1772-76-5Relevant academic research and scientific papers
Studies on crystal growth, vibrational, dielectric, electronic, mechanical and thermal properties of new organic nonlinear optical crystal: 3-nitrocinnamic acid
Alen,Sajan,Job Sabu,Udaya Lakshmi,Veeraiah,Chaitanya,Bena Jothy
, p. 9176 - 9188 (2013)
3-Nitrocinnamic acid (3NCA) was synthesized and its crystals were grown in aqueous solution by slow evaporation solution growth technique. The grown crystal was confirmed by powder XRD studies. The geometry, intermolecular hydrogen bonding, and harmonic vibrational wavenumbers of 3NCA were investigated with the help of B3LYP density functional theory (DFT) methods. The calculated molecular geometry has been compared with the experimental data obtained from XRD data. The assignments of the vibrational spectra have been carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). Vibrational spectral investigation confirms the formation of cyclic dimers in the crystal, with the carboxyl groups of each acid molecule bonded to those of adjacent molecules. The red shift of the O-H stretching wavenumber is due to the formation of strong O-H...O hydrogen bonds by hyperconjugation between the carbonyl oxygen lone electron pairs and the O-H σ* antibonding orbitals. Thermal stability of the grown crystal was examined by recording TGA/DTA. Mechanical strength of the grown material was tested by hardness studies. Second harmonic frequency generation was examined by Kurtz and Perry powder test and it reveals that the relative conversion efficiency is 0.8 times greater than that of urea. The theoretical first order hyperpolarizability value was calculated for the optimized structure.
Amine functionalized K10 montmorillonite: A solid acid-base catalyst for the Knoevenagel condensation reaction
Varadwaj, G. Bishwa Bidita,Rana, Surjyakanta,Parida
, p. 5122 - 5129 (2013)
Different amine functionalized K10 montmorillonites were hydrothermally fabricated by a simple method of treatment of the neat clay with different amine solutions and used as heterogeneous catalysts towards the Knoevenagel condensation reaction. Catalytic results show that the di-amine functionalized K10 montmorillonite exhibits high efficacy for promoting this reaction at room temperature and in the absence of a solvent. The solid catalyst was characterized using a variety of different techniques; including Fourier transform infrared spectroscopy (FT-IR), nitrogen physisorption measurements, 29Si CP MAS NMR spectroscopy, NH3-temperature programmed desorption (NH3-TPD), X-ray powder diffraction (XRD), and field emission scanning electron microscopy (FESEM). The catalyst could be recycled and reused for several runs without any loss of inherent catalytic activity.
Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
supporting information, p. 5905 - 5908 (2021/06/18)
A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
Design, synthesis, and evaluation of different scaffold derivatives against NS2B-NS3 protease of dengue virus
Ganji, Lata R.,Gandhi, Lekha,Musturi, Venkataramana,Kanyalkar, Meena A.
, p. 285 - 301 (2020/11/19)
The number of deaths or critical health issues is a threat in the infection caused by Dengue virus, which complicates the situation, as only symptomatic treatment is the current solution. In this regard we have targeted the dengue protease NS2B-NS3 that is responsible for the replication. The series was designed with the help of molecular modeling approach using docking protocols. The series comprised of different scaffolds viz. cinnamic acid analogs (CA1–CA11), chalcone (C1–C10) and their molecular hybrids (Lik1–Lik10), analogs of benzimidazole (BZ1-BZ5), mercaptobenzimidazole (BS1-BS4), and phenylsulfanylmethylbenzimidazole (PS1-PS4). Virtual screening of various natural phytoconstituents was employed to determine the interactions of designed analogs with the residues of catalytic triad in the active site of NS2B-NS3. We have further synthesized the selected leads. The synthesized analogs were evaluated for the cytotoxicity and NS2B-NS3 protease inhibition activity and compared with known anti-dengue natural phytoconstituent quercetin as the standard. CA2, BZ1, and BS2 were found to be more potent and efficacious than the standard quercetin as evident from the protease inhibition assay.
Design, synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase
Ghafary, Shahrzad,Ghobadian, Roshanak,Mahdavi, Mohammad,Nadri, Hamid,Moradi, Alireza,Akbarzadeh, Tahmineh,Najafi, Zahra,Sharifzadeh, Mohammad,Edraki, Najmeh,Moghadam, Farshad Homayouni,Amini, Mohsen
, p. 463 - 477 (2020/05/25)
Background: Acetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease. Methods: Colorimetric Ellman’s method was used for determination of IC50 value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action. Result and discussion: A new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC50 = 11.51?μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC50 = 1.95?μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10?μM. Conclusion: It is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. [Figure not available: see fulltext.]
New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation
Angeli, Andrea,Arifuddin, Mohammed,Singh, Priti,Supuran, Claudiu T.,Swain, Baijayantimala
, (2020/07/03)
Two novel series of phenylacrylamide linked coumarins and sulfocoumarins (6a-p, 8a-i, and 14a-g) were synthesized and evaluated against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, hCA II, hCA IX and hCA XII for their inhibitory action. All new compounds when screened for carbonic anhydrase inhibitory activity have shown selective inhibition towards the tumor associated isoforms hCA IX and XII over CA I and II, with inhibition constants in the submicromolar to low nanomolar range. Compound 6b and 14g exhibited significant inhibition with low nanomolar potency against hCA IX, whereas 6k was effective against hCA XII. Compounds 6b, 14g and 6k may be considered as lead molecules for future development of cancer therapeutics based on a novel mechanism of action.
Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase
Gie?el, Josephine M.,Serbian, Immo,Loesche, Anne,Csuk, René
, (2019/06/19)
Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Ki = 8.30 ± 0.94 μM and Ki′ = 9.54 ± 0.38 μM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Ki = 8.23 ± 0.93 μM and Ki′ = 13.07 ± 0.46 μM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).
Structure-aided drug development of potential neuraminidase inhibitors against pandemic H1N1 exploring alternate binding mechanism
Malbari, Khushboo D.,Chintakrindi, Anand S.,Ganji, Lata R.,Gohil, Devanshi J.,Kothari, Sweta T.,Joshi, Mamata V.,Kanyalkar, Meena A.
, p. 927 - 951 (2019/02/07)
Abstract: The rate of mutability of pathogenic H1N1 influenza virus is a threat. The emergence of drug resistance to the current competitive inhibitors of neuraminidase, such as oseltamivir and zanamivir, attributes to a need for an alternative approach. The design and synthesis of new analogues with alternate approach are particularly important to identify the potential neuraminidase inhibitors which may not only have better anti-influenza activity but also can withstand challenge of resistance. Five series of scaffolds, namely aurones (1a–1e), pyrimidine analogues (2a–2b), cinnamic acid analogues (3a–3k), chalcones (4a–4h) and cinnamic acid linkages (5a–5c), were designed based on virtual screening against pandemic H1N1 virus. Molecular modelling studies revealed that the designed analogues occupied 430-loop cavity of neuraminidase. Docking of sialic acid in the active site preoccupied with the docked analogues, i.e. in 430-loop cavity, resulted in displacement of sialic acid from its native pose in the catalytic cavity. The favourable analogues were synthesized and evaluated for the cytotoxicity and cytopathic effect inhibition by pandemic H1N1 virus. All the designed analogues resulting in displacement of sialic acid suggested alternate binding mechanism. Overall results indicated that aurones can be measured best among all as potential neuraminidase inhibitor against pandemic H1N1 virus. Graphical abstract: [Figure not available: see fulltext.].
Pyridazinone derivative, and preparation method and medical application thereof
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Paragraph 0158-0162, (2019/10/07)
The invention provides a pyridazinone derivative, and a preparation method and a medical application thereof. O-formylbenzoic acid used as a raw material reacts with dimethyl phosphite to obtain dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate, the dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate reacts with 3-cyano-4-fluorobenzaldehyde in the presence of triethylamine to prepare (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile, and the (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile is reduced by hydrazine hydrate to prepare 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid; and benzaldehyde or substituted aromatic formaldehyde or furfural used as a raw material and malonic acid undergo a Knoevenagel reaction to obtain cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid, the cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid and 1-tert-butoxycarbonylpiperazine undergo an amidation reaction, a tert-butoxycarbonyl group is removed from the obtained amidation product in the presence of trifluoroacetic acid, and the obtained product and the 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid undergo the amidation reaction to obtain a series of (E)-4-{3-[4-[(3-substituted aryl)acryloyl]piperazin-1-carbonyl]-4-fluorobenzyl}-2H-pyridazin-1-one derivatives. Results of preliminary pharmacological activity screening show that the compound represented by a general formula shown in the present invention has a certain in-vitro PARP-1 inhibition ability and a certain in-vitro tumor cell proliferation resisting activity. The structural general formula of compound is shown in the description; and in the general formula, Ar is selected from two formulas also shown in the description, and R1, R2, R3, R3, R4 and R5 can be the hydrogen atom, the fluorine atom, the chlorine atom, the bromine atom, a methyl group, a methoxy group, a tetrafluoromethyl group and a nitro group.
Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
Lu, Guo-qing,Li, Xin-yang,Mohamed O, Kamara,Wang, Depu,Meng, Fan-hao
, p. 282 - 296 (2019/03/27)
Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against four cancer cell lines (A549, OVCAR-3, SGC-7901, and HepG2) by the MTT assay. Most of them showed excellent activities against all the tested cell lines. Furthermore, hTS assay results showed that these compounds have the unique ability to inhibit hTS activity in vitro. Notably, compound 13j exhibited the most potent activity against A549 cells (IC50 = 1.18 μM) and extremely prominent enzyme inhibition (IC50 = 0.13 μM), which was superior to the pemetrexed (PTX, IC50 = 3.29 μM and IC50 = 2.04 μM). Flow cytometric analysis showed the compound 13j could inhibit A549 cells proliferation by arresting the cell cycle in the G1/S phase, then induced the cell apoptosis. Further western blot analysis showed that compound 13j could down-regulate the cycle checkpoint proteins cyclin D1 and cyclin E to inhibit the cell cycle progression, and then induce intrinsic apoptosis by activating caspase-3, and reducing the ratio of bcl-2/bax. All of these results demonstrated that this new structure has potential drug-making properties and provides new ideas for drug development.
