24721-24-2Relevant articles and documents
Synthesis, characterization and α-amylase and α-glucosidase inhibition studies of novel vanadyl chalcone complexes
Kaur, Mandeep,Kaushal, Raj
, (2021)
A series of chalcone ligands and their corresponding vanadyl complexes of composition [VO (LI–IV)2(H2O)2]SO4 (where LI = 1,3-Diphenylprop-2-en-1-one, LII = 3-(2-Hydroxy-phenyl)-1-phenyl-propenone, LIII = 3-(3-Nitro-phenyl)-1-phenyl-propenone, LIV = 3-(4-Methoxy-phenyl)-1-phenyl-propenone) have been synthesized and characterized using various spectroscopic (Fourier-transform infrared, electrospray ionization mass, nuclear magnetic resonance, electron paramagnetic resonance, thermogravimetric analysis, vibrating sample magnetometer) and physico-analytic techniques. Antidiabetic activities of synthesized complexes along with chalcones were evaluated by performing in vitro and in silico α-amylase and α-glucosidase inhibition studies. The obtained results displayed moderate to significant inhibition activity against both the enzymes by vanadyl chalcone complexes. The most potent complexes were further investigated for the enzyme kinetic studies and displayed the mixed inhibition for both the enzymes. Further, antioxidant activity of vanadyl chalcone complexes was evaluated for their efficiency to release oxidative stress using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay, and two complexes (Complexes 2 and 4) have demonstrated remarkable antioxidant activity. All the complexes were found to possess promising antidiabetic and antioxidant potential.
Synthesis and structure investigation of novel pyrimidine-2,4,6-trione derivatives of highly potential biological activity as anti-diabetic agent
Barakat, Assem,Soliman, Saied M.,Al-Majid, Abdullah Mohammed,Lotfy, Gehad,Ghabbour, Hazem A.,Fun, Hoong-Kun,Yousuf, Sammer,Choudhary, M. Iqbal,Wadood, Abdul
, p. 365 - 376 (2015)
Abstract Synthesis of (±)-1,3-dimethyl-5-(1-(3-nitrophenyl)-3-oxo-3-phenylpropyl)pyrimidine-2,4,6(1H,3H,5H)-trione (3) is reported. The structure of compound 3 was deduced by using spectroscopic methods, X-ray crystallography, and DFT calculations. The calculated geometric parameters were found to be in good agreement with the experimental data obtained from the X-ray structure. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and to study the different intramolecular charge transfer (ICT) interactions. The high LP(3)O6 →z BD?(2)O5-N3 ICT interaction energy (165.36 kcal/mol) indicated very strong n → π?electron delocalization while the small LP(2)O → BD?(1)C-H ICT interaction energies indicated that the C-H ... O intramolecular interactions are weak. The 1H and 13C NMR chemical shifts calculated using GIAO method showed good agreement with the experimental data. The calculated electronic spectra of the studied compound using TD-DFT method showed intense electronic transition band at 243.9 nm (f = 0.2319) and a shoulder at 260.2 nm (f = 0.1483) which were due to H-4/H-2/H-1/H → L+2 and H-5 → L electronic excitations, respectively. Compound 3 (IC50 = 305 ± 3.8 μM) was identified as a potent inhibitor of α-glucosidase in vitro and showed several fold more inhibition than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Molecular docking of the synthesized compound was discussed.
Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B
Iacovino, Luca G.,Pinzi, Luca,Facchetti, Giorgio,Bortolini, Beatrice,Christodoulou, Michael S.,Binda, Claudia,Rastelli, Giulio,Rimoldi, Isabella,Passarella, Daniele,Di Paolo, Maria Luisa,Dalla Via, Lisa
supporting information, p. 1151 - 1158 (2021/06/30)
A library of monosubstituted chalcones (1-17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases.
Double-edged Swords: Diaryl pyrazoline thiazolidinediones synchronously targeting cancer epigenetics and angiogenesis
Kumar, Alan P.,Meyer-Almes, Franz-Josef,Ramaa, C. S.,Safuan, Sabreena,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha
, (2021/09/22)
In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others. Compound 14b was most potent as evident by in-vitro and in-vivo biological assessments. It displayed anti-angiogenic potential by inhibiting endothelial cell proliferation, migration, tube formation and also suppressed new capillary formation in the growing chick chorioallantoic membranes (CAMs). It showed selectivity and potency towards HDAC4 as compared to other HDAC isoforms. Compound 14b (25 mg/kg, i.p.) also indicated exceptional antitumor efficacy on in-vivo animal xenograft model of human colorectal adenocarcinoma (HT-29). The mechanism of action of 14b was also confirmed by western blot.
Facile microwave-assisted synthesis and antitubercular evaluation of novel aziridine derivatives
Sarojini, Perumal,Jeyachandran, Malaichamy,Sriram, Dharmarajan,Ranganathan, Palraj,Gandhimathi
, (2021/02/26)
Novel 2-(aryloxymethyl)aziridines and 2-((3-aryl-1-phenylallyloxy)methyl)aziridine derivatives were prepared via ring-opening reaction of epoxides. The synthesized derivatives were characterized by using elemental analysis (EA), FT-IR, 13C NMR, and 1H NMR. The in vitro antitubercular activities of the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB H37Rv) strain using MTT-MABA assay. All the aziridine derivatives exhibited improved persuasive antitubercular activity against MTB H37Rv in comparison with standard drugs. Among the tested compounds, 2-(naphthalene-1-yloxy) methyl aziridine (5b), 2-(naphthalene-2-yloxy)methylaziridine (5c), 2-(m-tolyloxymethyl)aziridine (5e), 2-(3-(4-methoxyphenyl)-1-phenylalloxy)methylaziridine (12b) and 2-(3-(2-chlorophenyl)-1-phenylallyloxy)methylaziridine (12c) revealed promising activity against MTB H37Rv. Specifically, compound 5b and 12 b showed three-times more active (MIC = 0.5 μg/mL) than the standard drugs ethambutol (MIC = 1.56 μg/mL) and ciprofloxacin (MIC = 1.56 μg/mL).
Design, synthesis and evaluation of 2,4,6-substituted pyrimidine derivatives as BACE-1 inhibitor: Plausible lead for alzheimer’s disease
Jadhav, Hemant R.,Jain, Priti,Wadhwa, Pankaj K.
, p. 1194 - 1206 (2021/12/21)
Alzheimer’s disease is one of the most common neurodegenerative disorder afflicting a large mass of population. BACE-1 (β-secretase) is an aspartyl protease of the amyloidogenic pathway considered responsible for Alzheimer’s disease (AD). Since it catalyzes the rate-limiting step of Aβ-42 production from amyloid precursor protein (APP), its inhibition is considered a viable thera-peutic strategy. We have reported the design of small molecular weight compounds supposed to be blood brain permeable as BACE-1 inhibitors. The clue for the design of this series is drawn from the previously designed series from our research group. Objective: Design and synthesis of 2,4,6-substituted pyrimidine derivatives has been reported. In vitro FRET-based screening of synthesized derivatives was performed to evaluate the BACE-1 inhibition profile. Methods: Based on the docking simulation studies, a library of derivatives was designed, synthesized and evaluated for BACE-1 inhibition in-vitro. The docking studies were performed on Glide (Schrodinger suite) and Molegro virtual docker. Theoretical toxicity was predicted using Osiris Property Explorer. The synthesized compounds were tested for BACE-1 inhibition using in vitro assay based on Fluorescence Resonance Energy Transfer technique. The percent inhibition was cal-culated as a measure of activity. Results: The designed compounds revealed strong interactions with the desired amino acids of BACE-1 active sites. The aromatic rings placed at the fourth and sixth position of the pyrimidine ring occupied S1 and S3 substrate-binding clefts while the amino group formed hydrogen bonding interactions with Asp32 and Asp228. In silico data ensured that the compounds were orally bioavailable and brain permeable. The in vitro testing showed that the compounds inhibited BACE-1 at 10μM concentration. Conclusion: Compounds substituted with m-benzyloxy on one aromatic ring and o,p-di-chloro on another aromatic ring displayed maximum BACE-1 inhibition. Compound 2.13A displayed high docking score and was found to be most potent with IC50 of 6.92μM. The series displayed a good correlation between the docking score and BACE-1 inhibition profile.
Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia-derived cells: Role of PKCβ
Corsini, Emanuela,Facchetti, Giorgio,Esposito, Sara,Maddalon, Ambra,Rimoldi, Isabella,Christodoulou, Michael S.
, (2020/05/16)
In this study, a series of 20 chalcone derivatives was synthesized, and their antiproliferative activity was tested against the human T cell acute lymphoblastic leukemia-derived cell line, CCRF-CEM. On the basis of the structural features of the most active compounds, a new library of chalcone derivatives, according to the structure–activity relationship design, was synthesized, and their antiproliferative activity was tested against the same cancer cell line. Furthermore, four of these derivatives (compounds 3, 4, 8, 28), based on lower IC50 values (between 6.1 and 8.9 μM), were selected for further investigation regarding the modulation of the protein expression of RACK1 (receptor for activated C kinase), protein kinase C (PKC)α and PKCβ, and their action on the cell cycle level. The cell cycle analysis indicated a block in the G0/G1 phase for all four compounds, with a statistically significant decrease in the percentage of cells in the S phase, with no indication of apoptosis (sub-G0/G1 phase). Compounds 4 and 8 showed a statistically significant reduction in the expression of PKCα and an increase in PKCβ, which together with the demonstration of an antiproliferative role of PKCβ, as assessed by treating cells with a selective PKCβ activator, indicated that the observed antiproliferative effect is likely to be mediated through PKCβ induction.
Novel chalcones derivatives with potential antineoplastic activity investigated by docking and molecular dynamics simulations
Neto, Raimundo de A. M.,Santos, Cleydson B. R.,Henriques, Shayanne V. C.,Machado, Letícia de O.,Cruz, Jorddy N.,da Silva, Carlos H. T. de P.,Federico, Leonardo B.,Oliveira, Edivaldo H. C. de,de Souza, Michel P. C.,da Silva, Patrícia N. B.,Taft, Carlton A.,Ferreira, Irlon M.,Gomes, Madson R. F.
, (2020/11/12)
Glioblastoma is an aggressive primary tumor of the central nervous system (CNS). Is the most aggressive among infiltrative gliomas arising from the CNS. This tumor has low patient survival rate and several studies aiming at developing new drugs have increased. Patients with this cancer type face significant morbidity and mortality. This study evaluated the antineoplastic activity of synthetic chalcones (3a-3f) using in vitro glioblastoma models and molecular modeling. Cytotoxicity assay showed that Astrocitoma Hospital Ofir Loyola No 1 (AHOL1) and Uppsala 87 neoplastic glioblastoma lines (U87) cellular viability were significantly reduced compared to Healthy human fibroblasts cell lines (AN27) when exposed to chalcones. Interaction with the serine amino acid was present in the most promising and the reference binder docking, suggesting its importance inhibiting cell growth. Comparative analysis between the reference ligands and the molecules showed that the amino acid LYS352 present in all fittings, suggesting that this is the main amino acid for interaction with tubulin and are consistent with those in cytotoxicity assay, suggesting antineoplastic potential in glioblastoma. Long trajectory molecular dynamics studies were also carried out in order to investigate stability and conformations amongst the chalcones bound tubulin as well, in comparison to doxorubicin (here used as control), however future studies are needed to further assess the mechanism of inhibition of chalcones used in this investigation. Communicated by Ramaswamy H. Sarma.
Potassium Natural Asphalt Sulfonate (K-NAS): Synthesis and characterization as a new recyclable solid basic nanocatalyst and its application in the formation of carbon–carbon bonds
Falah, Saeid,Soleiman-Beigi, Mohammad,Kohzadi, Homa
, (2020/07/06)
In this research, we synthesized and characterized a new heterogeneous basic nanocatalyst and its catalytic application was studied in the Claisen-Schmidt and Knoevenagel condensations. In order to prepare this nanocatalyst, first, the Iranian natural asphalt was sulfonated with the concentrated sulfuric acid and then, converted to the potassium natural asphalt sulfonate (K-NAS). In order to characterization of the nanocatalyst, used of FT-IR spectroscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), inductively coupled plasma (ICP) and thermogravimetric analysis (TGA) techniques. This new basic heterogeneous nanocatalyst have advantages such as being eco-friendly, huge specific surface area, high reactivity and recyclability.
The Use of Modified Clay as an Efficient Heterogeneous and Ecofriendly Catalyst for the Synthesis of Chalcones via Claisen-Schmidt Condensation
Bentahar, S.,Dbik, A.,Khomri, M. El,Lacherai, A.,Messaoudi, N. El,Sabour, A.,Taleb, M. Ait
, p. 983 - 990 (2020/08/24)
Abstract: Clay modified by potassium fluoride (KF-modified clay) was used as an ecological alternative and heterogeneous catalyst for the preparation of chalcones via Claisen-Schmidt condensation. In this paper, we have synthesized classical chalcones by condensation of benzaldehyde substituents with acetophenone. Moreover, the other chalcones were also synthesized during the condensation of benzaldehyde substituents with 2-acetylfuran. All the results obtained show that our material can be used as an effective catalyst for the synthesis of chalcones with good yield included between 90 and 99%. The catalyst recycle study shows that the modified clay can be reused four times without a decrease in catalytic activity.
