The present study focused on the synthesis, comprehensive structural elucidation, and detailed physicochemical characterization of two novel metal complexes, Cu(QHC) and Cd(QHC), derived from the newly synthesized ligand, 2-((4-oxo-1,4-dihydroquinolin-3-yl) methylene)hydrazine-1-carbothioamide (QHC). A variety of analytical techniques were employed, including elemental analysis, UV-Vis, FT-IR, mass, 1H NMR, 13C NMR, DEPT-45, 90 and 138 spectra, molar conductivity, magnetic susceptibility measurements, ESR, TEM and thermal analysis. The spectroscopic and analytical data revealed that coordination occurred through the nitrogen and sulfur donor atoms of the neutral bidentate QHC ligand, leading to the formation of mononuclear chelates with tetrahedral geometry. Transmission electron microscopy (TEM) analysis revealed that the Cu(QHC) complex exhibited a nanospherical morphology with aggregated structures forming compact clusters, whereas the Cd(QHC) complex displayed a nanorod-like morphology. The cytotoxic effects of the QHC ligand and its Cu(II) and Cd(II) complexes were investigated in vitro against three human cancer cell lines: A549, HeLa, and MDA-MB-231 using the sulforhodamine B (SRB) assay. Notably, the Cd(QHC) complex demonstrated significant potent cytotoxicity in comparison with doxorubicin and cis-platin. Additionally, the cytotoxicity was evaluated against healthy human cells HFB-4, where the complexes exhibited significantly high IC50 values, indicating their relative safety as potential anticancer agents. Further, the apoptotic analysis indicated that Cd(QHC) nanocomplex significantly induced late-stage apoptosis in the tested cancer cell lines. Additionally, cell cycle distribution revealed that this complex effectively arrested cell proliferation at the G1, S, and G2 phases. The Density Functional Theory (DFT) calculations were conducted to optimize the molecular geometries and determine key quantum chemical descriptors. In addition, drug-likeness and ADMET profiling were performed to evaluate the bioavailability and toxicity of the synthesized compounds. Molecular docking studies were also performed to explore the binding affinity of the synthesized compounds toward the active site of 4ASD VEGFR protein, supporting the experimental anticancer findings.

An efficient method was developed for the synthesis of eight novel functionalized 1,2,4,3-triazaphospholes and one 1,3,2-thiazaphosphinine incorporating a coumarin ring. Additionally, two interesting examples of diethyl coumarinyl phosphonate and diethyl chromeno-[3,4-c][1,2,4]triazolo[4,3-a]pyridinyl phosphonate were obtained. The proposed methodology involved the treatment of N'-benzoyl-2-oxo-2H-chromene-3-carbohydrazonamide (2) with various phosphorus agents, including phosphorus halides, phosphorus triamide, phosphorus esters, and phosphorus sulfides. IR, NMR, and mass spectrometric methods were used to confirm the structures of the prepared compounds. The antiproliferative properties of the isolated compounds were screened against HepG-2, MCF-7, and A549 cancer cells. The products 5, 7, 9, and 10 exhibited excellent cytotoxic properties compared with doxorubicin. These four bioactive compounds have low toxicity in healthy human HFB4 cells.

One-pot synthetic strategy was designed for the synthesis of novel diethyl (pyrazolo- [4,3-c]quinolin-3-yl)phosphonates and diethyl (isoxazolo[4,5-c]quinolin-3-yl)phosphonate. The novel phosphorus heterocycles of types 1,4,2-diazaphospholes, 1,4,2-oxazaphosphinines and 1,4,2-diazaphosphinines containing 4-quinolinone ring were also achieved. The designed strategies depended on a three component reaction of 4-oxo-1,4-dihydroquinoline-3-carboxaldehyde (1) with a series of bi-nucleophilic nitrogen reagents in the presence of diethyl phosphite under solvent-free and catalyst-free conditions. This newly developed approach helped to synthesize new ten organophosphorus compounds with good yields. The IR, MS and NMR spectroscopic tools were used to characterize the isolated compounds, and their formation mechanisms were discussed. All synthesized compounds were evaluated for their in vitro cytotoxicity against A549, MDA-MB-231 and HeLa cell lines. Compounds 10 and 11 exhibited the most potent cytotoxicity, in comparison with doxorubicin. Furthermore, these two compounds significantly induced early apoptosis and reducing cell viability in the studied tumor cells. Additionally, both compounds 10 and 11 demonstrated promising ability to arrest the cell cycle at the S and G2 phases. In silico ADMET predictions indicated that compounds 10 and 11 possess higher predicted human intestinal absorption (similar to 89.6% vs. 51.85% for doxorubicin), absence of AMES mutagenicity, and lower predicted acute and chronic oral toxicities in rats. Potential hepatotoxicity and CYP enzyme inhibition were also observed. Molecular docking against EGFR-T790M/V948R revealed that both compound 10 and 11 exhibited a binding affinity of -8.4 and 8.9 kcal/mol, respectively. The interactions of both compounds with key amino acid residues (e.g., LEU 718, VAL 726, ALA 743, MET 790, ASP 855) were consistent with their strong in vitro cytotoxic activity against A549 (EGFR-mutated) cells, supporting their potential as EGFR-targeted anticancer agents.

A novel class of 3-Substituted-5-[(4-oxo-4H-chromen-3-yl)methylene]-2-(2-phenylhydrazineylidene)thiazolidin-4-one (3a-g and 5) was efficiently synthesized via a one-pot three components involving 1-phenyl-4-substituted-thiosemicarbazide, ethyl bromoacetate and 3-formylchromone in absolute ethanol and freshly fused sodium acetate under the effect of ultrasound irradiation at 50 degrees C. The target compounds were obtained in excellent yields within a short time. The synthesized compounds were evaluated for their cytotoxic potential against human breast cancer cell lines MCF-7 and MDA-MB-231 using the sulforhodamine B (SRB) assay. Both compounds 3a and 3f exhibited markedly enhanced cytotoxic activity in comparison to the reference drugs doxorubicin and tamoxifen. These bioactive molecules significantly promoted late-stage apoptosis and necrosis across all tested tumor cell lines. Furthermore, compounds 3a and 3f demonstrated a strong capacity to cause cell-cycle arrest at the G1 and S phases. Additionally, compounds 3a and 3f had potential autophagic induction. ADMET analysis revealed that compound 3a displayed superior oral absorption, a more favorable pharmacokinetic profile, lower toxicity, and no mutagenic risk. Molecular docking studies indicated that both 3a and 3f interact effectively with the VEGFR-2 receptor. These findings suggested that these compounds possess a valuable skeletal structure for the development of novel antitumor agents.

A one-pot, three-component reaction involving 4-oxo-1,4-dihydroquinoline-3-carboxaldehyde (1), acyclic or cyclic active methylene compounds, and diethyl phosphite under mild basic conditions afforded nine novel organophosphorus compounds featuring functionalized 1,2-oxaphosphole heterocycles containing 4-quinolinone ring. The 1,2-azaphospholyl quinolinone and diethyl pyrano[3,2-c]quinolinyl phosphonate derivatives were also obtained. The structures of the synthesized compounds were established on the basis of spectral tools. All synthesized compounds were evaluated for their in vitro cytotoxicity against SKOV-3, MCF-7, and HCT-116 cancer cell lines. Compounds 8a and 8b demonstrated superior selectivity by exhibiting potent cytotoxicity against cancer cells while showing significantly lower toxicity against normal HFB4 cells. Furthermore, these two compounds significantly induced early and late apoptosis as well as reduced cell viability in the studied tumor cells. Additionally, both compounds 8a and 8b exhibited significant potential in halting the cell cycle at various stages, including G1, S, and G2 phases. In the absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, compounds 8a and 8b demonstrated improved oral absorption and genetic safety. Compound 8a showed a more favorable with lower chronic toxicity and minimal metabolic interactions, whereas compound 8b exhibited enhanced intestinal and central nervous system (CNS) permeability. Moreover, both products 8a and 8b were subjected to a molecular docking experiment and displayed good interaction with epidermal growth factor receptor (EGFR). These findings suggested that compounds 8a and 8b possess a valuable skeletal structure for the development of novel antitumor agents.

An innovative and efficient one-pot approach has been established for the synthesis of 3-{1-([5-amino-7-(arylamino)-6-cyano-7H-[1,4]oxaphosphinino[2,3-d]thiazol-2-yl]hydrazinyl)ethylidene}-2H-chromen-2-one (2a-h) using aromatic amine, phosphorus trichloride, malononitrile, and 3-{[1-(4-oxo-5H-thiazol-2-yl)hydrazinyl]ethylidene}-2H-chromen-2-one with triethylamine. This method is efficient and straightforward, offering high yields, easy product isolation, and minimal waste. The cytotoxic properties against PC3, LS174T, and HepG2 cancer cell lines revealed promising activity for compounds 2d and 2e (fluorine and chlorine substitutions), comparable to Tivozanib. Flow cytometry indicated that these bioactive compounds significantly increased late apoptosis and halted cell cycle progression at S and G2 phases, demonstrating their potential as anticancer agents. Both compounds 2d and 2e were then subjected to a molecular docking experiment to see how they bind with VEGFR-2 receptor.

Cu(II), Ni(II), and Co(II) acetates reacted with a thiosemicarbazone ligand (CPPTSC; HL) to produce novel solid complexes with the general formula [M(L)(H2O)m]nH2O, m = 2 or nil, n = 1 or nil, M = Cu(II), Ni(II), and Co(II). Several analytical and spectroscopic techniques have been efficiently used to characterize the synthesized chelates. The investigated CPPTSC ligand functions as a monoanionic tridentate in all chelates. Measurements of molar conductivity showed that all chelates behaved in a non-electrolytic manner. In contrast to nickel-CPPTSC and cobalt-CPPTSC complexes, which showed tetrahedral geometries, the copper-CPPTSC complex showed a distorted octahedral geometry. The thermal decomposition behaviors of CPPTSC complexes were examined using TG. To assess the molecular structural characteristics of CPPTSC and its complexes, density functional theory (DFT) was applied at the B3LYP/6-311G(d,p) and LanL2dz levels. The antiproliferative properties of CPPTSC and its chelates against two human cancer cell lines, HepG-2 (hepatic) and MCF-7 (breast), were evaluated. The Cu-CPPTSC and Ni-CPPTSC complexes displayed the superior IC50 values compared with doxorubicin, suggesting a potentially improved therapeutic index. The bioactive Cu-CPPTSC and Ni-CPPTSC complexes markedly increased the late apoptosis of all studied tumor cells. The Cu-CPPTSC and Ni-CPPTSC complexes showed great cell cycle arrest in the G2 phase and moderate cell cycle arrest in the S phase. The discovered Cu-CPPTSC and Ni-CPPTSC complexes were then subjected to a molecular docking experiment and displayed good interactions with CDK-2 receptor.

A simple synthetic method was performed to design a novel series of polycyclic systems consisting of a coumarin-pyrazole-thiazole skeleton linked with a completed thiazole ring via hydrazone linkage. The methodology depended on the cyclization of the active precursor 2-[(3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazol-4-yl)methylene] hydrazine-1-carbothioamide (2) by its reaction with a series of α-halocarbonyl reagents under Hantzsch reaction conditions. The spectral and analytical data confirmed the structures of all the synthesized compounds. The target compounds were screened for their in vitro anticancer activity. The cytotoxic effects of obtained compound were screened against cancer cell lines (MCF-7, HepG2, and HCT116) using the standard SRB method. Furthermore, products 4, 5, and 7b were the most active against all cancer cell lines, compared with Doxorubicin. These bioactive products effectively suppress the growth of cancer cells by activating the cell death program through late apoptosis. In addition, products 4 and 5 arrested the cell cycle at the S and G2 phases, while product 7b has the ability to arrest the cell cycle at the G2 phase against all three cancer cells. The molecular docking of the products 4, 5, and 7b showed good binding affinities with Cyclin-dependent kinase 8 (CDK-8), while the ADMET prediction supported that these bioactive products can be promising anticancer agents.

Novel derivatives of ethyl 3-substituted-2-{4-oxo-2-(2-((3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazol-4-yl)methylene)hydrazineyl)thiazol-5(4H)-ylidene}acetate (5a-h) were synthesized and assessed for their cytotoxic potential against the liver cancer cell lines Huh-7 and HepG-2. Among these, compounds 5d and 5g demonstrated notable antiproliferative effects, which were benchmarked against the standard drug doxorubicin. To further understand the mechanisms behind their antiproliferative activity, compounds 5d and 5g were investigated for their impact on the cell cycle and their ability to induce apoptosis. They were found to induce significant cellular cycle arrest at the G1 phase. Besides, they potentially enhanced the cellular late apoptosis and reduced the cellular viability. In consent with the apoptosis results, compounds 5d and 5g displayed significant potential autophagic induction against the studied cancer cell lines. Further, both compounds 5d and 5g showed strong interactions with the VEGFR-2 receptor when they were studied using molecular docking. The ADMET prediction indicated that these bioactive compounds have the potential to serve as effective to fight liver cancer.

Recent examples provide clear evidence that ring‐chain tautomerism can be exploited successfully in the synthesis of wide varieties of five‐membered heterocyclic systems. Owing to the versatile chemotherapeutical activities of azoles, the current review mainly focused on employing the ring‐chain tautomeric phenomenon in synthesizing azoles, the five‐membered heterocyclic systems having two hetero‐atoms such as pyrazoles, isoxazoles, oxazoles, imidazoles, thiazoles. Moreover, we discuss the simultaneous existence of ring‐chain tautomerism in two similar or different five‐membered heterocycles, which is known as ring‐ring tautomerism. Also, the three‐, four‐ and five‐component equilibria are reported. In addition, the biological activities of the target azoles are reported.

The need to develop powerful antioxidant agents capable of combating resistant infections without compromising human health has motivated significant research for novel antioxidant compounds. In this study, a series of simple 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol-based Schiff bases were synthesized to investigate their potential as potent antioxidant agents. The methodology involved merging aromatic aldehydes, furan, pyrazole, chromone, and coumarin moieties into a single molecular framework, using Amberlite IR-4B as an acidic catalyst. The structures of compounds 2a-m were confirmed through various spectroscopic techniques and elemental analysis. Additionally, theoretical studies, including in silico computations using the Swiss ADME server, molecular modeling, and Density Functional Theory (DFT) calculations, provided further evidence of the efficiency and stability of the synthesized compounds. Among the series, compound 2b exhibited the most prominent antioxidant activity (2.25 +/- 0.18 mu g/mL), outperforming the standard. Moreover, molecular docking studies revealed that the investigated bioactive compounds occupy the same binding cavity as the well-known antioxidant ascorbic acid (ASC).

A series of novel chromone derivatives bearing a thiosemicarbazone moiety (3a-i and 5) at the C-3 position was efficiently synthesized using ultrasound irradiation. The compounds were evaluated for in vitro cytotoxicity against T24 (bladder transitional cell carcinoma) and PC3 (human prostate adenocarcinoma) cell lines. Compounds 3b (R ═ Me) and 3g (R ═ benzyl) exhibited the most potent cytotoxicity, outperforming doxorubicin. These two compounds significantly induced late apoptosis and necrosis, arrested the cell cycle at distinct phases in both cell lines, and demonstrated potential for autophagic induction. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions for them indicated favorable drug-like properties for these compounds, supporting their potential as anticancer agents. Molecular docking studies for both 3b and 3g revealed strong interactions with VEGFR-2 receptor, further highlighting their promise as scaffolds for novel antitumor drug development.

A novel series of ethyl {3-substituted-4-oxo-2-[(4-oxo-4H-chromen-3-yl)methylene] hydrazineylidene}thiazolidin-5-ylidene}acetate derivatives (3a-h) was efficiently synthesized via a one-pot, three-component reaction helped by ultrasonic irradiation. These newly eight compounds were assessed for their cytotoxic effects against SKOV-3 and HeLa cancer cell lines. Among them, both compounds 3c and 3e demonstrated the most potent antiproliferative activities in the comparison with doxorubicin. To elucidate their biological mechanisms, cell cycle analysis and apoptosis assays were performed. Both compounds 3c and 3e significantly reduced cell viability and promoted apoptosis in the tested cell lines. Moreover, these compounds effectively caused cell cycle arrest at the S and G2 phases in SKOV-3 cells and at the G1 phase in HeLa cells. Supporting these findings, both compounds also triggered substantial autophagic responses. In silico ADMET study revealed that both 3c and 3e surpassed doxorubicin in terms of intestinal absorption, central nervous system (CNS) permeability and genomic safety. Particularly, compound 3e may exhibit excellent oral bioavailability, lower predicted toxicity, and an improved safety profile. Additionally, molecular docking studies indicated strong binding interactions between both compounds and the VEGFR-2 receptor, highlighting their potential as promising scaffolds for future anticancer drug development.

A green and efficient ultrasound-mediated protocol was developed for the synthesis of a series of novel Schiff bases derived from quinoline-4-one. The synthetic strategy involved the condensation of 4-oxo-1,4-dihydro-quinoline-3-carboxaldehyde with diverse anilines and heteroaryl amines. The synthesized compounds were characterized using spectroscopic techniques. A comprehensive in vitro cytotoxicity evaluation against HCT116 and HT-29 human colon cancer cell lines revealed that several compounds exhibited potent anticancer activity. Notably, compounds 3c and 3e demonstrated superior cytotoxicity compared to the clinical standard doxorubicin. Mechanistic studies indicated that these lead compounds induced apoptosis, necrosis, and cell cycle arrest at G1 and G2 phases. Furthermore, autophagy induction was observed. In silico ADMET predictions support the potential of compounds 3c and 3e as promising anticancer drug candidates. The molecular docking studies revealed that the Schiff bases 3c and 3e displayed good interaction with VEGFR-2 receptor. These findings underscore the quinoline-4-one scaffold as a valuable template for the development of novel antitumor agents.

A novel series of coumarin-pyrazole-thiazoles hybrids was designed. The methodology depended on a simple condensation reaction of 3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carboxaldehyde with a variety of thiazole compounds having amino or active methylene groups. In addition, another series of 1-(thiazol-2-yl)-3-(2-oxo-2H-chromen-3-yl)-1H-pyrazole-4-carboxaldehydes was also achieved by applying Vilsmeier-Haack formylation on 3-[1-(2-(thiazol-2-yl)hydrazineylidene]ethyl)-2H-chromen-2-ones. The obtained products were verified by spectral techniques such as IR, NMR, and mass spectra. To screen their abilities to inhibit cancer cell growth, these compounds were investigated against three tumor cell lines (MCF-7, HepG2, and HCT116) using a standard method called SRB. The products 3 e, 7 b, 12 c and 14 a have considerable cytotoxic effects comparable to Doxorubicin. These products caused significant cell death by late apoptosis in all tumor cell lines. Furthermore, they preferentially induced G2 cell cycle arrest in MCF-7 and HepG2 cells, while causing G1 cell cycle arrest in HCT116 cells. The molecular docking of these bioactive products showed good binding affinities with Cyclin-dependent kinase 8 (CDK-8). The ADMET-predicted drug-likeness properties of these bioactive compounds enable them to can used as promising anticancer agents.

With the ultimate goal of discovering new anticancer agents, this study involved the design and synthesis of fifteen novel Schiff bases 4a,b, 5, 6a–d, 7a–e, and 8–10 which contain 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole moiety. The synthetic method depended on reaction of 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (3) with a series of aromatic and heteroaryl amines under ultrasound irradiation to explore the influence of aromatic and heteroaryl rings on biological activity. The chemical structures of these Schiff bases were fully elucidated using various spectral and elemental analyses. The antiproliferative activities of the Schiff bases were studied by the standard SRB method. Among the new 15 Schiff bases, derivatives 4a,b, 5, and 7b have significant cytotoxic effects against PC3, HepG2, and HCT116 cancer cell lines. These four bioactive Schiff bases significantly increased the late apoptosis of all studied tumor cells. Also, both products 4a and 4b arrested the cell cycle at the G1 phase, while both compounds 5 and 7b arrested the S and G2 phases against PC3 cells. In addition, the products 4a, 4b, 5, and 7b have promising high abilities to arrest the cell cycle at the G2 phase against HepG2 and HCT116 cells. The different substitutions on the aryl ring were the basis for the structure–activity relationship study. The molecular docking study confirmed good binding interactions of these compounds with Cyclin-dependent kinase 8 (CDK-8) receptor, while the absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction supported that these bioactive products can be promising anticancer agents.

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. [Graphics]

A novel series of 4-[3-acetyl-2-(N-alkyl(aryl)acetamido)-1,3,4-thiadiazol-5-yl]-3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazoles (2a-i) and 3 was synthesized in good yields. The methodology was depended on a one-pot four-components reaction of hydrazine hydrate, alkyl(aryl) isothiocyanate, 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (1), and acetic anhydride in acetic acid under ultrasound irradiation. The spectral tools confirmed the structures of all synthesized compounds. Using the standard SRB method, the designed compounds were screened for their in vitro cytotoxicity properties against PC3, HepG2, and HCT116 human cancer cell lines. Products 2a and 2c worked best against all cancer cells tested, as well as doxorubicin. Apoptosis and cell cycle analyses were performed for the bioactive products 2a and 2c. Both products strongly impacted all tumor cells in the late apoptotic pathway and significantly inhibited all cancer cell types under investigation in both the S and G2 phases. After that, a molecular docking study was carried out on products 2a and 2c to investigate how they interact with the CDK-8 receptor. The ADMET prediction suggested that these bioactive products may be effective anticancer treatments.