaseous phases. On inserting DCP in PMCO solution, a visual colorimetric change from yellow to clear colourless in daylight and highly intensified blue fluorescence was observed instantly under a 365 nm portable UV lamp light. PMCO has outstanding selectivity and high sensitivity with a limit of detection of 1.32 μM in dimethyl sulfoxide (DMSO) medium and 77.5 nM in 20% H2O‐DMSO. A handy strained paper strip‐based experiment was demonstrated to recognize DCP in a mixture of similar toxic analytes. A dip‐stick experiment was performed to identify DCP vapour, and may be used as an effective photonic tool. We also demonstrated real sample analysis utilizing different DCP‐spiked water samples and validating DCP detection even in various types of soils such as sand, field, and mud. Therefore, this present study provides an effective chemosensor for instant and on‐site detection of toxic nerve agents in dangerous circumstances. [ABSTRACT FROM AUTHOR]

A series of 5-fluorouracil/coumarin and 5-fluorouracil/chromone hybrids were synthesized with good yields using click chemistry as the key step. The structures of these compounds and all intermediates were elucidated by spectroscopic analysis. Furthermore, pharmacokinetic and drug-like computations taken together indicated that the novel hybrids have a strong possibility to advance to further biological studies. [ABSTRACT FROM AUTHOR]

To clarify the chemical constituents of the traditional Chinese medicine Aloe made from Aloebarbadensis, i.e., the concentrated dry matter of the juice of the leaves of A.barbadensis, a systematic qualitative analysis of them was conducted using the technique of HPLC-DAD-ESI-IT-TOF-MSn in conjunction with the comparison of reference compounds and literature search. The gradient elution was performed with water (A)-acetonitrile (B) as mobile phase at a flow rate of 1.0 mL·min-1. The liquid chromatography-mass spectrometry data were acquired under alternate negative ion and positive ion detection mode using an ESI ion source. The structure elucidation of the chemical constituents was mainly based on negative ion mass spectrometry data. The results were as follows: (1) For the first time, the fragmentation pathways of anthraquinones (aloe-emodin, physcion, and emodin-8-O-β-D-glucoside), anthrones (aloin A, aloinoside A), chromones (aloeresin D, 7-O-methylaloeresin A, altechromone A, aloesin, aloeresin G, and aloeresin C), and α-pyranones (aloenin A, aloenin B) in Aloe made from A.barbadensis were clarified. The fragmentation pathway of anthraquinones was dominated by loss of CO2 and CO, and that of anthrones was dominated by cleavage of hexosides and loss of CO. The fragmentation pathways of chromones was dominated by cleavage of hexosides and hydrolysis of the ester group, and that of α-pyranones was dominated by cleavage of hexosides and loss of CO2 and H2O. (2) A total of 168 chemical constituents of Aloe made from A.barbadensis were detected, and 78 of them were identified on the basis of reference compound comparison, literature retrieval, and chemical database (such as SciFinder) searching. The 78 compounds included 3 anthraquinones, 29 anthrones, 35 chromones, 7 α-pyranones and 4 other constituents. Twenty-three of 78 compounds were discovered in the leaves of A.barbadensis for the first time. Fourteen of 23 were newly discovered compounds, including aloinoside D, isoeleutherin, and ethylidene-aloenin, possessed antibacterial, anti-inflammatory, or free radical scavenging activities. The results of this study further enrich the information on the chemical constituents of the traditional Chinese medicine Aloe made from A.barbadensis, and lay a foundation for the study of the therapeutic material basis and quality control methods of Aloe.

A preparative approach to thiazole-containing chromone derivatives has been developed by modifying the corresponding aldehydes with their further transformation into propenone derivatives, and finally introducing them into the Algar-Flynn-Oyamada reaction. Several methods for obtaining propenones have been analyzed, and the most effective and practically convenient one has been found. The thiazole-containing analogs of chromones obtained have a great potential as probes for a wide range of studies.

By the optimization of previously established pancreatic lipase (PL) inhibitory lead, we have developed novel chromone‐containing analogues with embedded acrylate fragment as potential PL inhibitors. The analogues were designed by considering the structural features required for binding at the active site of PL enzyme with the utilization of molecular docking study. An optimized synthetic scheme was utilized for the synthesis of designed analogues of prototypes 1&2. Through in vitro PL inhibitory screening, three analogues namely, 5fj, 5gj and 9a were identified as potent PL inhibitory leads with IC50 values of 4.92, 4.23 and 3.32 μM, respectively. The protein binding of analogue 9a was analysed by fluorescence quenching study and it was found to bind at one binding site with a binding constant of 1.93 × 105 L mol−1. Analogue 9a also exhibited a competitive inhibitory mechanism with Ki value of 1.601 μM. In future, the potent lead 9a can be optimized to get a comparable or more potential PL inhibitory activity than marketed drugs. [ABSTRACT FROM AUTHOR]

To clarify the chemical constituents of the traditional Chinese medicine Aloe made from Aloe barbadensis, i.e., the concentrated dry matter of the juice of the leaves of A. barbadensis, a systematic qualitative analysis of them was conducted using the technique of HPLC-DAD-ESI-IT-TOF-MSn in conjunction with the comparison of reference compounds and literature search. The gradient elution was performed with water (A)-acetonitrile (B) as mobile phase at a flow rate of 1.0 mL·min-1. The liquid chromatography-mass spectrometry data were acquired under alternate negative ion and positive ion detection mode using an ESI ion source. The structure elucidation of the chemical constituents was mainly based on negative ion mass spectrometry data. The results were as follows: (1) For the first time, the fragmentation pathways of anthraquinones (aloe-emodin, physcion, and emodin-8-O-β-D-glucoside), anthrones (aloin A, aloinoside A), chromones (aloeresin D, 7-O-methylaloeresin A, altechromone A, aloesin, aloeresin G, and aloeresin C), and α-pyranones (aloenin A, aloenin B) in Aloe made from A. barbadensis were clarified. The fragmentation pathway of anthraquinones was dominated by loss of CO2 and CO, and that of anthrones was dominated by cleavage of hexosides and loss of CO. The fragmentation pathways of chromones was dominated by cleavage of hexosides and hydrolysis of the ester group, and that of α-pyranones was dominated by cleavage of hexosides and loss of CO2 and H2O. (2) A total of 168 chemical constituents of Aloe made from A. barbadensis were detected, and 78 of them were identified on the basis of reference compound comparison, literature retrieval, and chemical database (such as SciFinder) searching. The 78 compounds included 3 anthraquinones, 29 anthrones, 35 chromones, 7 α-pyranones and 4 other constituents. Twenty-three of 78 compounds were discovered in the leaves of A. barbadensis for the first time. Fourteen of 23 were newly discovered compounds, including aloinoside D, isoeleutherin, and ethylidene-aloenin, possessed antibacterial, anti-inflammatory, or free radical scavenging activities. The results of this study further enrich the information on the chemical constituents of the traditional Chinese medicine Aloe made from A. barbadensis, and lay a foundation for the study of the therapeutic material basis and quality control methods of Aloe. [ABSTRACT FROM AUTHOR]

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. These compounds included selenium-substituted indole, coumarin, chromone, oxadiazole, imidazo[1,2-a]pyridine, Imidazo[2,1-b]thiazole, and oxazole, among others. These compounds were screened against Leishmania amazonensis promastigotes and intracellular amastigotes, and their cytotoxicity was assessed in peritoneal macrophages, NIH/3T3, and J774A.1 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes with reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM and 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in host cells (CC50 > 200 µM). Also, compounds MRK-107 and MRK-113 showed activity against intracellular amastigotes (IC50 18.31 and 15.93 µM and SI 12.55 and 10.92, respectively). In conclusion, the identified selenium-containing compounds hold potential structures as antileishmanial drug candidates to be further explored in subsequent studies. These findings represent a significant step toward the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments. [ABSTRACT FROM AUTHOR]

In recent years, lung cancer has become one of the most common malignant tumors in the world, which seriously threatens the life and health of mankind. Lung cancer is also the most common cancer in China. According to the latest report released by the National Cancer Center, the incidence and fatality rate of lung cancer in China rank first among malignant tumors, which has brought great disease burden to the Chinese. In this paper, using ethyl acetoacetate as the starting material, eight benzo[d]imidazolium[2,1-b]thiazole target compounds containing chromone were synthesized in five steps through alpha halogenation, cyclization, hydrolysis, condensation and cyclization reaction. MTT assay was used to evaluate the in vitro inhibitory activity of the target compounds on A549 and H2228 cancer cells. The IC50 values of the target compounds to A549 and H2228 cell lines ranged from 17.63 to 369.09 μmol/L. Some target compounds have moderate anti-tumor activity in vitro, which could be used to prepare related anti-tumor drugs for lung cancer. [ABSTRACT FROM AUTHOR]

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h showed potential IC50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC50 (9.8 µM) but lower potency than miltefosine IC50 (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC50 of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to LdCALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis. [ABSTRACT FROM AUTHOR]

An I2/PPh3‐mediated synthesis of 3‐thiolated chromones starting from 2‐hydroxyphenylenones and sodium sulfinates was reported. This method features one pot manner, metal‐free, easy performance, readily available starting materials and illustrating potential value for some biologically or pharmaceutically active compounds. In addition, a possible mechanism was proposed based on the control experiments. [ABSTRACT FROM AUTHOR]

A series of 5-fluorouracil/coumarin and 5-fluorouracil/chromone hybrids were synthesized with good yields using click chemistry as the key step. The structures of these compounds and all intermediates were elucidated by spectroscopic analysis. Furthermore, pharmacokinetic and drug-like computations taken together indicated that the novel hybrids have a strong possibility to advance to further biological studies.

ABSTRACT Candida species are the most common cause of fungal infections, and thus the emergence of antifungal-resistant species and biofilm formation by Candida further threatens the limited availability of antifungal agents. We investigated the antifungal and antibiofilm activities of 27 chromones against nine Candida species, including Candida albicans, Candida glabrata, Candida parapsilosis, and Candida auris. Four chromone-3-carbonitriles exhibited good antifungal activity with minimum inhibitory concentrations from 5 to 50 µg/mL and significantly inhibited biofilm formation by C. albicans. Furthermore, these four chromone-3-carbonitriles markedly inhibited cell aggregation and hypha formation, which are virulence factors and prerequisites for C. albicans biofilm formation. Transcriptomic analyses showed that the most active 6-bromochromone-3-carbonitrile downregulated the expressions of hypha-forming and biofilm-related genes (TEC1 and UME6) but upregulated the hyphal regulator UCF1. Toxicity assays conducted using plant and nematode models showed that the four chromone-3-carbonitriles were non-to-mildly toxic. This study suggests that chromones bearing the 3-carbonitrile motif should be considered potential antifungal agents against Candida species. IMPORTANCE The persistence of Candida infections is due to its ability to form biofilms that enable it to resist antifungals and host immune systems. Hence, inhibitions of the biofilm formation and virulence characteristics of Candida sp. provide potential means of addressing these infections. Among various chromone derivatives tested, four chromone-3-carbonitriles showed antifungal, antibiofilm, and antivirulence activities against several Candida species. Their mode of action has been partially revealed, and their toxicity is reported here using nematode and plant models.

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h showed potential IC50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC50 (9.8 µM) but lower potency than miltefosine IC50 (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC50 of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to LdCALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.

Abstract Inflammation is deemed to be a substantial and terrifying indicator of the advancement of diverse life‐threatening diseases. Regarding the preceding studies that assured the remarkable efficiency of chromone scaffolds and thiazolopyrimidine-based compounds as efficacious anti-inflammatory candidates, a new chromone-thiazolopyrimidine hybrid 3a–t was synthesized and investigated for their in vivo anti-inflammatory efficacy as well as their ulcerogenic effect. The majority of the examined candidates displayed a noticeable anti-inflammatory potency comparable to the standard drug (celecoxib), and interestingly, they exhibited no ulcerogenic effect. Moreover, the promising compounds 3a, 3c, 3i, and 3 l were assessed for their inhibitory properties against the production of various inflammatory mediators (TNF-α, IL-6, and PGE2). They demonstrated a noteworthy suppression efficiency on the emission of TNF-α, IL-6 and PGE2 (TNF-α level range 52.30-63.56 pg/mL, IL-6 level range 165.44–177.17 pg/mL, PGE2 level range 38.46–47.21 pg/mL) relative to celecoxib (49.77, 164.49, and 37.50 pg/mL, respectively). Additionally, the molecular docking studies for the bioactive derivatives 3a, 3c, 3i, and 3l were accomplished to determine the interaction forms inside the binding sites of the inflammatory mediators TNF-α, IL-6, and mPGES-1. The screened receptors exhibited essential binding interactions with the chromone and the 3-oxothiazolo[3,2-a]pyrimidine scaffolds. Finally, ADME investigations of the latter derivatives portended their significant oral bioavailability and GI absorption. [ABSTRACT FROM AUTHOR]

This review summarizes information about the chemical composition and beneficial properties of species of the genus Eranthis Salisb. from the world's flora. To date, seven out of ~14 species found in Asia and parts of Europe have been studied to various degrees. Here, data are presented on the diversity of sets of chromones, furochromones, triterpene saponins, coumarins, and other classes of secondary metabolites of Eranthis species according to the literature. For new compounds—isolated from Eranthis for the first time—structural formulas are also provided. Among the new compounds, chromones and coumarins predominate, as do triterpene saponins of the olean and cycloartane series and lectin. The results of pharmacological studies are presented showing anti-inflammatory, antioxidant, antiviral, and other types of biological activities found in extracts, in their fractions, and in individual compounds of the aboveground and underground organs and parts of Eranthis species. Despite the limited geographic range of Eranthis plants, it is possible to search for active substances, develop methods for biological and chemical synthesis of the isolated substances, and create a finished therapeutic substance based on them. In addition, it is feasible to obtain the desired standardized pure materials from Eranthis species grown in vitro. [ABSTRACT FROM AUTHOR]

One chromone (1), together with four known alkaloids, were isolated from the mangrove endophytic fungus Aspergillus sp. ZJ-68. Their structures were elucidated by a combination of HRESIMS and NMR spectroscopic analyses. Compound 1 showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 4.094 ± 0.8 μM, which was better than positive drug indomethacin (IC50=35.8 ± 0.5 μM). [ABSTRACT FROM AUTHOR]

A preparative approach to thiazole-containing chromone derivatives has been developed by modifying the corresponding aldehydes with their further transformation into propenone derivatives, and finally introducing them into the Algar-FlynnOyamada reaction. Several methods for obtaining propenones have been analyzed, and the most effective and practically convenient one has been found. The thiazole-containing analogs of chromones obtained have a great potential as probes for a wide range of studies. [ABSTRACT FROM AUTHOR]

A new structurally simple fluorescent CP probe based on chromone was designed and synthesized, and its structure was fully characterized using various analytical techniques. The CP probe displays a high selectivity and sensitivity for sensing Fe3+ with a “turn-off” fluorescence response over other metal ions in a DMSO/H2O (4:1, v/v) solution. The experiment results show that the CP probe is stable over a wide pH range of 2.0–12.0. The detection limit for Fe3+ was calculated to be 0.044 μmol•L−1. The molar ratio method indicated that the binding mode between the CP probe and Fe3+ is a 1:1 complex formation. HR-MS and density functional theory (DFT) calculations were also performed to further confirm the recognition mechanism. Both fluorescence imaging experiments and the MTT assay demonstrated that the CP probe was suitable for detecting intracellular Fe3+ and no significant cytotoxicity in living cells.

A series of chromone-thiazolidine-2,4-dione derivatives (e1 ∼ 28) were synthesized and screened for their α-glucosidase inhibitory. All synthetic derivatives presented excellent α-glucosidase inhibitory with IC50 values ranging from 2.40 ± 0.11 to 5.66 ± 0.15 μM, comparing to positive control acarbose (IC50 value: 640.57 ± 5.13 μM). Among them, compound e28 displayed the strongest α-glucosidase inhibitory (IC50 value: 2.40 ± 0.11), ∼267 times stronger than positive control acarbose. Kinetic studies revealed that compound e28 was a reversible non-competitive inhibitor. CD spectra and 3D fluorescence spectra results explained that compound e28 changed the conformational changes of α-glucosidase. Molecular docking simulated the binding between compound e28 and α-glucosidase. In vitro cytotoxicity assay ascertained the good security of e28.

An approach to the preparation of hereto unknown parent 5- and 7-azachromones was developed. The key step relied on the NaHmediated condensation of isomeric 2(4)-acetyl-3-hydroxypyridines (obtained from isomeric 3-hydroxypyridine carboxylic acids) with ethyl formate. Physicochemical studies revealed that no significant changes in lipophilicity and slightly higher basicity values were observed upon introduction of the nitrogen atom into the parent chromone; therefore, 5- and 7-azachromones can be used as direct analogs of this classical heterocyclic fragment. The synthetic utility of azachromones was demonstrated by the preparation of a series of 3,4-dihydro-2H-pyrano[3,2-b]pyridines and -[2,3-c]pyridines. The catalytic hydrogenation of the pyranone ring of azachromones was performed for the selective preparation of isomeric azachromanols, which could be oxidized with MnO2 (to azachromanones) or involved into Barton–McCombie deoxygenation (for the synthesis of the non-substituted derivatives). [ABSTRACT FROM AUTHOR]

Literature evidence that natural products are potential bioactive components for lead compounds in drug discovery. These molecules have distinctive chemical structures that play a significant role in identifying and developing drugs for different diseases as therapeutics. Further, natural products have been known for both medicinal and biological activities. One such natural product, luteolin, a wonder molecule, belongs to the class of flavonoids. A dietary flavonoid, luteolin exhibits potent anticancer, antioxidant, anti-inflammatory, and antiviral activities. This review covers comprehensive insight into the anticancer potential and structural activity relationship of luteolin and its analogs. This review also summarizes the recent reports on anticancer activities of luteolin and our earlier work on target-specific p300 inhibitory potential of luteolin and its mimics. [ABSTRACT FROM AUTHOR]

A selective chromone‐containing colorimetric chemosensor DOCC ((E)‐N,N‐dimethyl‐2‐((4‐oxo‐4H‐chromen‐3‐yl)methylene)hydr azine‐1‐carbothioamide) was designed for the sequential probing of Cu2+ and cysteine. DOCC exhibited a marked color variation from colorless to pale yellow and had the lowest limit of detection (0.30 μM) among the chromone‐based colorimetric sensors for Cu2+ in near‐perfect aqueous media. DOCC could work to probe and quantify Cu2+ in real water samples with great recovery (98‐102%). DOCC could discriminate Cu2+ using the test kit down to 10 μM. On the other hand, Cu2+‐2⋅DOCC could selectively detect cysteine (Cys) in a sequential step through the demetallation reaction. Cu2+‐2⋅DOCC showed that its color returned from pale yellow to colorless only in the presence of Cys and its limit of detection was calculated to be 6.62 μM. The practical applications for Cys were successfully achieved in water samples with perfect recovery (99–100%) and pH tests at 7–9. FT‐IR, Job plot, ESI‐MS, and DFT calculations were applied to explain the sensing mechanisms of Cu2+ by DOCC and Cys by Cu2+‐2⋅DOCC. [ABSTRACT FROM AUTHOR]

Chromone has emerged as one of the most important synthetic scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and synthesised, in order to discover promising anti-breast tumour candidates. Almost all target derivatives showed antiproliferative activity against MCF-7 and MDA-MB-231 cell lines. In particular, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed the most potent antiproliferative activity with IC50 values of 1.83 and 1.90 μM, respectively, and it also exhibited certain selectivity between tumour cells and normal cells. Further mechanism exploration against MDA-MB-231 cells showed that it possibly induced G2/M phase arrest and apoptosis by generating intracellular ROS and activating DNA damage. In addition, it also inhibited MDA-MB-231 cells metastasis, invasion and adhesion. Overall, methyl (S)-3-(4-(bis(2-chloroethyl)amino)phenyl)-2-(5-(((6-methoxy-4-oxo-4H-chromen-3-yl)methyl)amino)-5-oxopentanamido)propanoate showed potent antitumor activities and relatively low side effects, and deserved further investigation.

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a–d against normal HEK-293 cells were in the range of 102.4–293.2 μM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 μM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a–d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis. [ABSTRACT FROM AUTHOR]

The present work is directed to synthesize and evaluate the antimicrobial activity of some novel 2-heteroarylchromeno[2,3-d]pyrimidines. 2-(6,8-Dimethylchromon-3-yl)-8-methoxy-4H-chromeno[2,3-d]pyrimidine-4,5(3H)-dione (4) was successfully synthesized and utilized as a building block to produce a variety of heterocyclic compounds. 2-(4-Pyrazolyl/isoxazolyl)chromeno[2,3-d]pyrimidines 5–7 were obtained from the reaction of compound 4 with hydrazine hydrate, phenylhydrazine, and hydroxylamine, respectively. Also, 2-(6-pyrimidinyl)chromeno[2,3-d]pyrimidines 8–12 were efficiently prepared from reacting compound 4 with guanidine, cyanoguanidine, thiourea, acetamidine, and benzamidine, respectively. Further, chromeno[2,3-d]pyrimidines linked diazepine 13, benzodiazepine 14, benzoxazepine 15 and benzothiazepine 16 were also synthesized. The synthesized compounds were examined for their antimicrobial efficiency. Pyrazolylchromeno[2,3-d]pyrimidines 5 and 6 showed the best activity against all kinds of microorganisms. Structures of the synthesized compounds were validated using analytical and spectral data. [ABSTRACT FROM AUTHOR]

This study described the bioactivity and the structure-activity relationship (SAR) of newly synthesized chromone derivatives against triple-negative breast cancer (TNBC) MDA-MB-231 cells. Among the compounds tested, C8 exerted a growth inhibitory effect on the TNBC-derived MDA-MB-231 cells with an IC50 value of 11.71 ± 0.79 µM. Results showed that it could promote apoptosis, sensitize TNBC MDA-MB-231 cells to doxorubicin (Dox) and inhibit multiple kinase activities with higher selectivity against PIM1 and PIM2 kinases. Molecular docking results revealed compound C8 engaged in several critical interactions with the important residues in PIM1 and PIM2 binding sites. This suggests that compound C8 possessed anticancer activity on TNBC cells potentially mediated by inhibition of multiple tyrosine kinases and kinases involved in cell-cycle regulation. [ABSTRACT FROM AUTHOR]

The development of quick and precise detection technologies for active compounds in vivo is critical for disease prevention, diagnosis and pathological investigation. The fluorescence signal of the fluorophore usually defines the probe's sensitivity to the chemical being examined. Many natural compounds containing flavone and isoflavone scaffolds exhibit a certain amount fluorescence, albeit with poor fluorescence quantum yields. Therefore, we used density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations to investigate the fluorescence characteristics of chromium-derived fluorophores in more depth. Different substituents are introduced at different positions of the chromone. As weak electron donor groups, alkyl and aromatic groups were discovered to have varying quantum yields on the fluorophore scaffold, and longer alkyl chains are favorable to enhance fluorescence quantum yield. In comparison to the amino group, substituted amino group can avoid group rotation, and the introduction of cyclic amines such as pyrrolidine and heterocyclic amines can improve optical characteristics. The electron-donating methoxy group at position 6 helps to increase the fluorescence quantum yield. [ABSTRACT FROM AUTHOR]

Forced intercalation (FIT) probes have proven to be a reliable, rapid, inexpensive, and accurate method for the detection and visualization of specific nucleic acid sequences. The accommodation of a rationally designed chromone-based fluorogen within a double-stranded DNA structure was investigated by UV–Vis spectrophotometry and steady-state fluorescence spectroscopy under physiological pH conditions. After selective excitation matching with a 350 nm laser, the intrinsically negligible fluorescence of the tethered electroneutral label in a single-stranded context was increased 10-fold upon duplex formation. This fluorescence enhancement was also accompanied by a mega-Stokes shift (~100 nm) that placed the emission in the cyan color range; both features are appreciable for bio-imaging purposes. In sum, its fluorogenic behavior and its marginal impact on the double helix make this dye a prospective tool for selectively sensing sequences of interest with a remarkable ON/OFF contrast. [ABSTRACT FROM AUTHOR]

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. These compounds included selenium-substituted indole, coumarin, chromone, oxadiazole, imidazo[1,2-a]pyridine, Imidazo[2,1-b]thiazole, and oxazole, among others. These compounds were screened against Leishmania amazonensis promastigotes and intracellular amastigotes, and their cytotoxicity was assessed in peritoneal macrophages, NIH/3T3, and J774A.1 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes with reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM and 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in host cells (CC50 > 200 µM). Also, compounds MRK-107 and MRK-113 showed activity against intracellular amastigotes (IC50 18.31 and 15.93 µM and SI 12.55 and 10.92, respectively). In conclusion, the identified selenium-containing compounds hold potential structures as antileishmanial drug candidates to be further explored in subsequent studies. These findings represent a significant step toward the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

A chromone‐based Michael reaction using water as solvent and nucleophile was firstly developed to derivatize chromone via a multicomponent reaction (MCR) cascade sequence in absence of metal catalyst. A series of versatile enaminodiones was synthesized and further successfully transferred into two different pyrazoles with the same starting material under facile and mild condition by a pH control of the preferred isomer. [ABSTRACT FROM AUTHOR]

A chromone was isolated from alcoholic extracts from Bomarea setacea and identified as 2‐henicosyl‐5,7‐dihydroxy‐4H‐chromen‐4‐one. The leishmanicidal activity was evaluated against intracellular amastigotes of L. panamensis and cytotoxicity on U‐937 cells, maintained in standard culture conditions. This compound showed leishmanicidal activity (EC50=14.8±1.9 μg/mL, 31.4 μM), low cytotoxicity (LC50=>200 μg/mL, >423.7 μM). Additionally, this compound showed high antioxidant activity through ORAC and DPPH methods. These experimental results motivated us to carry out computational explorations such as docking against several parasite protein targets, molecular dynamics to validate docking results and DFT calculations, used to explain the high antioxidant activity of chromone. Notably, the docking results showed the N‐myristoyltransferase (NMT) enzyme to be a potential target for chromone (docking score −9.1 kcal.mol−1). Molecular dynamics (MD) studies provide strong evidence of the conformational stability of the chromone‐LpNMT complex obtained from docking throughout 50 ns all‐atom MD simulation. Molecular mechanics Poisson‐Boltzmann surface area (MM‐PBSA) analyses of chromone‐LpNMT complex show that the interaction between the ligand and the target protein is stable. DFT calculations allow to explain the greater in vitro antioxidant properties, and drug‐likeness studies show suitable pharmacokinetics properties for chromone. Our findings suggest that chromone has great potential to continue in the search for new drugs to treat leishmaniasis. [ABSTRACT FROM AUTHOR]

• The reactivity of substrate 3 was investigated towards binucleophiles. • Chromone moieties are more reactive than α,β-unsaturated ketone segment. • DFT/B3LYP/6-311G++(d,p) was used to discuss theoretical calculations. • ADME analysis and molecular docking studies were assessed. • The NMR were estimated theoretically and well-matched with experimental results. The electron deficient centers in α,β-unsaturated ketone 3 are C-2 and C=O of chromone moieties as well as C=O and H-β of α,β-unsaturated ketone segment. To investigate the reactivity of various electron deficient centers and to synthesize some heterocyclic systems, compound 3 was allowed to react with some binucleophilic reagents. The antimicrobial activity of some compounds showed a notable inhibitory effect on the microorganisms that were being studied. The synthesized compounds were verified by spectral and analytical data. The structure of the prepared compounds were optimized at the DFT/B3LYP level of theory employing 6-311G(d,p). Density Functional Theory (DFT) was used to compute the chemical reactivity descriptors. Compound 9 is more stable and less reactive than other compounds. MEP mapping was applied at the same computational level to identify the favored locations for electrophilic and nucleophilic assault, providing additional insight into the regioselectivity in the desired reaction. Moreover, the most reactive sites of compound 3 were investigated by Fukui function descriptor using Mulliken charges. The 13C and 1H-NMR spectra of the prepared compound were measured experimentally in DMSO, and correlated with the theoretical calculations that performed by 6-311G(d,p) of DFT-B3LYP method. All compounds met Veber's and Lipinski's requirements according to in silico predictions made with the SwissADME online server, suggesting the possibility for usage as oral active drugs. The synthesized compounds were also subjected to molecular docking studies to investigate their binding pattern and affinity for the CDKs active site and correlated with antimicrobial data. [ABSTRACT FROM AUTHOR]

• New chromone-isoxazole hybrids heterocycles have been successfully using multistep reactions. • The structures of the hybrids have been well characterized using spectroscopic techniques. • In vitro antibacterial tests have shown promising responses for the hybrids. • Computational studies have been assessed for the hybrids using molecular docking and ADMET profiling. A series of novel hybrid heterocycles incorporating isoxazole rings have been successfully synthesized, characterized, and evaluated for their antibacterial responses. The synthesized compounds were obtained by a subsequent N-alkylation and 1,3-dipolar cycloaddition reactions, their structures were identified by spectroscopy techniques (1H NMR, 13C NMR and 2D HSQC), and confirmed by mass spectrometry (HRMS). The spectroscopic data also show that the 1,3-dipolar cycloaddition (1,3-DC) reactions proceed in a regiospecific manner to give only one cycloadduct. The observed regioselectivity and the mechanistic study of the 1,3-DC reaction were further highlighted and explained using Density Functional Theory (DFT) calculations with the B3LYP/6–31G(d,p) basis set and Electron Localization Function (ELF) analysis. Moreover, the antibacterial screening shows that some compounds exhibit good efficacy against the tested bacterial strains. In addition, molecular docking studies were carried out to highlight the modes of interaction between the most active molecule 5d and receptors of Escherichia coli, Pseudomonas aeruginosa , and Staphylococcus aureus strains. The results show that the studied compound was effectively docked to the active sites of each responsible protein with high protein-binding energies in kcal/mol. Finally, the prediction of ADMET properties suggests that almost all the hybrid compounds have good pharmacokinetic profiles, with no observed signs of toxicity, except for compounds 5e, 5f and 5 g. [ABSTRACT FROM AUTHOR]

[Display omitted] • The fluorescent probe we reported here is the first example with highly selective and sensitive response to ONOO− in plants. • The probe can image endogenous and exogenous ONOO− in Arabidopsis thaliana root besides HeLa cell. • The probe has good water solubility. • A novel chromone-based fluorescence probe related with natural products was synthesized by facile route. As a typical reactive nitrogen species, peroxynitrite (ONOO−) plays an important role in cells and organisms. But in plants, information on the role of endogenous ONOO− remains limited. In order to explore its functions, it is necessary to probe ONOO− in biological systems, especially in plants. In this paper, we report RAW-A , a chromone-based fluorescence probe, exhibits a highly selective and sensitive response to ONOO−. It is worth noting that RAW-A has good water solubility, which is beneficial for the application of biological systems. RAW-A can respond to ONOO− even at low concentrations of ONOO−, indicating that the probe is expected to monitor ONOO− in real-time in living systems. In addition, confocal imaging experiments show that RAW-A can image endogenous and exogenous ONOO− in Arabidopsis thaliana root besides HeLa cell. It shows that RAW-A has the potential to be an imaging tool for studying the biological roles of ONOO− in plants. To our knowledge, RAW-A is the first fluorescent probe with highly selective and sensitive response to ONOO− in plants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel chromone-TZD hybrids were designed, synthesized as Bcl-2 inhibitors. • Compound 8l was found to be active against A549 cell line with an IC 50 of 6.1 µM. • ROS, staining assays, cell cycle analysis was performed, evidencing the apoptosis. • Reduced expression of Bcl-2 was observed with 79.1 % at 9 µM for compound 8l. • In-silico docking study also supports the apoptotic nature of designed molecules. Overexpression of Bcl-2 protein is a predominant hallmark of disturbed apoptotic pathway in most of the cancers. Herein, chromone-linked thiazolidinediones were designed and synthesized to target Bcl-2 for regulating anti-apoptotic proteins. The study on in vitro cancer cell lines revealed the presence of compounds 8a , 8k , 8l , and 8n , which were found to have good to moderate anti-proliferative activity (with an IC 50 concentration less than 10 µM). Among them, 8l depicted the highest cytotoxicity on the A549 cell line with an IC 50 of 6.1 ± 0.02 µM. Aberrantly, the compounds displayed less toxicity towards human embryonic kidney HEK cells underlining its selectivity. The DCFDA study revealed a gradual increase in the ROS generation of 8l , followed by its quantification by flow analysis. Similarly, the studies including DAPI, AO/EtBr and Annexin-V binding clearly elucidated the DNA damage, membrane integrity prospects, and insights for early and late apoptotic phases. Markedly, the Bcl-2-FITC anti-body study revealed that compound 8l reduced the expression of anti-apoptotic proteins by 79.1 % compared to the control at 9 µM concentration. In addition, the molecular docking study provided the impending scope of these hybrids, showing promising interaction with the Mcl-1 target (member of the Bcl-2 family) with comparable binding affinities. [ABSTRACT FROM AUTHOR]

This review summarizes information about the chemical composition and beneficial properties of species of the genus Eranthis Salisb. from the world’s flora. To date, seven out of ~14 species found in Asia and parts of Europe have been studied to various degrees. Here, data are presented on the diversity of sets of chromones, furochromones, triterpene saponins, coumarins, and other classes of secondary metabolites of Eranthis species according to the literature. For new compounds—isolated from Eranthis for the first time—structural formulas are also provided. Among the new compounds, chromones and coumarins predominate, as do triterpene saponins of the olean and cycloartane series and lectin. The results of pharmacological studies are presented showing anti-inflammatory, antioxidant, antiviral, and other types of biological activities found in extracts, in their fractions, and in individual compounds of the aboveground and underground organs and parts of Eranthis species. Despite the limited geographic range of Eranthis plants, it is possible to search for active substances, develop methods for biological and chemical synthesis of the isolated substances, and create a finished therapeutic substance based on them. In addition, it is feasible to obtain the desired standardized pure materials from Eranthis species grown in vitro.

OBJECTIVE: Proteostasis is an important process occurring in all living cells and is highly indispensable for cell survival. The HslVU protease/chaperone complex’s critical role in regulating proteostasis to maintain a healthy cellular proteome and its presence in pathogenic microbes made it an important drug target. This study aimed to identify small molecular inhibitors of the HslV protease. MATERIALS AND METHODS: Herein, a library of small molecules belonging to the triazine and chromone families has been evaluated for their inhibitory potential against the E. coli HslV protease using both in silico and in vitro techniques. RESULTS: Four compounds, i.e., SHS-II-123a, SHS-II-147a, US-IV-89, and US-IV-92, were identified as potential inhibitors of the HslV protease having IC50 values in the range of 0.1 to 0.32 μM. Additionally, these compounds’ drug-likeness and ADMET profiles indicated their compatibility to be considered safer drug candidates. CONCLUSIONS: To the best of our knowledge, this is the first report on small molecules having inhibitory effects on the HslVU complex. These identified compounds can be efficiently subjected to further investigations to develop novel and safer antimicrobial agents. [ABSTRACT FROM AUTHOR]

New calix[4]arene derivatives based on chromone linked through a thiosemicarbazone bridge have been designed and synthesized. It has been determined by UV‐visible absorption and IR‐spectroscopic study that molecular receptors are efficient for recognition of cations (Co2+, Cu2+, Ni2+ and Zn2+) and anions (F− and CN−), because calixarene plays a role as a molecular platform and the interaction is explained by the presence of the thiosemicarbazone bridge bound to chromone. The sensors showed selective colorimetric changes with cobalt (II), copper (II), cyanide and fluoride ions. The detection limits of 0.19 to 0.70 mg L−1 and the association constants ranging between 1.28×104 and 9.87×104 mol−1L can be estimated for these three sensors. [ABSTRACT FROM AUTHOR]