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Molecular Diversity Apr 2022For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts...
For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by H NMR, C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography. In vitro screening of the antimicrobial activity of all compounds (3a-t) was evaluated against five bacterial and two fungal strains. This study disclosed that N-{[(3-chlorophenyl)]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)}piperazine-1-carboxamide (3o) was the superior antimicrobial with good growth inhibition against A. baumannii. Furthermore, the results from the performed molecular docking studies were promising, since the observed data could be used to develop more potent antimicrobials.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Piperazine; Pyrazines; Structure-Activity Relationship
PubMed: 33547619
DOI: 10.1007/s11030-021-10190-x -
Molecular Pharmaceutics Sep 2017In the present study, a new coamorphous phase (CAP) of bioactive herbal ingredient curcumin (CUR) with high solubilitythe was screened with pharmaceutically acceptable...
Preparation of Curcumin-Piperazine Coamorphous Phase and Fluorescence Spectroscopic and Density Functional Theory Simulation Studies on the Interaction with Bovine Serum Albumin.
In the present study, a new coamorphous phase (CAP) of bioactive herbal ingredient curcumin (CUR) with high solubilitythe was screened with pharmaceutically acceptable coformers. Besides, to provide basic information for the best practice of physiological and pharmaceutical preparations of CUR-based CAP, the interaction between CUR-based CAP and bovine serum albumin (BSA) was studied at the molecular level in this paper. CAP of CUR and piperazine with molar ratio of 1:2 was prepared by EtOH-assisted grinding. The as-prepared CAP was characterized by powder X-ray diffraction, modulated temperature differential scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared, and solid-state C nuclear magnetic resonance. The 1:2 CAP stoichioimetry was sustained by C═O···H hydrogen bonds between the N-H group of the piperazine and the C═O group of CUR; piperazine stabilized the diketo structure of CUR in CAP. The dissolution rate of CUR-piperazine CAP in 30% ethanol-water was faster than that of CUR; the t values were 243.1 min for CUR and 4.378 min for CAP. Furthermore, interactions of CUR and CUR-piperazine CAP with BSA were investigated by fluorescence spectroscopy and density functional theory (DFT) calculation. The binding constants (K) of CUR and CUR-piperazine CAP with BSA were 10.0 and 9.1 × 10 L mol at 298 K, respectively. Moreover, DFT simulation indicated that the interaction energy values of hydrogen-bonded interaction in the tryptophan-CUR and tryptophan-CUR-piperazine complex were -26.1 and -17.9 kJ mol, respectively. In a conclusion, after formation of CUR-piperazine CAP, the interaction forces between CUR and BSA became weaker.
Topics: Animals; Cattle; Curcumin; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Piperazine; Piperazines; Serum Albumin, Bovine; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 28703594
DOI: 10.1021/acs.molpharmaceut.7b00217 -
Metallomics : Integrated Biometal... Oct 2022Three ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes Ru1-Ru3 were designed and synthesized for evaluating antitumor activity. All the...
Three ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes Ru1-Ru3 were designed and synthesized for evaluating antitumor activity. All the complexes exhibited high in vitro cytotoxicity against MGC-803, T24, HepG2, CNE2, MDA-MB-231, MCF-7, A549, and A549/DDP cell lines. Ru1, Ru2, and Ru3 were 11, 8 and 10 times, respectively, more active than cisplatin against A549/DDP. An in vivo study on MGC-803 xenograft mouse models demonstrated that representative Ru2 exhibited an effective inhibitory effect on tumor growth, showing stronger antitumor activity than cisplatin. Biological investigations suggested that Ru2 entered MGC-803 cells by a clathrin-mediated endocytic pathway, initially localizing in the lysosomes and subsequently escaping and localizing in the mitochondria. Mitochondrial swelling resulted in vacuolization, which induced vacuolation-associated cell death and necroptosis with the formation of necrosomes (RIP1-RIP3) and the uptake of propidium iodide. These results demonstrate that the potential of Ru2 as a chemotherapeutic agent to kill cancer cells via a dual mechanism represents an alternative way to eradicate apoptosis-resistant forms of cancer.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cisplatin; Clathrin; Coordination Complexes; Humans; Mice; Necroptosis; Oleanolic Acid; Piperazine; Propidium; Ruthenium; Ursolic Acid
PubMed: 36149330
DOI: 10.1093/mtomcs/mfac072 -
European Journal of Medicinal Chemistry Nov 2022Microglia-mediated neuroinflammation plays an important role in ischemic stroke (IS). In this work, a series of novel indole and indazole-piperazine pyrimidine...
Microglia-mediated neuroinflammation plays an important role in ischemic stroke (IS). In this work, a series of novel indole and indazole-piperazine pyrimidine derivatives with anti-neuroinflammatory and neuroprotective activities were designed and synthesized for treatment of IS. Among these compounds, 5j displayed the most attractive cytoprotective effect against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced damage in BV2 cells. Meanwhile, it significantly ameliorated the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2), from lipopolysaccharide (LPS)-induced BV2 cells. Moreover, 5j can decrease the release of TNF-α and IL-1β form LPS-induced mouse brain neuroinflammation model. As a potent inhibitor against both cyclooxygenase-2 (COX-2, IC = 92.54 nM) and 5-lipoxygenase (5-LOX, IC = 41.86 nM), 5j inhibited the M1 phenotype polarization of microglia and promoted the M2 phenotype polarization of microglia. Additionally, 5j exhibited remarkable neuroprotection in middle cerebral artery occlusion (MCAO) rats by reducing their infarct volumes and neurological deficit scores. In conclusion, 5j has the potential for the treatment of stroke as an anti-inflammatory and neuroprotective agent.
Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Cyclooxygenase 2; Disease Models, Animal; Indazoles; Indoles; Ischemic Stroke; Lipopolysaccharides; Mice; Microglia; Neuroprotection; Neuroprotective Agents; Piperazine; Pyrimidines; Rats; Stroke; Tumor Necrosis Factor-alpha
PubMed: 35931005
DOI: 10.1016/j.ejmech.2022.114597 -
Molecules (Basel, Switzerland) Jul 2022Piperazine-based dithiocarbamates serve as important scaffolds for numerous pharmacologically active drugs. The current study investigates the design and synthesis of a...
Ultrasound-Assisted Synthesis and In Silico Modeling of Methanesulfonyl-Piperazine-Based Dithiocarbamates as Potential Anticancer, Thrombolytic, and Hemolytic Structural Motifs.
Piperazine-based dithiocarbamates serve as important scaffolds for numerous pharmacologically active drugs. The current study investigates the design and synthesis of a series of dithiocarbamates with a piperazine unit as well as their biological activities. Under ultrasound conditions, the corresponding piperazine-1-carbodithioates were synthesized from monosubstituted piperazine and -phenylacetamides in the presence of sodium acetate and carbon disulfide in methanol. The structures of the newly synthesized piperazines were confirmed, and their anti-lung carcinoma effects were evaluated. A cytotoxic assay was performed to assess the hemolytic and thrombolytic potential of the synthesized piperazines . The types of substituents on the aryl ring were found to affect the anticancer activity of piperazines . Piperazines containing 2-chlorophenyl (; cell viability = 25.11 ± 2.49) and 2,4-dimethylphenyl (; cell viability = 25.31 ± 3.62) moieties demonstrated the most potent antiproliferative activity. On the other hand, piperazines containing 3,4-dichlorophenyl (; 0.1%) and 3,4-dimethylphenyl (; 0.1%) rings demonstrated the least cytotoxicity. The piperazine with the 2,5-dimethoxyphenyl moiety (; 60.2%) showed the best thrombolytic effect. To determine the mode of binding, in silico modeling of the most potent piperazine (i.e., ) was performed, and the results were in accordance with those of antiproliferation. It exhibits a similar binding affinity to PQ10 and an efficient conformational alignment with the lipophilic site of PDE10A conserved for PQ10A.
Topics: Antineoplastic Agents; Cell Survival; Computer Simulation; Piperazine; Piperazines; Structure-Activity Relationship
PubMed: 35897953
DOI: 10.3390/molecules27154776 -
Mini Reviews in Medicinal Chemistry 2018The serotonin system exerts its effects on the CNS and many peripheral systems. Of the 14 serotonin receptors, the 5-HT7 receptor is the most recently discovered. The... (Comparative Study)
Comparative Study Review
The serotonin system exerts its effects on the CNS and many peripheral systems. Of the 14 serotonin receptors, the 5-HT7 receptor is the most recently discovered. The 5-HT7 receptor has been shown to be involved in stress reduction, depression, and nociceptive control. Despite the 20 years since the discovery of 5-HT7R, there are still few truly selective ligands. Two of the common scaffolds for 5-HT7R ligands are long chain arylpiperazines (LCAPs) and sulfonamide containing compounds. This review focuses on recently developed (2014-2016) 5-HT7R ligands, their selectivity for the receptor, and suggests the possible new pharmacophore models for these ligands.
Topics: Drug Discovery; Humans; Ligands; Molecular Structure; Piperazine; Piperazines; Receptors, Serotonin; Structure-Activity Relationship; Sulfonamides
PubMed: 28901854
DOI: 10.2174/1389557517666170913111533 -
Journal of Pharmaceutical and... Aug 2024Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the...
Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MS spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds' antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.
Topics: Morpholines; Anti-Bacterial Agents; Microbial Sensitivity Tests; Piperazines; Gram-Negative Bacteria; Mass Spectrometry; Gram-Positive Bacteria; Structure-Activity Relationship; Piperazine
PubMed: 38820833
DOI: 10.1016/j.jpba.2024.116202 -
European Journal of Medicinal Chemistry Mar 2015Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB...
Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast cancer, MIA PaCa2 pancreatic cancer, and NCI H1975 non-small cell lung cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 μΜ, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts).
Topics: Adamantane; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Design; HeLa Cells; Humans; Piperazine; Piperazines; Receptors, sigma
PubMed: 25703296
DOI: 10.1016/j.ejmech.2015.02.021 -
Journal of the American Chemical Society Nov 2022Artificial photosynthesis of HO from O reduction provides an energy-saving, safe, and green approach. However, it is still critical to develop highly active and...
Artificial photosynthesis of HO from O reduction provides an energy-saving, safe, and green approach. However, it is still critical to develop highly active and selective 2e oxygen reduction reaction photocatalysts for efficient HO production owing to the unsatisfactory photosynthesis productivity. Herein, two new two-dimensional piperazine-linked CoPc-based covalent organic frameworks (COFs), namely, CoPc-BTM-COF and CoPc-DAB-COF, were afforded from the nucleophilic substitution reaction of hexadecafluorophthalocyaninato cobalt(II) (CoPcF) with 1,2,4,5-benzenetetramine (BTM) or 3,3'-diaminobenzidine (DAB). Powder X-ray diffraction analysis in combination with electron microscopy and a series of spectroscopic technologies reveals their crystalline porous framework with a fully conjugated structure and eclipsed π-stacking model. Ultraviolet-visible diffuse reflectance absorption spectra unveil their excellent light absorption capacity in a wide range of 400-1000 nm. This, together with their enhanced photo-induced charge separation and transport efficiency as disclosed by photocurrent response and photoluminescence measurements, endows the as-prepared piperazine-linked CoPc-based COFs with superior photocatalytic activity toward O-to-HO conversion under visible-light irradiation (λ > 400 nm). In particular, CoPc-BTM-COF exhibits a record-high HO yield of 2096 μmol h g among the COF-based photocatalysts and an impressive apparent quantum yield of 7.2% at 630 nm. The present result should be helpful for fabricating high-performance and low-cost photocatalysts for visible-light-driven HO photosynthesis.
Topics: Hydrogen Peroxide; Piperazine; Light; Photosynthesis
PubMed: 36350764
DOI: 10.1021/jacs.2c09482 -
International Journal of Molecular... Jun 2023In this paper, a series of derivatives were synthesized by introducing the pharmacophore pyrazole ring and piperazine ring into the structure of the natural product...
In this paper, a series of derivatives were synthesized by introducing the pharmacophore pyrazole ring and piperazine ring into the structure of the natural product myricetin through an amide bond. The structures were determined using carbon spectrum and hydrogen spectrum high-resolution mass spectrometry. Biological activities of those compounds against bacteria, including (), () and () were tested. Notably, exhibited significant bioactivity against with an EC value of 18.8 μg/mL, which was higher than the control drugs thiadiazole-copper (EC = 52.9 μg/mL) and bismerthiazol (EC = 69.1 μg/mL). Furthermore, the target compounds were assessed for their antifungal activity against ten plant pathogenic fungi. Among them, displayed excellent inhibitory activity against sp. with an EC value of 16.9 μg/mL, outperforming the control agents azoxystrobin (EC = 50.7 μg/mL) and fluopyram (EC = 71.8 μg/mL). In vitro tests demonstrated that possessed curative (60.6%) and protective (74.9%) effects on postharvest kiwifruit. To investigate the active mechanism of , its impact on SDH activity was evaluated based on its structural features and further confirmed through molecular docking. Subsequently, the malondialdehyde content of -treated fungi was measured, revealing that could increase malondialdehyde levels, thereby causing damage to the cell membrane. Additionally, the EC value of on was 11.3 μg/mL, which was superior to the control drug azoxystrobin (EC = 35.1 μg/mL), and the scanning electron microscopy results indicated that the surface of drug-treated mycelium was ruffled, and growth was significantly affected.
Topics: Amides; Piperazine; Molecular Docking Simulation; Anti-Bacterial Agents; Microbial Sensitivity Tests; Xanthomonas; Plant Diseases; Oryza; Structure-Activity Relationship
PubMed: 37445627
DOI: 10.3390/ijms241310442