Synthesis,antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB) with MIC 12.5?μg/mL. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.     

取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

为了寻求新的含吡唑双杂环先导化合物. 用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物. 化合物结构用IR, ¹H NMR, MS和元素分析进行了表征. 并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构. 晶体为单斜晶系, P2₁/n (#14)空间群, a＝1.52175(3) nm, b＝0.52970(1) nm, c＝1.58185(3) nm, β＝104.893(4), V＝1.2323(4) nm³, Z＝4, D_c＝1.45 g/cm³, F(000)＝560.00, R₁＝0.064, wR₂＝0.193. 初步生物活性实验结果表明, 在25 mg/L浓度下, 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c), 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%. 在500 mg/L浓度下, 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d), 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cinc-ticeps)的抑制活性达到53.37%.     

Design,synthesis, and anticancer activity evaluation of novel aziridine-1,2,3-triazole hybrid derivatives

Some new 1-aryl-4-[(aziridine-1-yl)diaryl-methyl]-5-methyl-1H-1,2,3-triazole derivatives 7j–s were synthesized by the one-pot reaction of diaryl-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)methanol compounds 6j–s formed from 1-aryl-5-methyl-1H-1,2,3-triazole-4-carboxylic acid derivatives. The new compounds 7j–s and 6j–s are investigated by ¹H and ¹³C NMR, MS, and IR. The anticancer activity of the synthesis target compounds was evaluated against human leukemia (HL-60) cells and human hepatoma G2 cells. Some of the compounds were highly efficient. The ¹H-NMR signals of the aziridine-ring cis-H/trans-H protons were found to be two group peaks at 1.800–1.884 and 1.183–1.327?ppm.     

新型手性<i>β</i>-烷氨基-<i>γ</i>-(<i>l</i>-孟氧基)丁内酯的合成

脂肪族伯胺作为亲核试剂与手性合成子5(R)-(l-孟氧基)-2(5H)-呋喃酮(4)发生不对称Michael加成反应, 得到一系列新的手性β-烷氨基-γ-(l-孟氧基)丁内酯类化合物6(产率34～81%, de≥98%). 通过IR, ¹H NMR, ¹³C NMR, MS, 元素分析及单晶X射线衍射分析, 确认了它们的化学结构、立体化学和绝对构型. 此结果为某些具有生物活性化合物及复杂分子的合成提供了新的途径.     

A new lactam alkaloid from Portulaca oleracea L. and its cytotoxity

A new lactam alkaloid named oleraciamide D (1), indentified as (5R)-4-(3-methoxy-4-hydroxyphenyl)-5-(4-hydroxyphenyl)-5,6-dihydropyridin-2(1H)-one, together with five known compounds, indole-3-aldehyde (2), portulacatone (3), N-trans-feruloyloctopamine (4), N-trans-feruloyl-3′-O-methyldopamine (5) and N-trans-feruloyltyramine (6) were isolated from Potulaca oleracea L. Among them, indole-3-aldehyde (2) was isolated from the medicine for the first time. The structure of the new alkaloid was elucidated via UHPLC-ESI-Q-TOF/MS, 1D NMR and 2D NMR. The five known compounds were established by comparing the ¹H-NMR and ¹³C NMR with the reported literature. Oleraciamide D (1) showed cytotoxicity against SH-SY5Y cells when concentration at 50 uM by CCK-8 method.     

Synthesis,characterization, and investigations of antimicrobial activity of 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4(5H)-dione

Chalcone-like compounds 3a–l, 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one, were synthesized from the addition of different benzaldehyde derivatives (2a–l) to 1,2,3,4-tetrahydro-1-napthalone (1) in basic medium. Mn(OAc)₃-mediated addition of dimedone (4) to chalcone-like compounds gave the spirobenzofuran derivatives (5a-l), 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4 (5H)-dione, in good yields. The structures of synthesized compounds 5a–l were elucidated on basis of spectral data (NMR, IR) and elemental analysis. In addition, their antibacterial activities were screened against some human pathogenic microorganisms.     

New angular oxazole-fused coumarin derivatives: synthesis and biological activities

Twelve angular oxazole-fused coumarin derivatives were designed, synthesised and characterised by ¹H NMR, ¹³C NMR and HRMS. The structure of compound 4a was further confirmed by X-ray single-crystal diffraction. The bioassay experiment results indicated that compounds 4f and 4l have high antifungal activity on the mycelium growth of 4 plant disease fungi. Especially, compound 4l has a stronger antifungal activity compare to the commercial fungicide, Carbendazim. The herbicidal activity experiment showed that 4a and 4b can significantly inhibit the taproot and caulis development of Chenopodium album seedling and have better activities than the commercial herbicide, Acetochlor.     

氢化喹啉及其芳(杂)环稠合衍生物的合成

通过环己二酮与β-二腈基苯乙烯的Michael加成得到2-氨基-3-氰基-4-芳基-5-氧代-1,4,5,6,7,8-六氢喹啉(1); 4-苯基六氢喹啉(1a)与环己二酮发生胺的加成缩合反应生成2-N-(3-氧代-1-环己烯基)氨基-3-氰基-4-苯基-5-氧代-1,4,5,6,7,8-六氢喹啉(2), 在碱性和氯化亚铜催化下进一步环合成4-苯基-5-氨基-二-(2-氧代环己烷)并[b,g]-1,3-二氢萘啶(3). 芳醛、α-萘胺和环己二酮在乙醇中共回流, 则一锅法完成9-芳基-5,6,7,8,9,10-六氢苯并[c]吖啶酮(4)的合成. 对合成中所涉及的化学反应机理进行了尝试性的讨论. 新化合物1a～4c均经IR, ¹H NMR 及元素分析证明其结构.     

Synthesis and Structure of Novel 1-Aryl-4,4,4-trichloro-1,3-butanediones

Novel 1-aryl-4,4,4-trichloro-1,3-butanediones in good yields (80–97%) were synthesized in one pot through acetal acylation with trichloroacetyl chloride followed by acid hydrolysis. Structures of all compounds were elucidated by elemental analysis, mass spectrometry, and ¹H/¹³C nuclear magnetic resonance (NMR) measurements. The ¹H/¹³C NMR data showed that trichloromethyl-β-diketones 2a–k in solution are predominantly ketoenol. However, the spectroscopic data from 4,4,4-trichloro-2-methyl-1-phenyl-1,3-butabedione (2l) with methyl substituent between carbonyls showed a bias toward the diketo form in solution. X-ray diffraction of monocrystals from 2g and 2i showed that these compounds are cis-ketoenol tautomers.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communcations® to view the free supplemental file.     

NaF-catalyzed efficient one-pot synthesis of dihydropyrano[2,3-c]pyrazoles under ultrasonic irradiation via MCR approach

Sodium fluoride was identified as an efficient catalyst for the preparation of series of dihydropyrano [2,3-c]pyrazoles (4a–l) by the three-component condensation of 3-Methyl-1-phenyl-2-pyrazoline-5-one (1), aromatic aldehydes (2) and malononitrile (3) in aqueous methanol at ambient temperature under ultrasonication. The cost and efficacy of the catalyst, mild reaction conditions, simple workup procedure, less reaction time and higher yields of the product with analytical purity keeping this protocol superior to the previously reported ones. Structures of all the compounds were in agreement with their spectroscopic data (¹H NMR, ¹³C NMR) and elemental (CHN) analyses.     

The One Step Synthesis of 2-(2-Bromo-5- methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]- 1,2,4-triazol-6-(5H)-ones and the Evaluation of the Anticonvulsant Activity

A smooth one-step synthesis of 2-(2-bromo-5-methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]-1,2,4-triazol-6-(5H)-ones (4a–n) is described. The newly prepared compounds are characterized by analytical and IR, ¹ H NMR, ¹³ C NMR, and FABMS spectral analysis. A few compounds are screened for anticonvulsant activity. Compounds 4i and 4n exhibit promising anticonvulsant activity and are recommended for further studies.     

微波辐射下合成5-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-3-(苯基/p-取代苯基)-2H-1',2',4'-三唑[3,4-b]-1

分别采用微波辐射法和加热回流的常规方法, 将1-氨基-2-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-5-巯基-1,3,4-三唑与α-溴代芳基乙酮3a～3e反应, 合成了一系列未见文献报道的1,2,4-三唑[3,4-b]-1',3',4'-噻二嗪类化合物4a～4e 和5a～5e. 微波辐射法具有反应时间短、产率高、副反应少等优点. 标题化合物经元素分析, IR, ¹H NMR, MS确证结构.     

异噁唑基取代的1,2,4-噁二唑啉和吡唑啉类化合物的合成

通过3-乙酰基-5-羟甲基异噁唑衍生的Schiff碱2与由醛肟原位生成的腈氧化物的1,3-偶极环加成反应, “一锅法”制备了5-甲基-5-[5-(叔丁基二甲基硅氧基甲基)-3-异噁唑基]-3-芳基-4-(4-甲氧基苯基)-4,5二氢-1,2,4-噁二唑类化合物4a～4e; 同时由3-乙酰基-5-羟甲基异噁唑衍生的α,β-不饱和酮(5)与取代苯肼的环化反应制备了5-(叔丁基二甲基硅氧基甲基)-3-[(1,5-二芳基)-3-(4,5-二氢吡唑基)]-异噁唑类化合物6a～6i. 所有新化合物的结构经核磁共振谱氢谱和碳谱、质谱、红外光谱以及高分辨质谱等进行了确证.     

Synthesis and Structure of a Novel Alkynyl-Containing Disulfide Compound as Cathode Materials for Secondary Lithium Batteries

A novel alkynyl-containing disulfide compound, 5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracen (TMSEDTTA), was synthesized. The structures of the target compound and the intermediates have been identified by ¹H NMR, ¹³C NMR, mass spectrometry, Fourier-transform infrared, Raman spectra, x-ray photoelectron spectroscopy, and elemental analysis. In addition, the structure of (Z)-(1,2-dibromo-2-(2,3,5,6-tetrakis(bromomethyl)phenyl)vinyl)trimethylsilane (5) was determined by single x-ray analysis.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

1-(嘧啶基-4)-3-(2,6-二氟苯甲酰基)脲衍生物的合成与生物活性

为了寻找高效、低毒、低残留的环境友好杀虫剂, 设计并合成了12个新的1-(嘧啶基-4)-3-(2,6-二氟苯甲酰基)脲衍生物6a～6l, 其结构经IR, ¹H NMR, LC/MS和元素分析确证. 初步生物活性测试结果表明, 部分化合物具有明显的杀虫活性, 如6g在100 mg/L浓度下, 对粘虫(Mythimna sepatara)具有100%的杀虫活性.     

Synthesis of novel 1,2,3-thiadizoles and 1,2,3-selenadiazoles as new antimicrobial agents

Abstract

A series of novel 1,2,3-thiadiazoles and 1,2,3-selenadiazoles having a long alkyl chain were synthesized by reacting semicarbazones with SOCl₂ and SeO₂, respectively. The structures of the target compounds 5–12 were confirmed by spectroscopy (IR, ¹H NMR, ¹³C NMR, and MS) and elemental analysis. Their antibacterial and antifungal activities were evaluated against six bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus) and three fungi (Candida albicans, Candida parapsilosis, Candida tropicalis). The results of bioassays indicated that the compounds 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7), 4-Methyl-5-tetradecyl-[1-3]selenadiazole (8) and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]thiadiazole (11) displayed moderate antibacterial activity against S. Epidermidis. On the other hand, according to antifungal screening results, compounds 5-Dodecyl-4-phenyl-[1-3]selenadiazole (5), 4-p-Tolyl-5-undecyl-[1-3]selenadiazole (6), and 5-Dodecyl-4-(4-methoxy-phenyl)-[1-3]selenadiazole (7) exhibited significant antifungal activities studied yeast strains.     

Diorganotin Complexes with N(4)-Phenylthiosemicarbazones: Synthesis,Spectroscopic Characterization,and Antibacterial Activity

Abstract

The organotin(IV) complexes, SnPh₂L^a (1), SnMe₂L^a (2), SnBu₂L^a (3), SnPh₂L^b (4), SnMe₂L^b (5), SnPh₂L^c (6), SnMe₂L^c (7), and SnBu₂L^c (8) were obtained by reaction of SnR ₂Cl₂ (R = Ph, Me, and Bu) with 1-(5-bromo-2-hydroxybenzylidene)-4-phenylthiosemicarbazide (H₂L^a), 1-((2-hydroxynaphthalen-1-yl)methylene)-4-phenylthiosemicarbazide (H₂L^b), and 1-(2-hydroxy-3-methoxybenzylidene)-4-phenylthiosemicarbazide (H₂L^c). The synthesized complexes have been investigated by elemental analysis, IR, ¹H NMR, and ¹¹⁹Sn NMR spectroscopy. The data show that the thiosemicarbazone acts as a tridentate dianionic ligand and coordinates via the thiol group, imine nitrogen, and phenolic oxygen. The coordination number of tin is 5. The in vitro antibacterial activities of the ligands and their complexes have been evaluated against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and compared with the standard antibacterial drugs.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the following free supplemental files: Additional figures and tables]     

Novel Triphenylamine Appended 1,3-Alternate-Calix[4]arenes: Synthesis and Characterization

In the present study, two novel calix[4]arene receptors containing triphenylamine units in 1,3-alternate conformation have been synthesized and characterized in detail. First, the 25,27-dipropoxy-26,28-bis[(3-aminopropyl)oxy]-calix[4]arene 4 and 25,26,27,28-tetra[(3-aminopropyl)oxy]-calix[4]arene 7 were prepared by using convenient reagents. Then, these amino derivatives of calix[4]arene were converted to Schiff base derivatives appended to triphenylamine of calix[4]arene (5 and 8) using 4-formyltriphenylamine via condensation. The 1,3-alternate conformation of the synthesized calix[4]arenes was determined by ¹H and ¹³C NMR analyses. Also, their structures have been characterized by using ¹H and ¹³C NMR, infrared, and elemental analyses.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.