吡嗪类碳酰肼化合物与CT-DNA相互作用及体外抑菌

以5-氯吡嗪-2-羧酸甲酯和水合肼为原料,经亲核取代和脱水缩合反应合成了3种新型吡嗪类碳酰肼化合物C13H14N6O(a)、C13H14N6O2(b)和C12H12N6O2(c)。采用元素分析与核磁共振氢谱对化合物a~c进行了表征,结果表明合成的产物即为目标化合物。通过溶剂挥发法培养得到了化合物a的单晶并利用X-射线单晶衍射测定化合物a的晶体结构为单斜晶系。根据紫外-可见光谱可知,化合物a~c均以插入模式与CT-DNA作用。利用微量热实验测定了化合物a~c与CT-DNA的相互作用,发现反应过程放热,热效应ΔH依次为-5.77×103、 -5.50×103和-5.96×103 kJ·moL-1,反应时间均小于40 min。通过分子对接模拟计算明确了化合物a和b与DNA的具体结合位点包括A链DC4和DG5以及B链DC4、 DG5和DA6,化合物c与DNA的具体结合位点包括A链DC4和DG5以及B链DC4和DG5。采用牛津杯法测定了化合物a~c对枯草芽孢杆菌、金黄色葡萄球菌、铜绿假单胞菌以及大肠杆菌四种细菌的抑菌活性,结果表明化合物a~c均对铜绿假单胞菌表现出优于阳性对照组四环素的抑菌活性。     

Synthesis of chalcone precursor via Cu(I) catalyzed 1,3-dipolar reaction of functionalized acetylene and pyrazole embedded dipole

A new class of functionalized pyrazole bearing 1,2,3-triazole has been synthesized via Cu(I) mediated 1,3-dipolar cycloaddition of pyrazole bearing azide with various aromatic/heteroaromatic bearing terminal dipolarophile (acetylene). Structures of the newly synthesized compounds were explicated by analytical and spectral analysis. All the newly synthesized compounds were evaluated for their in-vitro antibacterial and antioxidant activity. Among the synthesized compound, triazole bearing 2,5-thiazolidinone 5b (20 ± 0.70) and triazole bearing thiocarboamide 5e (19 ± 0.70) showed good antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, respectively. The newly synthesized compounds further tested for their ability to bleach DPPH radical using DPPH scavenging assay. Among the synthesized compounds 1,2,3-triazole bearing 2,5-thiazolidinone 5b (58.81%) exhibited good DPPH scavenging activity compared to the rest of the compounds. From the X-ray and Hirshfield analysis, it was observed that compound 3 , crystallizes in a triclinic crystal system with a P-1 space group. The major intercontacts present in these molecules are H…H (39.7%), C…H (23.9%), N…H (20.3%).     

In silico ADME predictions and in vitro antibacterial evaluation of 2-hydroxy benzothiazole-based 1,3,4-oxadiazole derivatives

In the present work, a library of fifteen 2-hydroxy benzothiazole-linked 1,3,4 -oxadiazole derivatives have been synthesized and confirmed using different analytical techniques. All of the synthesized compounds have been tested for antibacterial and in silico pharmacokinetic studies for the first time. From the ADME predictions, compound 4 showed the highest in silico absorption percentage (86.77%), while most of the compounds showed more than 70% absorption. All of the compounds comply with the Lipinski rule of 5, suggesting that the compounds possess good drug likeness properties upon administration. Furthermore, all of the compounds follow the Veber rule, indicating good bioavailability and good intestinal absorption. The antibacterial results exhibited excellent to moderate activity. Compounds 5 , 9 , 12 , 14 , 15 , 16 , and 17 were the most active compounds against the tested bacterial strains. Compound 14 showed comparable MIC 6.25 ±0.2 μg/disc to the standard drug amoxicillin against the tested Gram-positive bacterial strains. Compounds 5 , 14 , 17 exhibited MIC 12.5 ±0.8 μg/disc, which was comparable to the standard drug against E. faecalis . It can be concluded that the synthesized compound could be used as a lead molecule in the development of new antibacterial agents with high efficacy.     

Synthesis and antibacterial evaluation of nitrogen containing novel heterocyclic chalcones

Thirteen different novel heterocyclic chalcones were synthesized using cycloaddition and Claisen–Schmidt condensation reactions. These newly synthesized compounds were characterized by their spectral studies and structure of (E)-3-(4-methoxyphenyl)-1-(5-methyl-1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)prop-2-en-1-one (4h) was also evidenced by single crystal X-ray studies. These compounds were evaluated for antibacterial activities against seven bacterial strains in vitro. Compounds 4b and 4c containing 4-fluoro and 4-chloro groups have shown remarkable inhibition as showed by the standard drug ciprofloxacin against Escherichia coli and Staphylococcus aureus, respectively. Another compound 4k containing 3,4,5-trimethoxy group also showed similar activity against both these strains. Beside these three potential compounds 4b, 4c, 4k, one more compound 4g containing 4-methyl group showed equivalent inhibition as that of standard drug against E. coli. These categories of compounds are therefore good candidates for developing new effective antibacterial in future.     

哌啶并噻吩并嘧啶酮衍生物的合成、表征及生物活性

应用中间体碳二亚胺分别与伯胺、仲胺及醇在醇钠催化条件下合成9个未见报道的新型哌啶并噻吩并嘧啶酮衍生物.产物的结构经元素分析、1H NMR、MS及单晶X衍射检测得以确认.探讨了所有化合物的杀菌活性,结果表明部分化合物表现出较好的抑菌活性,其中化合物7b对黄瓜灰霉、水稻纹枯、小麦赤霉的抑制率分别为76.19%,68.83%和56.52%.     

N-(2-(腈基(4,6-二甲氧基嘧啶-2-基)甲基)苯基)酰胺类衍生物的合成及生物活性

以2-(2-硝基苯基)乙腈及4,6-二甲氧基-2-甲磺酰基嘧啶为起始原料,分别经缩合、还原及酰胺化反应合成了6个未见文献报道的N-(2-(腈基(4,6-二甲氧基嘧啶-2-基)甲基)苯基)酰胺类衍生物,其结构经1H NMR、MS和元素分析进行了确证。 在150 g/hm2的用量条件下,合成化合物未显示出除草活性。 在200 mg/L浓度下,部分化合物对黄瓜灰霉病及水稻纹枯病表现出一定的抑菌作用,其中化合物4d对水稻纹枯病的抑制率为72.33%。     

Design,Ultrasonic-assisted Synthesis and Evaluation In vitro Antimicrobial Activity of Bis-isoxazole Derivatives Bearing Chloro-pyridinyl Group

An ultrasonic-assisted synthesis of bis-isoxazole derivatives was developed. Eight 3-(6-chloropyridin-3-yl)-5-{[(3-aryli-soxazol-5-yl)methoxy]methyl}isoxazoles were synthesized by 1,3-dipolar cycloaddition reaction between substituted isoxazolyl alkyne compounds and 6-chloro-N-hydroxynicotinimidoyl chloride. The structures of the synthesized compounds were confirmed by HRMS, FTIR, ¹H and ¹³C NMR spectroscopy. Wherein, the antifungal and antibacterial activities of target compounds were tested. The synthesized compounds 6a and 6h exhibited better antifungal activity in comparison with the standard drug itraconazole. The minimum inhibitory concentrations(MICs) of both compound 6a and compound 6h were both 4 μg/mL against Candida albicans ATCC 10231.     

Novel 1,4-benzothiazine derivatives: synthesis,crystal structure,and anti-bacterial properties

In order to develop relatively small molecules as pharmacologically active molecules, novel 1,4-benzothiazine derivatives with triazole and oxazolidinone were synthesized. In this study, a series of 1,2,3-triazolylmethyl-1,4-benzothiazine derivatives were developed by exploiting a click chemistry reaction using a CuI-catalyzed Huisgen [3 + 2] cycloaddition. Starting from 2-(substituted)-3,4-dihydro-2H-1,4-benzothiazi-3-one, a number of 1,4-benzothiazine derivatives were also synthesized using different alkylating agents to give a 4-(substituted)-2-(substituted)-3,4-dihydro-2H-1,4-benzothiazi-3-one in good yields. The crystal and molecular structure of compound oxazolidin-2-one in basic benzothiazine was established by single-crystal X-ray diffraction. The newly synthesized products were subjected to in vitro biological evaluation. The result indicated that the compounds show convincing antibacterial activities against different microorganisms. All structures of the synthesized compounds were elucidated on the basis of spectral analyses and chemical reactions.     

Design,synthesis, antimicrobial activity and computational studies of novel azo linked substituted benzimidazole,benzoxazole and benzothiazole derivatives

Novel azo linked substituted benzimidazole, benzoxazole, and benzothiazole were synthesized by diazo coupling and characterized by ¹H NMR, elemental analysis, FTIR and UV–vis spectroscopy. The newly synthesized compounds were evaluated for invitro antibacterial activity against Staphylococcus aureus and Escherichia Coli strains by Resazurin microtiter assay method (REMA). The minimum inhibitory concentration (MIC in μg/mL) were used to express the antibacterial activities. The azo linked compounds exhibited good to moderate or high antibacterial activities in vitro. Computational studies were performed to correlate HOMO-LUMO gap with antibacterial activity. The comparative molecular docking studies revealed better insights into binding mechanisms.     

Synthesis, characterization, antibacterial and antifungal evaluation of novel monosaccharide esters

A novel series of 3-(2-furyl)acrylate monosaccharide esters Ia–f and menthyloxycarbonyl monosaccharide esters IIa–f were designed and synthesized. The chemical structures of the target compounds were confirmed by IR, 1H- and 13C-NMR and ESI-MS, and the target compounds were investigated for their in vitro antibacterial and antifungal activities. The antibacterial screening results showed that the 3-(2-furyl)acrylate monosaccharide ester derivatives Ia–f were either inactive or only weakly active against the three Gram-positive bacterial strains tested, whereas the menthyloxycarbonyl monosaccharide ester derivatives IIa–f exhibited higher levels of activity, with compound IIe being especially potent. The results of the antifungal screening revealed that compounds Ib, Ie, IIb and IIc displayed potent in vitro activities, whereas If and IIf showed promising activities against all of the microorganisms tested, with If exhibiting levels of activity deserving of further investigation.     

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis,Biological Activities,Molecular Modeling,ADME, and Molecular Dynamics Studies

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.     

Design,Synthesis and Insecticidal Activities of Novel 5-Alkoxyfuran-2(5H)-one Derivatives

A series of novel 5?alkoxyfuran-2(5H)-one derivatives was synthesized, and characterized by 1H NMR, 13C NMR and HRMS. Biological activities of all the title compounds were evaluated systematically. Preliminary bioassays indicated that most of the compounds exhibited moderate insecticidal activities against Aphis craccivora and Nilaparvata lugens at 100 mg/L. Compounds 4h and 4w exhibited 100% mortality rate against Aphis craccivora at 100 mg/L, and compound 4h exhibited good mortality rate against Aphis craccivora and Nilaparvata lugens (60% and 75%, respectively) even at 4 mg/L. The results demonstrated the impact of various chemical groups on insecticidal activities and provided a potential clue for further exploring novel high-effective broad-spectrum insecticides.     

Synthesis,antibacterial, and antiviral activities of novel penta-1,4-dien-3-one derivatives containing a benzotriazin-4(3<Emphasis Type="Italic">H</Emphasis>)-one moiety

A series of penta-1,4-dien-3-one containing a benzotriazin-4(3H)-one moiety were prepared and evaluated for their antibacterial and antiviral activities. Bioassays indicated that some compounds exhibited good antibacterial and antiviral activities. Among them, the EC₅₀ values of compound 6d against Xanthomonas axonopodis pv. citri and compound 6l against Ralstonia solanacearum were, respectively, 22.45 and 34.77 μg/mL, which were better than that of thiodiazole copper (51.35 and 87.26 μg/mL, respectively). Meanwhile, some title compounds were found to show remarkable antiviral activities against tobacco mosaic virus (TMV). These results indicated that penta-1,4-dien-3-one derivatives containing benzotriazin-4(3H)-one moiety could play significant roles in searching for novel agrochemicals.     

N-取代苯基-卤代邻羟基苄胺的合成、表征及抑菌活性

通过卤代水杨醛与取代芳胺缩合、NaBH4还原, 合成了15种N-取代苯基-卤代邻羟基苄胺化合物, 其中14种未见报道. 化合物的结构经IR, 1H NMR, MS与元素分析表征确证. 抑菌测试表明, 在质量浓度为0.05%时, 化合物对白色念珠菌的抑菌率高达100%, 具有强抑菌活性, 对金黄色葡萄球菌、大肠杆菌有一定的抑菌活性. 该类化合物对不同菌株的抑菌活性具有明显的选择性和特异性, 是一类极具潜力的抗真菌化合物. 构效分析表明, 胺基苯环上取代基的类型对化合物抑菌活性有重要影响, 引入F, Cl等卤原子, 能显著增强化合物的抑菌活性, 而引入NO2, OCH3等强吸、供电基团, 能显著降低其抑菌活性; 邻羟基苯环上引入卤原子的类型和数量对化合物抑菌活性有一定影响, 5-溴代化合物比5-氯代化合物、3,5-二溴代化合物对大肠杆菌的抑菌活性更高.     

Design,Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing Tetrahydrophthalimide Substructure

To develop novel sulfonylurea herbicides, a series of chlorsulfuron derivatives was designed and synthesized through introducing tetrahydrophthalimide substructure taken from protoporphyrinogen IX oxidase(PPO) inhibitors onto the critical 5-position of the classical benzene ring. The structures of title compounds were confirmed by infrared spectroscopy, ultraviolet spectroscopy, ¹H and ¹³C NMR spectrometry, mass spectrometry and elemental analysis. In addition, the crystal structure of compound II-5 was further determined by X-ray diffraction analysis. Bioassay results showed that individual compounds exhibited good herbicidal activities, especially compound II-8, which displayed 100% inhibition rate against Echinochloa crusgalli at 150 g/ha(1 ha=10⁴ m²) with the method of foliage spray in the pot experiment.     

PMBP缩氨基酚的合成、晶体结构及抑菌活性

利用1－苯基－3－甲基－4－苯甲酰基－5－吡唑啉酮（PMBP）与邻、间、对氨 基酚合成了三种PMBP缩氨基酚Schiff碱，并进行了结构表征。PMBP缩邻氨基酚的X 射线衍射分析测定结果表明，该缩合反应是通过质子转移形式，形成了烯胺酮式结 构。抑菌活性测定结果表明它们对革兰氏阳性金黄色葡萄球菌和革兰氏阴性大肠杆 菌有较强的抑制作用。     

N-苄氧/烷氧苯基-4,6-二取代嘧啶胺类化合物的合成、晶体结构及除草活性

以5种苄氧基/烷氧基苯胺为基础, 设计合成了系列新颖的N-苄氧/烷氧苯基-4,6-二取代嘧啶胺类化合物, 其结构经1H NMR、MS及元素分析确证, 其中化合物5r的单晶结构经X射线单晶衍射分析确证. 油菜平皿法和稗草小杯法测试除草活性结果表明, 4种苄氧基/烷氧基苯胺3a, 3b, 3d, 3e具有较好的除草活性, 在100 μg/mL浓度下对单子叶稗草生长抑制率可达到77.3%—88.5%. KARI活性测试结果表明, 化合物5a—5s有较弱的KARI抑制活性.     

Synthesis,biological evaluation,and docking study of a series of 1,4-disubstituted 1,2,3-triazole derivatives with an indole-triazole-peptide conjugate

A series of new compounds containing an indole-triazole - peptide conjugate were designed as potential agents possessing the dual anti-bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi-step synthesis involving the copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, ¹H and ¹³C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram-positive (Staphylococcus aureus) and three gram-negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar-well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔG_bind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b , 9k, and 9e showed low IC₅₀ values.     

Design,Synthesis, Antifungal Activities and SARs of (R)‐2‐Aryl‐4,5‐dihydrothiazole‐4‐carboxylic Acid Derivatives

Based on the structure of natural product 2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid, a series of novel (R)‐2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of compound 9b was determined by X‐ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidicola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 µg?mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.     

Synthesis and Antimicrobial Evaluation of Novel Polyfused Heterocycles‐Based Quinolone

Syntheses of some new heterocyclic compounds incorporating quinolone moieties were achieved via reaction of 4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 1 ) or 3‐bromo‐4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 2 ) with binucleophilic reagents. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR and mass spectra). The newly synthesized compounds were screened for their antibacterial activity against Gram‐positive bacteria (Bacillus thuringiensis) and Gram‐negative bacteria (Escherichia coli). The results showed clearly that compounds 1 and 3 are the more potent antibacterial agents against E. coli, compounds 4 , 5 , 6 and 8 , 9 , 10 , 11 , 12 , 13 exhibited moderate activities against E. coli strain, and compounds 7 and 11 exhibited weak activities compared with Gentamicin as a well known standard drug.