3-氨磺酰苯甲酸类AKR1C3抑制剂的3D-QSAR和分子对接研究

醛酮还原酶1C3(AKR1C3)作为治疗前列腺癌的新靶点已成为研究热点,3-氨磺酰苯甲酸衍生物对其具有高效的选择性和抑制活性。本文采用比较分子场分析(COMFA)和比较分子相似性指数分析(COMSIA)方法,将经分子对接后的34个优势构象组成训练集和11个优势构象组成测试集,构建三维定量构效关系(3D-QSAR)模型。COMFA模型的交叉验证系数(q2),非交叉验证系数(R2),标准偏差(SEE)和F值分别为0.761,0.973,0.122,185.963;自举法回归系数为R2bs=0.98。最佳组合COMSIA模型的q2,R2,SEE,F和R2bs分别为0.734,0.984,0.097,147.850,0.994。COMFA和COMSIA模型的系统外部测试R2pred分别为0.864和0.756,r2m分别为0.8127和0.5377。这些结果表明,所建立的QSAR模型具有较高的可靠性和较强预测能力。经三维等势图分析可知,在2、5或6位适当增加取代基体积,或在5位引入氢键受体,或在7位引入负电性取代基则能提高化合物的生物活性。该模型为进一步设计具有更优选择性和活性的化合物提供了理论依据。     

苯并咪唑类缓蚀剂的3D-QSAR研究及分子设计

采用比较分子场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA), 对苯并咪唑衍生物抗盐酸腐蚀的缓蚀性能进行了三维定量构效关系研究, 并使用留一法交叉验证手段对3D-QSAR模型的稳定性及预测能力进行了分析. 结果表明, 立体场、静电场和氢键供体场(电子给体)是影响苯并咪唑缓蚀剂缓蚀性能的主要因素; 所构建的CoMFA模型(q2=0.541, R2=0.996)和CoMSIA模型(q2=0.581, R2=0.987)均具有较好的统计学稳定性和预测能力. 基于3D-QSAR等势图设计出了几种具有较好缓蚀性能的苯并咪唑化合物, 为油气田新型缓蚀剂的研发提供了一种新思路.     

Synthesis and Characterization of Some Novel Thiazole Derivatives and Their Applications as Corrosion Inhibitors for Zinc in 1 M Hydrochloric Acid Solution

Russian Journal of Electrochemistry - The influence of corrosion inhibition of some thiazole derivatives, namely: 2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole-1-yl)thiazol-5(4H)-one,...     

Synthesis and structure of some substituted 2-amino-4-aryl-7-propargyloxy-4H-chromene-3-carbonitriles

A series of 2-amino-7-hydroxy-4H-chromene-3-carbonitriles 4a–l were synthesized through three-component reaction using sodium carbonate as a catalyst. The reaction was carried out in 96% ethanol-water medium (1:20 ratio in volume). Propargyl ether compounds 5a–l of these chromene-3-carbonitriles were successfully synthesized from corresponding hydroxyl chromene derivatives by reaction with propargyl bromide. Two different procedures were applied in this process: the procedure that used potassium carbonate in dried acetone and the procedure that used sodium hydride in dried DMF. The latter gave the ethers 5a–l in higher yields. The single-crystal X-ray structure of propargyl ether 5g has been recorded.     

Synthesis and Characterization of Some Amino Acid Derived Schiff Bases Bearing Nonionic Species as Corrosion Inhibitors for Carbon Steel in 2N HCl

A novel series of nonionic amino acid Schiff-Bases were synthesized and characterized using different spectroscopic tools to elucidate their chemical structures. The surface and thermodynamic properties of these compounds were studied using classical measurements including surface and interfacial tension and emulsification tendency. The surface parameters of these compounds including surface tension, critical micelle concentration (CMC), effectiveness (π_cmc), efficiency (Pc₂₀), maximum surface excess (Γ_max), and minimum surface area (A_min) showed their good surface activity. Their thermodynamic parameters of adsorption and micellization including free energy change of micellization and adsorption showed their tendency toward adsorption at the interfaces and also micelle formation at lower concentrations. The synthesized compounds were also evaluated as corrosion inhibitors for carbon steel at different doses (400, 200, 100, 50, and 25 ppm) in 2 N HCl using gravimetric technique (weight loss). The results showed that these inhibitors are characterized by very high corrosion inhibition efficiency ranged between 99.93% and 97.98% and low corrosion rates varied between 0.09 mpy and 0.17 mpy for higher doses (400 ppm). The efficiency of inhibition was decreased by increasing the exposure time. The most efficient corrosion inhibitor of the synthesized compounds was the inhibitor which contains polyethylene oxide chain length of 23 EO units and alkyl chain length of 12 methylene groups. The effect of the hydrophobic and hydrophilic chain length in the inhibitor molecules was discussed and rationalized with their inhibition efficiency. The tendency of these inhibitors toward complexation with the transition metals was also discussed in order to explain their higher efficiency.     

Synthesis and Evaluation as Glycosidase Inhibitors of 1H-Imidazol-2-yl C-Glycopyranosides

The (1H-imidazol-2-yl)ulose 8 and the 1H-imidazol-2-yl C-glycopyranosides 23 and 24 have been prepared from tetra-O-benzylgluconolactone 6 in two and six steps, respectively. The imidazoles 8 and 24 are moderate competitive inhibitors of sweet-almond β-glucosidase (pH 6.8, K_i ≈ 0.79 and 0.64 mM , respectively), while 23 is a competitive inhibitor of yeast α-glucosidase (pH 6.8, K_i ≈ 0.26 mM ). Addition of 2-lithiated 1-[(dimethylamino)methyl]-1H-imidazole to 6 gave the ulose 7 (68%), which was deprotected to 8 . Reduction of 7 with NaBH₄ yielded a 12:88 mixture 10/11 . Attempts to selectively mesylate HO? C(1) of these diols failed, while dinitrobenzoylation led to 19/20 , which cyclized easily (NaH) to a 25:75 mixture of 21 and 22 which were separated and debenzylated to the C-glycosides 23 and 24 .     

Synthesis of 3-Aryl-3-(Furan-2-yl)Propanoic Acid Derivatives,and Study of Their Antimicrobial Activity

Reactions of 3-(furan-2-yl)propenoic acids and their esters with arenes in Brønsted superacid TfOH affords products of hydroarylation of the carbon–carbon double bond, 3-aryl-3-(furan-2-yl)propenoic acid derivatives. According to NMR and DFT studies, the corresponding O,C-diprotonated forms of the starting furan acids and esters should be reactive electrophilic species in these transformations. Starting compounds and their hydroarylation products, at a concentration of 64 µg/mL, demonstrate good antimicrobial activity against yeast-like fungi Candida albicans. Apart from that, these compounds suppress Escherichia coli and Staphylococcus aureus.     

Pyridinium Halides and Their Mixtures as Inhibitors of Steel Corrosion in Sulfuric Acid Solutions

Mixtures of 1-acylmethylpyridinium halides with equimolar amounts of pyridinium halides were prepared by the Ortoleva-King reaction. The inhibiting effect of various pyridinium halides and their mixtures on corrosion of steel in sulfuric acid solutions was studied.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 517–519.Original Russian Text Copyright © 2005 by Yurchenko, Ivashchenko, Pilipenko, Pogrebova.     

苯并咪唑类缓蚀剂的HQSAR研究及分子设计

采用分子全息定量构效关系(HQSAR)方法, 构建苯并咪唑衍生物在酸性环境中的缓蚀性能与结构之间的定量构效关系模型, 研究不同碎片区分参数及碎片大小对模型质量的影响, 寻找最优HQSAR模型, 并对其稳定性及预测能力进行评价. 结果显示: 选取碎片区分参数为原子类型(A)、化学键类型(B)、连接性(C)、氢原子(H)、手性(Ch)、氢键给体和受体(D&;A), 碎片大小为1-3 建模时, 得到的HQSAR 模型(r²(非交叉验证系数)=0.996, q²(交叉验证系数)=0.960, SE_cv(交叉验证标准误差)=3.709)具有良好的统计学稳定性及预测能力. 根据最优HQSAR模型图设计出的38种苯并咪唑类化合物理论上均具有较好的缓蚀性能. 本研究为油气田新型高效缓蚀剂研发提供可靠的理论依据.     

Croton lechleri Extracts as Green Corrosion Inhibitors of Admiralty Brass in Hydrochloric Acid

Croton lechleri, commonly known as Dragon’s blood, is a tree cultivated in the northwest Amazon rainforest of Ecuador and Peru. This tree produces a deep red latex which is composed of different natural products such as phenolic compounds, alkaloids, and others. The chemical structures of these natural products found in C. lechleri latex are promising corrosion inhibitors of admiralty brass (AB), due to the number of heteroatoms and π structures. In this work, three different extracts of C. lechleri latex were obtained, characterized phytochemically, and employed as novel green corrosion inhibitors of AB. The corrosion inhibition efficiency (IE%) was determined in an aqueous 0.5 M HCl solution by potentiodynamic polarization (Tafel plots) and electrochemical impedance spectroscopy, measuring current density and charge transfer resistance, respectively. In addition, surface characterization of AB was performed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy techniques. Chloroform alkaloid-rich extracts resulted in IE% of 57% at 50 ppm, attributed to the formation of a layer of organic compounds on the AB surface that hindered the dezincification process. The formulation of corrosion inhibitors from C. lechleri latex allows for the valorization of non-edible natural sources and the diversification of the offer of green corrosion inhibitors for the chemical treatment of heat exchangers.     

Carmine and Fast Green as Corrosion Inhibitors for Mild Steel in Hydrochloric Acid Solution

The inhibition action of carmine and fast green dyes on corrosion of mild steel in 0.5 M HCl was investigated using mass loss, polarization and electrochemical impedance (EIS) methods at 300 K. The inhibition efficiency was found to increase with increasing concentration of the inhibitors. The inhibition efficiency of fast green (%η - 98) is higher than that of carmine (%η - 92) and found to be maximum in 1 × 10^-3 M solution. The inhibitors act as mixed type with predominant cathodic effect. The inhibitors were adsorbed on the mild steel surface according to the Temkin adsorption isotherm. The surface morphology of the mild steel specimens was evaluated using SEM images.     

Synthesis of Pyrrolidine Analogues of N-Acetylneuraminic Acid as Potential Sialidase Inhibitors

The pyrrolidine derivatives 3 , 4 , and 5 were prepared from the methyl ester 7 of Neu2en5Ac via lie pyrrolidine-borane adduct 33 . They inhibit Vibrio cholerae sialidase competitively with K_i = 4. 4 10^?3 M, 5. 3 10^?3 M, and 4. 0 10^?2 M, respectively. Benzylation of 7 gave the fully O-benzylated 8 besides 9, 10 , and 11. Ozonolysis and reduction with NaBH₄ of 8 and 9 gave the 1, 4-diols 12 and 15 , the hydroxy acetates 13 and 16 , and the furanoses 14 and 17 (Scheme 1), respectively. The diol 12 was selectively protected (→ 19 → 20 → 23 ) and transformed into the azide 27 by a Mitsunobu reaction. Selective base-catalysed deprotection of the diacetate 22 , obtained from 12 , was hampered by an easy acetyl-group migration. The mesylate 28 proved unstable. The azide 27 was transformed via 29 into the ketone 30 (Scheme 2). Hydrogenation of 30 gave the dihydropyrrole 31 and, hence, the pyrrole 32. The adduct 33 was obtained from 30 by a Staudinger reaction (→31) and reduction with LiBH₄/HBF⁴. It was transformed into the pyrroudine 34 . The structure of 34 was established by X-ray analysis. Reductamination of the pyrrolidine-borane adduct with glyoxylic acid gave 40 and, hence, 3. N-Alkylation afforded 44 and, hence, the phosphonate 4. The acid 5 was obtained from 33 by acylation (→ 47 ) and deprotection (Scheme 4).     

Correction to: Aziridine-2-Carboxylic Acid Derivatives and Its Open-Ring Isomers as a Novel PDIA1 Inhibitors

Chemistry of Heterocyclic Compounds -     

Performance and Mechanism of Alkylimidazolium Ionic Liquids as Corrosion Inhibitors for Copper in Sulfuric Acid Solution

The addition of corrosion inhibitors is an economic and environmental protection method to prevent the corrosion of copper. The adsorption, performance, and mechanism of three 1-alkyl-3-methylimidazolium hydrogen sulfate ([BMIM]HSO₄, [HMIM]HSO₄, and [OMIM]HSO₄) ionic liquids (ILs) on the copper surface in 0.5 M H₂SO₄ solutions were studied by quantum chemical calculation, quantitative structure-activity relationship (QSAR), and molecular dynamics simulation. It is found that the main reactive site is located on the imidazolium ring (especially the C2, N4, and N7 groups). When the alkyl chain of the imidazolium ring is increasing, the molecular reactivity of the ILs and the interaction between the ILs inhibitor and copper surface are enhanced. The imidazole ring of the ILs tends to be adsorbed on Cu (111) surface in parallel through physical adsorption. The order of adsorption energy is [Bmim]HSO₄ < [Hmim]HSO₄ < [OMIM]HSO₄, which is in agreement with the experimental order of corrosion efficiency. On the imidazole ring, the interaction between the copper surface and the C atom is greater than that between the copper surface and the N atom. It is found that ILs addition can hinder the diffusion of corrosion particles, reduce the number density of corrosion particles and slow down the corrosion rate. The order of inhibition ability of three ILs is [Bmim]HSO₄ < [Hmim]HSO₄ < [OMIM]HSO₄,which agree well with experimental results. A reliable QSAR correlation between the inhibition corrosion efficiency and molecular reactivity parameters of the ILs was established.     

Electrochemical and Quantum Chemical Studies of Azoles as Corrosion Inhibitors for Mild Steel in Hydrochloric Acid

The inhibition effect of three azole compounds, 2-aminobenzimidazole(ABM), 2-aminothiazole(AT) and 2-aminobenzothiazole(ABT), on the corrosion of mild steel in a 1 mol/L HCl solution was investigated by means of potentiodynamic polarization measurement, electrochemical impedance spectroscopy(EIS) and scanning electron mi-croscopy(SEM). The correlation between inhibition efficiency and molecular structure of inhibitor was theoretically studied via quantum chemical calculations. The results show that the inhibition efficiency(η) of the inhibitors follows the order of η_ABT >η_AT >η_ABM. Moreover, ABM, AT and ABT belong to mixed-type inhibitors. The adsorption of the inhibitors on the steel surface follows the Langmuir adsorption isotherm, with both physisorption and chemisorption.     

Synthesis and Antimicrobial Activity of N,N-Disubstituted 3-Allyloxy-1-amino-2-propanethiols

3-Allyloxy-1,2-epithiopropane was synthesized; its treatment with amines yielded N,N-disubstituted 3-allyloxy-1-amino-2-propanethiols, which were tested for antimicrobial activity.     

Synthesis of Some Benzimidazole‐based Heterocycles and their Application as Copper Corrosion Inhibitors

A series of new substituted benzimidazoles embedded with a variety of function groups has been synthesized from N‐methyl‐2‐bromoacetylbenzimidazole. The synthesized compounds were fully characterized, and their structures were elucidated based on elemental analysis, spectral data, and alternative synthetic pathways, whenever possible. Some of benzimidazole derivatives were tested as corrosion inhibitors.     

Design,Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors

Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC₅₀ values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC₅₀ values of 14.0, 13.7 and 13.0 µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.     

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis,In Vitro and In Silico Studies

Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC₅₀ = 2.5 µM) than that of positive controls ursolic acid (IC₅₀ = 5.6 µM), claramine (IC₅₀ = 13.7 µM) and suramin (IC₅₀ = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.