940-64-7Relevant academic research and scientific papers
Design, docking, synthesis, and characterization of novel N'(2-phenoxyacetyl) nicotinohydrazide and N'(2-phenoxyacetyl)isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents
Al-Ostoot, Fares Hezam,Khanum, Shaukath Ara,M, Pallavi H,Vivek, Hamse Kameshwar
, (2021/09/14)
Inflammation is the complex biological response of vascular tissues, which is partly determined by prostaglandins (PLA2). The cyclooxygenase (COX) enzyme exists in two isoforms: COX-1 and COX-2 and by the action of this, the PGs are produced. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) are therapeutic agents useful in the treatment of inflammation. Encouraged by this, the new derivatives of N'(2-phenoxyacetyl)nicotinohydrazide 9(a-e) and N'(2-phenoxyacetyl)isonicotinohydrazide 10(a-e) were designed, synthesized, characterized, and identified as remarkable anti-inflammatory and analgesic agents. These compounds were prepared in a series of steps starting with different phenol derivatives. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2SI. Further, molecular Docking Studies have been performed for the potent compound to check the three-dimensional geometrical view of the ligand binding to the targeted enzymes.
Juvenile hormone mimics with phenyl ether and amide functionality to be insect growth regulators (IGRs): synthesis, characterization, computational and biological study
Awasthi, Pamita,Devi, Vandna
, (2021/10/12)
A series of substituted phenyl ethers derivatives as juvenile hormone (JH) mimics (V1-V8) have been synthesized. Substituted phenoxyacetic acid and amino acid ethyl ester hydrochloride were prepared using NaOH, SOCl2. DCC method has been used for amide linkage. The structure of prepared compounds has been confirmed by Fourier Transform Infra-Red (FT-IR), Electrospray ionization-Mass spectrometry (ESI-MS), Proton and Carbon-13 nuclear magnetic resonance (1H-NMR, 13C-NMR) spectroscopic techniques. Biological efficacy of synthesized analogs has been carried out under laboratory conditions. Galleria mellonella (honey bee pest) has been chosen as testing insect. Juvenile hormone (JH) activity of synthesized compounds has been tested at different concentrations and compared with the standard juvenile hormone analogs (JHAs) pyriproxyfen (M1) and fenoxycarb (M2) against the fifth larval instar of G. mellonella. Compound ethyl 2-[2-(4-methylphenoxy)aminoacetyl]-3-phenyl-propanoate (V6) exhibited better activity among all the synthesized compounds (V1-V8) with LC50 and LC90 values of 0.11 mg/mL and 0.56 mg/mL respectively. Compounds showed insect growth regulating (IGR) activity at lower concentrations. In silico screening of all synthesized compounds with the W-cavity of juvenile hormone-binding protein (JHBP) of insect G. mellonella has been carried out. Chemical reactivity of synthesized series has been studied using DFT/B3LYP/6-311 + G(d,2p) method. Non-toxic behavior of molecules has also been observed from ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) study using discovery studio client 3.0. Communicated by Ramaswamy H. Sarma.
Synthesis, crystal structure characterization, DFT calculations, Hirshfeld surface analysis and 3D energy frameworks of triazole pyridazine derivatives: Theoretical and experimental studies
Al-Ostoot, Fares Hezam,Khanum, Shaukath Ara,M. A., Sridhar,Mohammed, Yasser Hussien Issa,Sallam, Hamdi Hamid
, (2021/09/04)
Recently, pyridazine derivatives have shown considerable biological properties such as anti-tumor and anti-inflammatory activity. The studied compounds 6-chloro-3-[(4-methylphenoxy)methyl][1,2,4] triazolo[4,3-b]pyridazine (8a) and 6-chloro-3-[(4-fluorophenoxy)methyl][1,2,4] triazolo[4,3-b]pyridazine (8b) have been synthesized and characterized by NMR, IR and mass spectral studies, and finally, the structures were confirmed by single crystal X-ray diffraction technique. The compounds 8a and 8b have crystallized in the same crystal system with different space groups. Density functional theory calculations were performed to compare the theoretical and experimental results obtained from XRD. Further, DFT calculations were employed to determine HOMO-LUMO energy levels, energy gap, softness, hardness, and other quantum chemical parameters of the compounds 8a and 8b. Hirshfeld surface analysis was carried out to distinguish the different intermolecular hydrogen bonds. Energy frameworks for the compounds were constructed through different intermolecular interaction energies to know the dominant interaction energy involved in the molecular packing strength.
Synthesis, structural analysis, Hirshfeld surface analysis, DFT calculations, in vitro and docking study on antioxidant activity of 6-chloro-3-[(4-methylphenoxy) methyl] [1,2,4] triazolo[4,3-b]pyridazine
Sallam, Hamdi Hamid,Mohammed, Yasser Hussien Eissa,Geetha,Al-Ostoot, Fares Hezam,Sridhar,Shaukath, Ara Khanum
, p. 25 - 44 (2021/09/22)
Pyridazine nuclei are essential elements of many natural and synthetic compounds with important biological activities. NMR and IR, as well as studies of mass spectrum, were emplyed to synthesize and characterize the title compound 6-chloro-3-[(4-methylphenoxy) methyl] [1,2,4] triazolo[4,3-b] pyridazine (CMTP). The structure of this compound was confirmed by using single crystal X-ray diffraction technique and it got crystallized in the monoclinic crystal system with the space group P2 1/c. The values of unit cell parameters are: a = 12.0965(7) ?, b = 13.6075(7) ?, c = 7.7686(4) ?, β = 93.942(3)° and Z = 4. Intermolecular hydrogen bonds of two types i.e., C-H…O and C-H…N, were noticed. Hirshfeld surface analysis was employed to account for these interaction bonds. Energy frameworks were carried out to know the dominant interaction energy involved in the molecular packing. DFT calculations were constructed to find the agreement between the theoretical and experimental values. HOMO-LUMO energy levels have been determined; global hardness, global softness, and other quantum chemical parameters have been calculated to reveal the chemical reactivity of the compound. In order to investigate the antioxidant activity of the compound, molecular docking studies were performed.
Effect of o-difluoro and p-methyl substituents on the structure, optical properties and anti-inflammatory activity of phenoxy thiazole acetamide derivatives: Theoretical and experimental studies
Khamees, Hussien Ahmed,Mohammed, Yasser Hussein Eissa,S, Ananda,Al-Ostoot, Fares Hezam,Y, Sangappa,Alghamdi, Saad,Khanum, Shaukath Ara,Madegowda, Mahendra
, (2019/09/18)
Thiazole derivatives (6a and 6b) have been synthesized and characterised by 1H –13C NMR, as well as LC-MS spectra. The three-dimensional structures have been confirmed by single crystal X-ray diffraction method. 6a and 6b compounds have been crystallized in the Triclinic and the Orthorhombic systems with P-1 and Pbca space groups, respectively. Supramolecular structures revealed the stability of molecules with different intermolecular interactions and different crystal packing environment. Theoretical study by Density functional theory (DFT) with B3LYP functional based on highest basis set 6–311++G(d,p) was employed to calculate the geometry and compared to the experimental data. The electronic structures and intramolecular charge transfers have been investigated by using natural population and natural bond orbital analysis (NBO). Further, DFT studies were performed to assess the frontier molecular orbitals (FMOs), energy gap, softness, hardness, and others chemical reactivity. Hirshfeld surface was investigated to distinguish the different interatomic contacts and understand the crystal packing of molecules with aid of energy frameworks through different intermolecular interaction energies based on the anisotropy of the topology. Nonlinear optical property (NLO) of the synthesized molecules were predicted by (DFT) and examined experimentally by using second harmonic generation (SHG) and revealed the importance of high NLO based on the nature of substituents and conformation. Thiazole derivatives were assessed for anti-inflammation activity by in silico molecular docking studies against COX-1 and COX-2 protein receptors revealed prominent interactions with active site and further molecular dynamics confirms the stability of the protein-ligand model. In vitro assay against cyclooxygenase (COX) enzyme gave IC50 values of 6a and 6b molecules with ortho-difluoro and para-methyl positions on benzoyl group, showed better inhibitor for COX-1 and COX-2, respectively.
Effective removal of calcium and magnesium sulfates from wastewater in the rare earth industry
Wang, Yanliang,Guo, Xiangguang,Bai, Yan,Sun, Xiaoqi
, p. 33922 - 33930 (2019/11/11)
The wastewater discharged from the rare earth (RE) industry generally contains a high level of calcium and magnesium sulfates, which confers permanent hardness and causes difficulties in recycling this wastewater. In this study, the alkyl phenoxy acetic acid derivatives including 4-methyl phenoxy acetic acid (M-POAA), 4-tert-butyl phenoxy acetic acid (B-POAA) and 4-tert-octyl phenoxy acetic acid (O-POAA), were synthesized via the Williamson reaction and characterized by nuclear magnetic resonance (NMR), infrared (IR), and ultra-violet (UV) spectroscopy, as well as elemental analysis and X-ray diffraction (XRD). Synthesis of the POAAs were simple and green, and the raw materials used for their production are widely available and low-cost. The potential for removal of Ca and Mg sulfates from industrial wastewater using POAAs as the organic precipitants was assessed. The total precipitation efficiencies of Ca and Mg from wastewater with the use of POAAs increased with the following order: M-POAA -1, respectively. The O-POAA could be regenerated five times without any significant change in its structure and precipitation performance. Thus, the use of the novel precipitants is a prospective alternative to the conventional processes for softening wastewater.
PRMT5 INHIBITORS AND USES THEREOF
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, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
Design and Synthesis of Novel 4-Hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one Derivatives for Use as Herbicides and Evaluation of Their Mode of Action
Lei, Kang,Li, Pan,Yang, Xue-Fang,Wang, Shi-Ben,Wang, Xue-Kun,Hua, Xue-Wen,Sun, Bin,Ji, Lu-Sha,Xu, Xiao-Hua
, p. 10489 - 10497 (2019/10/02)
In order to develop a novel herbicide containing the β-triketone motif, a series of 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one derivatives were designed and synthesized. The bioassay results showed that compound II15 had good pre-emergent herbicidal activity even at a dosage of 187.5 g ha-1. Moreover, compound II15 showed a broader spectrum of weed control when compared with a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), and displayed good crop safety to Triticum aestivum L. and Zea mays Linn. when applied at 375 g ha-1 under pre-emergence conditions, which indicated its great potential as a herbicide. More importantly, studying the molecular mode of action of compound II15 revealed that the novel triketone structure is a proherbicide of its corresponding phenoxyacetic acid auxin herbicide, which has a herbicidal mechanism similar to that of 2,4-D. The present work indicates that the 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one motif may be a potential lead structure for further development of novel auxin-type herbicides.
Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones
Wang, Zexu,Wu, Xiaofan,Li, Zhining,Huang, Zedu,Chen, Fener
supporting information, p. 3575 - 3580 (2019/04/14)
We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L?1 d?1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.
ROLES OF MODULATORS OF INTERSECTIN-CDC42 SIGNALING IN ALZHEIMER'S DISEASE
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Paragraph 0272; 0275; 0276, (2019/04/14)
Methods of treating Alzheimer's disease and other neurodegenerative and/or neurocognitive and/or neurodevelopmental diseases are described. The methods comprise the administration of compounds that modulate an activity of cell division control protein 42 (Cdc42), such as the interaction between Cdc42 and intersectin (ITSN). Exemplary modulator compounds include thioureas, disulfonamides of fused aromatic systems (e.g., benzofuran), and acyl hydrazones, among others. Some of the modulator compounds act as activators of Cdc42, while others act as inhibitors. In some cases, the modulator compound has dual functionality and the ability of the modulator compound to act as an inhibitor or activator depends on whether or not Cdc42 is already activated in a particular disease stage or biological environment by an upstream activating signal of Cdc42.
