We report the synthesis of benzimidazole derivatives using zinc triflate as an efficient catalyst. One-pot synthesis of 2-substituted benzimidazole derivatives from o-phynelyenediamine and substituted aldehydes were d...We report the synthesis of benzimidazole derivatives using zinc triflate as an efficient catalyst. One-pot synthesis of 2-substituted benzimidazole derivatives from o-phynelyenediamine and substituted aldehydes were developed under zinc triflate in ethanol solvent at reflux temperature.展开更多
In order to discover the novel anti-tumor agents, a series of 2-[（pyridin-2-yl）methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR...In order to discover the novel anti-tumor agents, a series of 2-[（pyridin-2-yl）methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[（3,4-Dimethoxypyridin-2-yl）methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828（16）, b = 11.625（2）, c = 13.463（2） ？, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.展开更多
This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR...This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR) method. The molecules were optimized at the level DFT/B3LYP/6-31 + G (d, p), to obtain the molecular descriptors. We used three statistical learning tools namely, the linear multiple regression (LMR) method, the nonlinear regression (NLMR) and the artificial neural network (ANN) method. These methods allowed us to obtain three (3) quantitative models from the quantum descriptors that are, chemical potential (μ), polarizability (α), bond length l (C = N), and lipophilicity. These models showed good statistical performance. Among these, the ANN has a significantly better predictive ability R<sup>2</sup> = 0.9995;RMSE = 0.0149;F = 31879.0548. The external validation tests verify all the criteria of Tropsha et al. and Roy et al. Also, the internal validation tests show that the model has a very satisfactory internal predictive character and can be considered as robust. Moreover, the applicability range of this model determined from the levers shows that a prediction of the pMIC of the new benzimidazole derivatives is acceptable when its lever value is lower than 1.展开更多
Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today.Drug insensitivity and resistance are critical hurdles in cancer treatment;therefore,the development of ...Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today.Drug insensitivity and resistance are critical hurdles in cancer treatment;therefore,the development of new entities targeting malignant cells is considered a high priority.Targeted therapy is the cornerstone of precision medicine.The synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological properties.Benzimidazole has a heterocyclic pharmacophore,which is an essential scaffold in drug and pharmaceutical development.Multiple studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics,either through targeting specific molecules or non-gene-specific strategies.This review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure-activity relationship from conventional anticancer to precision healthcare and from bench to clinics.展开更多
In this paper,^(1)H NMR spectroscopy,isothermal titration calorimetry,X-ray crystallography and other characterization methods were used to investigate the interaction modes of tetramethyl cucurbit[6]uril(TMeQ[6])and ...In this paper,^(1)H NMR spectroscopy,isothermal titration calorimetry,X-ray crystallography and other characterization methods were used to investigate the interaction modes of tetramethyl cucurbit[6]uril(TMeQ[6])and three benzimidazole derivatives in an aqueous solution-solid state.The results showed that the aromatic ring moieties in the three derivatives all entered the cavity of TMeQ[6]and their substituents were located at the port of TMeQ[6],forming 1:1 host-guest inclusion complexes.The crystal structures showed that the aromatic part of the benzimidazole derivatives interacted with the cavity of TMeQ[6]via hydrogen bond interactions and the N atoms on the benzimidazole ring formed hydrogen bonds with the carbonyl oxygen of TMeQ[6].The ion-dipole interactions between[ZnCl_(4)]^(2-)and TMeQ[6]formed supramolecular self-assembly entities.展开更多
Sym-bis（benzimidazole）-2,2＇-ethylene cations act as a new axle template for threading cucurbit[6]uril derivatives on,forming[2]pseudorotaxane and[3]pseudorotaxane.These new complexes have been studied using 1 H NMR...Sym-bis（benzimidazole）-2,2＇-ethylene cations act as a new axle template for threading cucurbit[6]uril derivatives on,forming[2]pseudorotaxane and[3]pseudorotaxane.These new complexes have been studied using 1 H NMR,UV-vis absorption spectroscopy and X-ray analysis.Changes in the 1 H NMR spectra indicate that the two types of pseudorotaxane can be formed by varying the host concentration. UV-vis absorption titration experiments at different pH values demonstrate that interesting pK_a shifts of the bis-benzimidazole derivatives can be induced by the host-guest complexation.The associated constants were calculated to be 2.81×10^4 L/mol and 9.06×10^6 L/mol for the[2]pseudorotaxanes and ｜3]pseudorotaxanes,respectively.Furthermore,X-ray diffraction studies of the solid state structures provide unequivocal proof of the host concentration dependent pseudorotaxane,which is strongly in line with the evidences in solution.展开更多
A series of benzimidazole derivatives have been designed, synthesized and evaluated for H1 antihistamine activity. Six compounds have showed potent antihistamine H1 activity. The primary SAR analysis indicated that be...A series of benzimidazole derivatives have been designed, synthesized and evaluated for H1 antihistamine activity. Six compounds have showed potent antihistamine H1 activity. The primary SAR analysis indicated that benzyl or benzylidinyl substituted on the exo-nitrogen atom and C2 of the benzimidazole were significant. Further experiments indicated that compound 17d displayed excellent activity to reduce mast cell degranulation, moderate anti-PAF activity and decreased potency on hERG compared to astennizole. Hence compound 17d could serve as anti-allergic agent for further development.展开更多
Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-r...Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-racterized by 1H NMR, 13C NMR and high resolution mass spectra（HRMS） and preliminarily screened for inhibitoryactivity against thrombin, among which three compounds（5a, 5c and 5e） were evaluated in vitro. The results showedthat compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demon-strated that these compoands may act as candidates for further studies on thrombin inhibitors.展开更多
The four fluorescence coumarine derivatives were synthesized by reaction of bromo alkene and 7-hydroxyl coumarin.Their structures were characterized by IR,1HNMR,13CNMR and MS.UV-visible spectra and fluorescence spectr...The four fluorescence coumarine derivatives were synthesized by reaction of bromo alkene and 7-hydroxyl coumarin.Their structures were characterized by IR,1HNMR,13CNMR and MS.UV-visible spectra and fluorescence spectra showed that they have strong fluorescence.It was also showed that these derivatives exhibit excellent stability through the cyclic voltammograms.展开更多
文摘We report the synthesis of benzimidazole derivatives using zinc triflate as an efficient catalyst. One-pot synthesis of 2-substituted benzimidazole derivatives from o-phynelyenediamine and substituted aldehydes were developed under zinc triflate in ethanol solvent at reflux temperature.
基金supported by the National Natural Science Foundation of China(No.21342006)the Program for Innovative Research Team of the Ministry of Education of China(No.IRT_14R36)
文摘In order to discover the novel anti-tumor agents, a series of 2-[（pyridin-2-yl）methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[（3,4-Dimethoxypyridin-2-yl）methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828（16）, b = 11.625（2）, c = 13.463（2） ？, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.
文摘This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR) method. The molecules were optimized at the level DFT/B3LYP/6-31 + G (d, p), to obtain the molecular descriptors. We used three statistical learning tools namely, the linear multiple regression (LMR) method, the nonlinear regression (NLMR) and the artificial neural network (ANN) method. These methods allowed us to obtain three (3) quantitative models from the quantum descriptors that are, chemical potential (μ), polarizability (α), bond length l (C = N), and lipophilicity. These models showed good statistical performance. Among these, the ANN has a significantly better predictive ability R<sup>2</sup> = 0.9995;RMSE = 0.0149;F = 31879.0548. The external validation tests verify all the criteria of Tropsha et al. and Roy et al. Also, the internal validation tests show that the model has a very satisfactory internal predictive character and can be considered as robust. Moreover, the applicability range of this model determined from the levers shows that a prediction of the pMIC of the new benzimidazole derivatives is acceptable when its lever value is lower than 1.
基金the Ministry of Higher Education Malaysia for the Fundamental Research Grant Scheme with the Project Code:FRGS/1/2021/SKK06/USM/02/7 for supporting this work。
文摘Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today.Drug insensitivity and resistance are critical hurdles in cancer treatment;therefore,the development of new entities targeting malignant cells is considered a high priority.Targeted therapy is the cornerstone of precision medicine.The synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological properties.Benzimidazole has a heterocyclic pharmacophore,which is an essential scaffold in drug and pharmaceutical development.Multiple studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics,either through targeting specific molecules or non-gene-specific strategies.This review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure-activity relationship from conventional anticancer to precision healthcare and from bench to clinics.
基金supported by the National Natural Science Foundation of China(No.22161010)。
文摘In this paper,^(1)H NMR spectroscopy,isothermal titration calorimetry,X-ray crystallography and other characterization methods were used to investigate the interaction modes of tetramethyl cucurbit[6]uril(TMeQ[6])and three benzimidazole derivatives in an aqueous solution-solid state.The results showed that the aromatic ring moieties in the three derivatives all entered the cavity of TMeQ[6]and their substituents were located at the port of TMeQ[6],forming 1:1 host-guest inclusion complexes.The crystal structures showed that the aromatic part of the benzimidazole derivatives interacted with the cavity of TMeQ[6]via hydrogen bond interactions and the N atoms on the benzimidazole ring formed hydrogen bonds with the carbonyl oxygen of TMeQ[6].The ion-dipole interactions between[ZnCl_(4)]^(2-)and TMeQ[6]formed supramolecular self-assembly entities.
基金supported by the National Natural Science Foundation of China(No,21272045)the Natural Science Foundation of Guizhou Province and Guizhou Universitythe "Chun-Hui" Funds of the Chinese Ministry of Education are gratefully acknowledged
文摘Sym-bis（benzimidazole）-2,2＇-ethylene cations act as a new axle template for threading cucurbit[6]uril derivatives on,forming[2]pseudorotaxane and[3]pseudorotaxane.These new complexes have been studied using 1 H NMR,UV-vis absorption spectroscopy and X-ray analysis.Changes in the 1 H NMR spectra indicate that the two types of pseudorotaxane can be formed by varying the host concentration. UV-vis absorption titration experiments at different pH values demonstrate that interesting pK_a shifts of the bis-benzimidazole derivatives can be induced by the host-guest complexation.The associated constants were calculated to be 2.81×10^4 L/mol and 9.06×10^6 L/mol for the[2]pseudorotaxanes and ｜3]pseudorotaxanes,respectively.Furthermore,X-ray diffraction studies of the solid state structures provide unequivocal proof of the host concentration dependent pseudorotaxane,which is strongly in line with the evidences in solution.
基金supported by National Major Scientific and Technological Special Project(No.2009ZX09301 -003)
文摘A series of benzimidazole derivatives have been designed, synthesized and evaluated for H1 antihistamine activity. Six compounds have showed potent antihistamine H1 activity. The primary SAR analysis indicated that benzyl or benzylidinyl substituted on the exo-nitrogen atom and C2 of the benzimidazole were significant. Further experiments indicated that compound 17d displayed excellent activity to reduce mast cell degranulation, moderate anti-PAF activity and decreased potency on hERG compared to astennizole. Hence compound 17d could serve as anti-allergic agent for further development.
文摘Some 1,2,5-trisubstituted benzimidazole fluorinated derivatives were designed and screened by moleculardocking. Five compounds which obtained high scores were selected to synthesize. All the target products were cha-racterized by 1H NMR, 13C NMR and high resolution mass spectra（HRMS） and preliminarily screened for inhibitoryactivity against thrombin, among which three compounds（5a, 5c and 5e） were evaluated in vitro. The results showedthat compounds 5a, 5c and 5e exhibited better anticoagulant activity than argatroban. Docking simulations demon-strated that these compoands may act as candidates for further studies on thrombin inhibitors.
文摘The four fluorescence coumarine derivatives were synthesized by reaction of bromo alkene and 7-hydroxyl coumarin.Their structures were characterized by IR,1HNMR,13CNMR and MS.UV-visible spectra and fluorescence spectra showed that they have strong fluorescence.It was also showed that these derivatives exhibit excellent stability through the cyclic voltammograms.
