Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition.

In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.

An Overview of Pyridazinone Analogs: Chemical and Pharmacological Potential.

Pyridazinones are classical molecules that occupy an important place in heterocyclic chemistry, and since their discovery, they have been widely developed. The introduction of new functional groups into pyridazinone structures has enabled the synthesis of a large diversity of compounds. The pharmacological and agrochemical importance of pyridazinone derivatives has aroused the interest of chemists and directed their research toward the synthesis of new compounds with the aim of improving their biological effectiveness. In this review, we have compiled and discussed the different synthetic routes, reactivity, and pharmacological and agrochemical applications of the pyridazinone ring.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model.

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%-50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents.

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.

Chalcone-based imidazo[2,1-b]thiazole derivatives: synthesis, crystal structure, potent anticancer activity, and computational studies.

In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔGBind), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard.Communicated by Ramaswamy H. Sarma.

Novel Pyrazole-Based Benzofuran Derivatives as Anticancer Agents: Synthesis, Biological Evaluation, and Molecular Docking Investigations.

In this work, the design, synthesis, and mechanistic studies of novel pyrazole-based benzofuran derivatives 1-8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A-549, human-derived colorectal adenocarcinoma HT-29, breast adenocarcinoma MCF-7 cells as well as mouse fibroblast 3T3-L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose-dependent anti-proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti-proliferative activity with an IC50 value of 7.31 µM and the highest selectivity (15.74) on MCF-7 cells. Flow cytometry results confirmed that the cytotoxic power of compound 2 on MCF-7 cells is closely related to mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase-3 via in-silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.

CuII Pyrazolyl-Benzimidazole Dinuclear Complexes with Remarkable Antioxidant Activity.

Three dinuclear coordination complexes generated from 1-n-butyl-2-((5-methyl-1H-pyrazole-3-yl)methyl)-1H-benzimidazole (L), have been synthesized and characterized spectroscopically and structurally by single crystal X-ray diffraction analysis. Reaction with iron(II) chloride and then copper(II) nitrate led to a co-crystal containing 78 % of [Cu(NO3 )(µ-Cl)(L')]2 (C1 ) and 22 % of [Cu(NO3 )(µ-NO3 )(L')]2 (C2 ), where L was oxidized to a new ligand L' . A mechanism is provided. Reaction with copper chloride led to the dinuclear complex [Cu(Cl)(µ-Cl)(L)]2 (C3 ). The presence of N-H⋅⋅⋅O and C-H⋅⋅⋅O intermolecular interactions in the crystal structure of C1 and C2 , and C-H⋅⋅⋅N and C-H⋅⋅⋅Cl hydrogen bonding in the crystal structure of C3 led to supramolecular structures that were confirmed by Hirshfeld surface analysis. The ligands and their complexes were tested for free radical scavenging activity and ferric reducing antioxidant power. The complex C1 /C2 shows remarkable antioxidant activities as compared to the ligand L and reference compounds.

Validation of an HPLC Method for the Determination of Diclofenac Diethylamine and Three of Its Impurities in a Gel Pharmaceutical Form.

BACKGROUND: Monitoring impurities in drug products is a principal requirement of pharmaceutical regulatory authorities all over the world to ensure drug safety. For this reason, there is a great need for analytical QC of dugs products. OBJECTIVE: In this study, a simple, efficient, and direct HPLC method was developed for the determination of three impurities of diclofenac. METHODS: The HPLC method was developed using a mobile phase which consisted of an HPLC grade mixture, acetonitrile-0.01M phosphoric acid adjusted to pH 2.3 (1 + 3, by volume). RESULTS: The separation was performed in 15 min. The calibration curves of the three impurities were linear; the correlation coefficients were 0.999 at concentrations of 0.00015-0.003 µg/mL. CONCLUSION: The validation of this method shows that it meets all validation criteria. This shows the reliability of this method for the routine control of diclofenac impurities. HIGHLIGHTS: The validation of a robust HPLC method for the determination of diclofenac impurities is of great importance for the pharmaceutical industry to control its products.

Green synthesis, characterization, and biochemical impacts of new bioactive isoxazoline-sulfonamides as potential insecticidal agents against the Sphodroxia maroccana Ley.

BACKGROUND: Sphodroxia maroccana Ley is a pest of cork oak crops that damages the roots of seedlings and can severely impair cork oak regeneration. Since the banning of carbosulfan and chlorpyriphos, which were widely used against the larvae of Sphodroxia maroccana because of their harmful impact on the environment, until now there has been no pesticide against these pests. Therefore, it is particularly urgent to develop highly effective insecticidal molecules with novel scaffolds. Isoxazolines are a class of insecticides that act on γ-aminobutyric acid (GABA)-gated chloride channel allosteric modulators. In this work, a green synthesis of novel 3,5-disubstituted isoxazoline-sulfonamide derivatives was achieved in water via ultrasound-assisted four-component reactions, and their insecticidal activities against fourth-instar larvae of S. maroccana were evaluated. RESULTS: Most of the tested compounds showed insecticidal activity compared to fluralaner as positive control and commercially available insecticide. Especially, the isoxazoline-secondary sulfonamides containing halogens (Br and Cl) on the phenyl group attached to the isoxazoline, 6g (LC50 = 0.31 mg/mL), 6j (LC50 = 0.38 mg/mL), 6k (LC50 = 0.18 mg/mL), 6L (LC50 = 0.49 mg/mL), 6m (LC50 = 0.24 mg/mL), 6q (LC50 = 0.46 mg/mL), exhibited much higher larvicidal activity than fluralaner (LC50 = 0.99 mg/mL). CONCLUSION: Novel isoxazolines containing sulfonamide moieties were designed, synthesized and confirmed by two single-crystal structures of 4e and 6q. Their bioassay results showed significant larvicidal activity with significant morphological changes in vivo. These results will lay the foundation for the further discovery and development of isoxazoline-sulfonamide derivatives as novel crop protection larvicides of cork oak. © 2023 Society of Chemical Industry.

Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives.

In this work, a novel series of pyridazinone derivatives (3-17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74-8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy framework, docking and molecular dynamic simulations of (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one as anticancer agent.

In this work, a novel crystal, (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (E-BSP) was synthesized via Knoevenagel condensation of benzaldehyde and (E)-6-(4-methoxystyryl)-4,5-dihydropyridazin-3(2H)-one. The molecular structure of E-BSP was confirmed by using FT-IR, 1H-NMR, 13C-NMR, UV-vis, ESI-MS, TGA/DTA thermal analyses and single crystal X-ray diffraction. The DFT/B3LYP methods with the 6-311++G(d,p) basis set were used to determine the vibrational modes over the optimized structure. Potential energy distribution (PED) and the VEDA 4 software were used to establish the theoretical mode assignments. The same approach was used to compute the energies of frontier molecular orbitals (HOMO-LUMO), global reactivity descriptors, and molecular electrostatic potential (MEP). Additionally, experimental and computed UV spectral parameters were determined in methanol and the obtained outputs were supported by FMO analysis. Molecular docking and molecular dynamics (MD) simulation analyses of the E-BSP against six proteins obtained from different cancer pathways were carried out. The proteins include; epidermal growth factor receptor (EGFR), Estrogen receptor (ERα), Mammalian target of rapamycin (mTOR), Progesterone receptor (PR) (Breast cancer), Human cyclin-dependent kinase 2 (CDK2) (Colorectal cancer), and Survivin (Squamous cell carcinoma/Non-small cell lung cancer). The results of the analyses showed that the compound had less binding energies ranging between -6.30 to -9.09 kcal/mol and formed stable complexes at the substrate-binding site of the proteins after the 50 ns MD simulation. Therefore, E-BSP was considered a potential inhibitor of different cancer pathways and should be used for the treatment of cancer after experimental validation and clinical trial.Communicated by Ramaswamy H. Sarma.

Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents.

In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 µM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.

Targeting EGFR, RSK1, RAF1, PARP2 and LIN28B for several cancer type therapies with newly synthesized pyrazole derivatives via a computational study.

Cancer remains the leading cause of death in the world despite the significant advancements made in anticancer drug discovery. This study is aimed to computationally evaluate the efficacy of 63 in-house synthesized pyrazole derivatives targeted to bind with prominent cancer targets namely EGFR, RSK1, RAF1, PARP2 and LIN28B known to be expressed, respectively, in lung, colon, skin, ovarian and pancreatic cancer cells. Initially, we perform the molecular docking investigations for all pyrazole compounds with a comparison to known standard drugs for each target. Docking studies have revealed that some pyrazole compounds possess better binding affinity scores than standard drug compounds. Thereafter, a long-range of 1 µs molecular dynamic (MD) simulation study for top ranked docked compounds with all respective proteins was carried out to assess the interaction stability in a dynamic environment. The results suggested that the top ranked complexes showed a stable interaction profile for a longer period of time. The outcome of this study suggests that pyrazole compounds, M33, M36, M76 and M77, are promising molecular candidates that can modulate the studied target proteins significantly in comparison to their known inhibitor based on their selective binding interactions profile. Furthermore, ADME-T profile has been explored to check for the drug-likeness and pharmacokinetics profiles and found that all proposed compounds exhibited acceptable values for being a potential drug-like candidate with non-toxic characteristics. Overall, extensive computational investigations indicate that the four proposed pyrazole inhibitors/modulators studied against each respective target protein will be helpful for future cancer therapeutic developments.Communicated by Ramaswamy H. Sarma.

A Preliminary Study on the Potential of FT-IR Spectroscopy and Chemometrics for Tracing the Geographical Origin of Moroccan Virgin Olive Oils.

BACKGROUND: The authentication of the geographical origin of virgin olive oils (VOO) generally requires the use of sophisticated and time-consuming analytical techniques. There is a need for quick and simple analytical techniques to predict the origin of olive oils. OBJECTIVE: This study aims to examine the physico-chemical data of olive oils collected in six regions of Morocco during two consecutive years 2020 and 2021, and also to evaluate the ability of FT-IR in combination with discrimination tools to study the geographical origin of Moroccan olive oils. METHOD: Fourier transform infrared spectroscopy (FTIR) was used in this study as an emerging analytical technique to express a unique "fingerprint." A preliminary processing of the ATR-FTIR spectral data was performed by preprocessing algorithm to reduce the noise and the effect of signal variation as well as to minimize the effects of light scattering to extract the maximum analytical information from the spectra. A multivariate statistical procedure based on principal component analysis (PCA) coupled with linear discriminant analysis (LDA) as well as partial least-squares discriminant analysis (PLS-DA) was developed to provide a powerful classification approach. RESULTS: Based on the PCA, six clusters were identified. The application of PCA-LDA and PLS-DA procedures demonstrate a powerful capacity in predicting the geographic origin of olive oils; this capacity is shown by the high value of correct classification rate (CCR), varying between 84.09 and 100%. CONCLUSIONS: The suggested procedure has given reliable results for the classification of olive oils according to their geographical origin, with advantages such as being fast, inexpensive, and not requiring any prior separation process. HIGHLIGHTS: The performance of this approach is significantly faster and possesses a higher degree of selectivity and sensitivity. The implementation of this technique for routine analysis of olive oil would save significant time, resources, and solvents.

In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC-Application towards Cancer Therapeutics.

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein-ligand contact maps were derived from trajectories of simulated protein-ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein-ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.

Design and prediction of novel pyrazole derivatives as potential anti-cancer compounds based on 2D-2D-QSAR study against PC-3, B16F10, K562, MDA-MB-231, A2780, ACHN and NUGC cancer cell lines.

Despite the decades of scientific studies for developing promising new therapies, cancer remains a major cause of illness and mortality, worldwide. Several cancer types are the major topic of research in drug discovery programs due to their global incidence cases and growing frequency. In the present study, using two different statistical approaches PCA (principal component analysis) and PLS (partial least squares), six 2D-QSAR (quantitative structure activity relationship) models have been developed for the set of compounds retrieved against seven cancer cell lines vizPC-3, B16F10, K562, MDA-MB-231, A2780, and ACHN. For the creation and validation of 2D-QSAR models, OECD (Organization for Economic Co-operation and Development) requirements have been strictly followed. All of the generated 2D-QSAR models produce a significant and high correlation coefficient value with several other statistical parameters. Moreover, developed 2D-QSAR models have been used for activity predictions of in-house synthesized 63 pyrazole derivatives compounds. Precisely, most statistically significant and accepted2D-QSAR model generated for each cancer cell line has been used to predict the pIC50 value (anti-cancer activity) of all 63 synthesized pyrazole derivatives. Furthermore, designing of novel pyrazole derivatives has been carried out by substituting the essential functional groups based on the best derived 2D-QSAR models for each cancer cell line, more precisely, based on the most significant molecular descriptors with enhanced anti-cancer activity. Finally, the prediction of the new designed molecules reveals higher pIC50 than the standard compounds.

Crystal structure of (E)-3-({6-[2-(4-chloro-phen-yl)ethen-yl]-3-oxo-2,3-di-hydro-pyridazin-4-yl}meth-yl)pyridin-1-ium chloride dihydrate.

In the title compound, C18H15ClN3O+·Cl-·2H2O, three intra-mol-ecular hydrogen bonds are observed, N-H⋯O, O-H⋯Cl and O-H⋯O. In the crystal, mol-ecules are connected by C-H⋯Cl and N-H⋯O hydrogen bonds. Strong C-H⋯Cl, N-H⋯O, O-H⋯Cl and O-H⋯O hydrogen-bonding inter-actions are implied by the Hirshfeld surface analysis, which indicate that H⋯H contacts make the largest contribution to the overall crystal packing at 33.0%.

Crystal structure and Hirshfeld surface analysis of 2-oxo-2-phenyl-ethyl 3-nitroso-2-phenyl-imidazo[1,2-a]pyridine-8-carboxyl-ate.

The title compound, C22H15N3O4, is built up from a central imidazo[1,2-a]pyridine ring system connected to a nitroso group, a phenyl ring and a 2-oxo-2-phenyl-ethyl acetate group. The imidazo[1,2-a] pyridine ring system is almost planar (r.m.s. deviation = 0.017 Å) and forms dihedral angles of 22.74 (5) and 45.37 (5)°, respectively, with the phenyl ring and the 2-oxo-2-phenyl-ethyl acetate group. In the crystal, the mol-ecules are linked into chains parallel to the b axis by C-H⋯O hydrogen bonds, generating R 2 1 (5) and R 4 4 (28) graph-set motifs. The chains are further linked into a three-dimensional network by C-H⋯π and π-stacking inter-actions. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from H⋯H (36.2%), H⋯C/C⋯H (20.5%), H⋯O/O⋯H (20.0%), C⋯O/O⋯C (6.5%), C⋯N/N⋯C (6.2%), H⋯N/N⋯H (4.5%) and C⋯C (4.3%) inter-actions.

Coordination complexes constructed from pyrazole-acetamide and pyrazole-quinoxaline: effect of hydrogen bonding on the self-assembly process and antibacterial activity.

Two mononuclear coordination complexes of N-(2-aminophenyl)-2-(5-methyl-1H-pyrazol-3-yl)acetamide (L1), namely [Cd(L1)2Cl2] (C1) and [Cu(L1)2(C2H5OH)2](NO3)2 (C2) and one mononuclear complex [Fe(L2)2(H2O)2](NO3)2·2H2O (C3), obtained after in situ oxidation of L1, have been synthesized and characterized spectroscopically. As revealed by single-crystal X-ray diffraction, each coordination sphere made of two heterocycles is completed either by two chloride anions (in C1), two ethanol molecules (in C2) or two water molecules (in C3). The crystal packing analysis of C1, C2 and C3, revealed 1D and 2D supramolecular architectures, respectively, via various hydrogen bonding interactions, which are discussed in detail. Furthermore, evaluation in vitro of the ligands and their metal complexes for their antibacterial activity against Escherichia coli (ATCC 4157), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923) and Streptococcus fasciens (ATCC 29212) strains of bacteria, revealed outstanding results compared to chloramphenicol, a well-known antibiotic, with a normalized minimum inhibitory concentration as low as 5 µg mL-1.

Crystal structure and Hirshfeld surface analysis of 6-((E)-2-{4-[2-(4-chloro-phen-yl)-2-oxoeth-oxy]phen-yl}ethen-yl)-4,5-di-hydro-pyridazin-3(2H)-one.

The pyridazine ring in the title compound, C20H17ClN2O3, adopts a screw-boat conformation. The whole mol-ecule is flattened, the dihedral angles subtended by the least-squares plane of the central aromatic ring with those of the terminal benzene and pyridazine rings being 15.18 (19) and 11.23 (19)°, respectively. In the crystal, the mol-ecules are linked by pairs of N-H⋯O bonds into centrosymmetric dimers and by C-H⋯π contacts into columns. The results of the Hirshfeld surface analysis show that the most prominent inter-actions are H⋯H, accounting for 36.5% of overall crystal packing, and H⋯O/O⋯H (18.6% contribution) contacts.