41283-72-1Relevant academic research and scientific papers
Site-Specific Oxidation of (sp3)C-C(sp3)/H Bonds by NaNO2/HCl
Zhao, Jianyou,Shen, Tong,Sun, Zhihui,Wang, Nengyong,Yang, Le,Wu, Jintao,You, Huichao,Liu, Zhong-Quan
supporting information, p. 4057 - 4061 (2021/05/26)
A site-specific oxidation of (sp3)C-C(sp3) and (sp3)C-H bonds in aryl alkanes by the use of NaNO2/HCl was explored. The method is chemical-oxidant-free, transition-metal-free, uses water as the solvent, and proceeds under mild conditions, making it valuable and attractive to synthetic organic chemistry.
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.
Phenyl substituted thiazole linked 1, 2, 4-triazole derivatives: Synthesis and their biological evaluation
Jain, Sonika,Dhall, Esha,Devi, Meenu,Sharma, Swapnil,Dwivedi, Jaya,Sahu, Sanjeev Kumar
, p. 727 - 734 (2021/09/30)
Synthesize and evaluate some phenyl substituted thiazole linked 1, 2, 4-triazole derivatives as antimicrobial agents. Compounds containing 1, 2, 4-triazole moieties are widely used as antimicrobial and antifungal agents whereas thiazole is another heterocyclic ring exhibiting various pharmacological actions. It is interesting to incorporate different bioactive pharmacophores in the same molecular framework to examine cumulative effect exerted by the moiety. This hypothesis was applied in research work by having triazole and thiazole in the same molecular framework. The present work was mainly focused on synthesis of some 1, 2, 4-triazole derivatives linking with phenyl substituted thiazole nucleus and their evaluation for biological activity. The compounds (8a-8j) were synthesized as per design scheme and elucidated their structures using different spectroscopic data of IR, 1HNMR, 13CNMR & mass spectroscopy. These synthesized derivatives were evaluated for their antibacterial activity using broth dilution assay. Further, mechanism of action of test compounds was examined using protein leakage assay. All the spectral data were confirmed the synthesis of phenyl substituted thiazole linked 1, 2, 4-triazole derivatives and some of them exhibited significant antimicrobial activity. Amongst all compound 8c showed most potent activity with lowest IC50 values 180 μg/ml and 120 μg/ml against S. aureus & amp; B. cereus respectively. Whereas compound 8j demonstrated strong inhibitory activities only against negative strains P. aeruginosa and E. coli with lowest IC50 values 240 μg/mL and 200μg/mL respectively.
Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
Fan, Xinjiong,Fu, Yao,Liu, Xiaolong,Zhao, Meng
, 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.
Ibuprofen-based chemosensor for efficient binding and sensing of Cu2+ ion in aqueous medium
Hooda, Sunita,Kumar, Pramod,Kumar, Vikrant,Lal, Shyam,Prakash, Kunal
, (2019/09/06)
An ibuprofen based molecular receptor R1 (N-[2-[(2-Hydroxy-benzylidene)-amino]-ethyl]-2-(4-isobutyl-phenyl)-propionamide) was developed for the detection of Cu2+ ion in aqueous medium by absorbance and fluorescence techniques. Binding constants (4.89–5.67 × 103 M?1) and detection limits (1.71–2.12 μM) showed significant sensing ability. SEM and PXRD techniques were employed to establish the complex formation between R1 and Cu2+ ion and also showed promising behaviour of nanomaterial. The competitive binding experiments showed the selectivity of Cu2+ ion in presence of other metal ions in aquoues medium. The reversibility studies for chemosensor R1 was investigated and EDTA used as restoring agent. The strong chelation through –N and –O atoms of receptor R1 enhance the change in color triggered selectively by Cu2+ ion and detected by colorimetric methods. The theoretical calculations were employed in order to confirm the experimental observations in the molecular frames.
Radical dehydroxylative alkylation of tertiary alcohols by Ti catalysis
Xie, Hao,Guo, Jiandong,Wang, Yu-Quan,Wang, Ke,Guo, Peng,Su, Pei-Feng,Wang, Xiaotai,Shu, Xing-Zhong
supporting information, p. 16787 - 16794 (2020/11/09)
Deoxygenative radical C?C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10-g-scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C?OH bond.
Carbonic anhydrase inhibitory potential of 1,2,4-triazole-3-thione derivatives of flurbiprofen, ibuprofen and 4-tert-butylbenzoic hydrazide: Design, synthesis, characterization, biochemical evaluation, molecular docking and dynamic simulation studies
Abbas, Saghir,Abbas, Syed M.,Ali, Saqib,Hameed, Shahid,Iqbal, Jamshed,Munawar, Khurram S.,Shaheen, Farzana,Tahir, Muhammad N.,Ur Rahman, Shafiq,Zaib, Sumera
, p. 298 - 310 (2019/07/12)
Background: The over-expression of the carbonic anhydrases results in some specific carcinomas including pancreatic, gastric and brain tumor. Tumors are distinguished under hypoxic conditions and various investigations are being carried out to target the known hypoxic areas of the tumors to increase the sensitivity towards standard therapeutic treatment. Objective: Herein, we have designed and synthesized some biologically important esters, hydrazides, thiocarbamates, 1,2,4-triazole-3-thiones and Schiff bases. The purpose of the research was to evaluate the derivative against carbonic anhydrase and to assess the toxicity of the same compounds. Method: The structures of all the compounds were characterized by FT-IR, mass spectrometry, elemental analysis, 1H and 13C NMR spectroscopy. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase II by in vitro assay. Double reciprocal plots for inhibition kinetics of the potent compounds were constructed and mode of inhibition was determined. Furthermore, to check the cytotoxicity, these derivatives were tested against human breast adenocarcinoma by MTT method. Results: X-ray diffraction analysis of the compounds 10, 14 and 15 showed that they did not have any φ-φ or C-H…φ interactions. The experimental results were validated by molecular docking and dynamic simulations of the potent compounds in the active pocket of enzyme. Important binding interactions of potent compounds with the key residues in the active site of the carbonic anhydrase enzyme were revealed. Drug likeness profile of the derivatives was evaluated to determine the physicochemical properties. Conclusion: The proposed synthetic approach provides a suitable platform for the generation of a new library of compounds which could potentially be employed in the future testing and optimization of inhibitor potencies.
Synthesis and Evaluation of Some Phenyl Substituted Azetidine Containing 1, 2, 4-triazole Derivatives as Antibacterial Agents
Dhall, Esha,Jain, Sonika,Mishra, Achal,Dwivedi, Jaya,Sharma, Swapnil
, p. 2859 - 2869 (2018/11/10)
A novel series of phenyl substituted azetidine containing 1, 2, 4-triazole derivatives 7(a–j) were synthesized and characterized by IR, 1HNMR, 13CNMR, and mass spectroscopy. Synthesized 1, 2, 4-triazole derivatives were subsequently assayed in vitro to investigate their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli using broth dilution method. Compounds 7c, 7d, and 7e exhibited potent inhibitory activities as compared to standard cefotaxime. Further, fluorescence spectral studies were also carried out to ascertain the antibacterial potential of compound 7c against two bacterial strains, that is, P.?aeruginosa and S.?aureus. In docking studies, all the compounds exhibited good docking scores between ?12.04 and ?11.36?kcal/mol and indicated that compounds could act through inhibition of bacterial DNA gyrase (PDB ID 3U2D). Among all, 7c has shown the maximum docking score and found in agreement to in vitro studies. In conclusion, synthesized 1, 2, 4-triazole derivatives holds substantial caliber to be categorized as antibacterial agents.
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.
Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents
Amir, Mohd,Akhter, Mohd Wasim,Alam, Ozair
, p. 493 - 508 (2016/03/19)
A series of furoxan-based nitric oxide releasing ibuprofen derivatives were synthesized and tested for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, and hepatotoxic properties. The compounds exhibited more protection than ibuprofen with regard to gastric toxicity. Among the tested compounds 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan and 4-[2-[2-(4-isobutylphenyl)propanoyl]hydrazinecarbonyl]-3-phenylfuroxan emerged as most active anti-inflammatory agents with reduced gastrotoxicity. The results showed that incorporation of NO donating group caused a moderate increase in anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent drug ibuprofen. A molecular docking study of all the compounds was also performed to provide the binding modes of COX-1 enzyme. Among all the titled compounds, 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan was found to be most potent and have high docking score showing favorable orientation within the COX-1 binding site.
