31220-35-6Relevant academic research and scientific papers
Multi odd-even effects on cell parameters, melting points, and optical properties of chiral crystal solids based on S-naproxen
Tang, Gui-Mei,Wang, Jin-Hua,Zhao, Chao,Wang, Yong-Tao,Cui, Yue-Zhi,Cheng, Fei-Yue,Ng, Seik Weng
, p. 7258 - 7261 (2015)
A set of chiral crystal solids with odd and even numbers of carbon atoms based on S-naproxen, ester S-naproxen-R1 (R1 = H, methyl, ethyl, n-propyl, n-butyl, and n-amyl), has been prepared, alternatively crystallizing in the space groups P21 and P212121, respectively, which shows the multi odd-even effects on cell parameters, melting points, and optical properties.
Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models
ünal, G?khan,Atalay, P?nar,Ayd?n, ?mer,Dayan, Serkan,Han, M. ?hsan,Kü?ükgüzel, ?. Güniz,Tun?, Cansu ümran
, (2021)
Naproxen is a common non-steroidal anti-inflammatory drug, which is the most usually used propionic acid derivative for the treatment of many types of diseases. In this study, a series of novel (S)-Naproxen derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H–13C NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds were screened for anticancer activity against two different human breast cancer cell lines (MDA-MB-231 and MCF-7). Among them, (S)-2-(6-methoxynaphthalen-2-yl)-N'-{(E)-[2-(trifluoromethoxy)phenyl]methylidene} propanehydrazide (3a) showed the most potent anticancer activity against both cancer cell lines with a good selectivity (IC50 = 22.42 and 59.81 μM, respectively). Furthermore, the molecular modeling of these compounds was studied on Vascular Endothelial Growth Factor Receptor 2. Inhibition of VEGFR-2 and apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 3a by using Western Blotting. Apoptosis was also detected by staining with DAPI in fluorescence microscopy. Flow Cytometry analyses related to cell cycle phases showed that a dramatic increase in S and M phases was established compared to untreated control cells indicating the cancer cell cycle arrest. The anticancer activity of compound 3a was investigated in the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, in mice. Our results showed that compound 3a had anticancer activity and decreased the tumor volume in both low (60 mg/kg) and high (120 mg/kg) doses in mice.
Synthesis and pharmacological evaluation of condensed heterocyclic 6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives of naproxen
Amir, Mohammad,Kumar, Harish,Javed, Sadique A.
, p. 4504 - 4508 (2007)
Some 6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a-f and 5a-d) have been synthesized by cyclisation of 4-amino-5-[1-(6-methoxy-2-naphthyl)ethyl]-3-mercapto-(4H)-1,2,4-triazole (3) with various substituted aromatic acids and aryl/al
1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies
Hagras, Mohamed,Saleh, Marwa A.,Ezz Eldin, Rogy R.,Abuelkhir, Abdelrahman A.,Khidr, Emad Gamil,El-Husseiny, Ahmed A.,El-Mahdy, Hesham A.,Elkaeed, Eslam B.,Eissa, Ibrahim H.
, p. 380 - 396 (2021/12/24)
In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in?vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.
Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of New Thiosemicarbazide-Triazole Hybrid Derivatives of (S)-Naproxen
Gündüz, Miyase G?zde,Han, M. ?hsan,Ince, Ufuk,Kü?ükgüzel, ?. Güniz
, (2022/03/18)
The discovery of new antimicrobial molecules is crucial for combating drug-resistant bacterial and fungal infections that pose a dangerous threat to human health. In the current research, we applied a molecular hybridization approach to synthesize original thiosemicarbazide-triazole derivatives starting from (S)-naproxen (7a–7k). After structural characterization using FT-IR, 1H-NMR, 13C-NMR, and HR-MS, the obtained compounds were screened for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Candida albicans ATCC 10231 and their isolates, as well. Although all compounds were found to be moderate antimicrobial agents, in general, their antibacterial activities were better than antifungal effects. Among the tested compounds, 7j carrying nitrophenyl group on the thiosemicarbazide functionality represented the best MIC value against S. aureus isolate. Finally, molecular docking studies were performed in the active pocket of S. aureus flavohemoglobin to rationalize the obtained biological data.
Design of multifaceted antioxidants: Shifting towards anti-inflammatory and antihyperlipidemic activity
Kourounakis, Angeliki,Lambrinidis, George,Tzara, Ariadni
, (2021/08/30)
Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1-17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.
Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
Liu, Xiaolong,Zhao, Meng,Fan, Xinjiong,Fu, Yao
, p. 6126 - 6133 (2021/09/28)
Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite
Cheng, Xionglve,Jiang, Gangzhong,Li, Xingxing,Tao, Suyan,Wan, Xiaobing,Zhao, Yanwei,Zheng, Yonggao
supporting information, p. 2713 - 2718 (2021/06/25)
In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.
Manganese Catalyzed Hydrogenation of Enantiomerically Pure Esters
Widegren, Magnus B.,Clarke, Matthew L.
supporting information, p. 2654 - 2658 (2018/05/17)
A manganese-catalyzed hydrogenation of esters has been accomplished with TONs up to 1000, using cheap, environmentally benign, potassium carbonate and simple alcohols as activator and solvent, respectively. The weakly basic conditions lead to good functional group tolerance and enable the hydrogenation of enantiomerically enriched α-chiral esters with essentially no loss of stereochemical integrity.
Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase
Gérard, Doriane,Guéroult, Marc,Casas-Godoy, Leticia,Condoret, Jean-Stéphane,André, Isabelle,Marty, Alain,Duquesne, Sophie
, p. 433 - 441 (2017/03/24)
Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E?=?52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E???300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E???300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E???300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5?times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.
