Synthesis, antibacterial and antifungal activities of 3-aryl-5-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbothioamide derivatives

A new series of 3-aryl-5-(pyridin-3-yl)-1-thiocarbamoyl-2-pyrazoline derivatives (4a-j) were prepared by the reaction of azachalcons 3a-j with thiosemicarbazide in ethanolic sodium hydroxide. The structure of synthesized compounds were confirmed by ¹H NMR and Mass spectral data. Their antibacterial activities against Escherichia coli (CTP 7624), Staphylococcus aureus (ATCC 6538), Staphylococcus epidermidis (ATCC 12229), Pseudomonas aeruginosa (ATCC 9027), Bacillus subtilis (ATCC 1156) and Micrococcus luteus (ATCC 9341) were investigated. Antifungal activity of compounds against Candida albicans and Candida globrata were found to be inactive. Compounds 4a-j were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H ₃₇ Rv (ATCC 27294) in BACTEC 12B using a broth microdilution assay and Microplate Alamar Blue Assay (MABA). The preliminary results showed that compounds 4e, 4d and 4g had 87%, 93% and 92% inhibitory effect respectively.     

A green protocol for one pot synthesis of benzosuberone tethered thiadiazolopyrimidine-6-carboxylates using PEG-400 as potent anti-proliferative agents

A new concise and facile method was explored to synthesize a collection of new benzosuberone based thiadiazolo [3,2-a] pyrimidine-6-carboxylates using polyethylene glycol (PEG), which could be regarded as the derivatives of the hybrid scaffolds of bioactive natural benzosuberone and heterocyclic thiadiazolo[3,2-a]pyrimidine. The structures of the synthesized compounds were characterized by ¹H, ¹³C NMR, MS and IR; and their anti-proliferative activity was evaluated against four human cancer cell lines; A549, SKNSH, HeLa and MCF-7. Among the tested compounds, compound 8k showed the most prominent activity against all the cell lines and these results may lay the foundation for further design of novel anti-proliferative agents.     

Synthesis and antimicrobial screening of novel 9-{2-[(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1<Emphasis Type="Italic">H</Emphasis>-xanthene-1,8(2<Emphasis Type="Italic">H</Emphasis>)-dione derivatives

A series of novel 9-{2-[(1H-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione derivatives were synthesized by a click chemistry approach. The structures of all the newly synthesized compounds were characterized by IR, MASS, ¹H and ¹³C NMR spectral data. The final analogues showed good to excellent antibacterial and antifungal activities in an agar well diffusion assay. Compounds 6i and 6f were the most active against all the test bacterial and fungal strains.     

A convenient, rapid and eco-friendly synthesis of isoxazoline heterocyclic moiety containing bridge at 2°-amine as potential pharmacological agent

2-Amino-4-(coumarin-3-yl)-thiazole (1) reacted with acetyl chloride gives compound (2) which on further refluxed with various aromatic aldehydes gives compound (3a-j). Thus obtained (3a-j) on further condensed with NH₄OH.HCl using NaOH as a catalyst afforded isoxazoles (4a-j). All the synthesized compounds characterized on the basis of the IR, ¹H NMR, ¹³C NMR and elemental analysis. All the compounds have been screened for antibacterial activity against bacteria (Gram + ve) & (Gram ? ve) and antifungal activity.     

Synthesis,antioxidant activity,and α-glucosidase enzyme inhibition of α-aminophosphonate derivatives bearing piperazine-1,2,3-triazole moiety

A novel series of piperazine-1,2,3-triazole bearing dimethyl(((2-(4-((1H-1,2,3-triazole-4-yl)methyl)piperazin-1-yl)ethylamino)(2-hydroxyaryl)methyl)phosphonate derivatives have been prepared via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) (Click Reaction) and Schiff base reactions. The synthesized compounds were confirmed by spectral characterization (¹H, ¹³C and ³¹P NMR, and mass). The title compounds were evaluated for in vitro alpha glucosidase enzyme inhibition and in vitro antioxidant activity using DPPH and H₂O₂ methods.     

Ultrasound-assisted,one-pot,three-component synthesis and antibacterial activities of novel indole derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole moieties

Thirteen novel indole derivatives were efficiently synthesized through ultrasound irradiation by using 4-amino-5-(1H-indol-3-yl)-4H-[1,2,4]triazole-3-thiol (8) and 2-mercapto-5-substituted-1,3,4-oxadiazoles (5a–m). Compared with conventional and microwave methods, yields increased to 82–93%, and reaction times decreased to 15–35 min. The structures of these novel compounds were characterized by spectral data and elemental analysis. Two out of the synthesized compounds (10f and 10l) exhibited excellent activity against Staphylococcus aureus and Escherichia coli, and thus warrant further research.     

Synthesis and antimicrobial screening of 1,3,4-oxadiazole and clubbed thiophene derivatives

In the present study, a novel series of 2-{5-[4-(1-aza-2-(2-thienyl)vinyl)phenyl](1,3,4-oxadiazol-2-ylthio)}-N-arylacetamides (IV)_1–12 were synthesized and tested for their antimicrobial activity. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus. The chemical structures of newly synthesized compounds were elicited by IR, ¹H NMR, ¹³C NMR and mass spectral data. The synthesized bio-active compounds exhibited excellent to moderate antimicrobial activity. Compounds (IV)₅, (IV)₆ and (IV)₇ possess excellent antibacterial activity whereas compounds (IV)₆, (IV)₉ and (IV)₁₁ possess excellent antifungal activity.     

Green synthesis and antibacterial evaluation of some new 1-aryl-3-(1-aryl-1<Emphasis Type="Italic">H</Emphasis>-[1,2,3]triazol-4-yl)-propenones

A new series of 1-aryl-3-(1-aryl-1H-[1,2,3]triazol-4-yl)propenones (6a–6j) was synthesized by condensation of substituted acetophenones (5a–5c) with substituted 1-aryl-1H-[1,2,3]triazole-4-carbaldehydes (4a–4d) in the presence of potassium hydroxide under conditions of grinding and microwave irradiation. All the newly synthesized compounds were characterized by the IR, NMR, and mass spectroscopic analyses and their antibacterial activity against gram-positive and gram-negative bacterial strains was evaluated. Among the compounds synthesized, better activity was exhibited by 6a, 6c, 6f, 6g, and 6i.     

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.     

Novel thiosemicarbazone derivatives containing benzimidazole moiety: Green synthesis and anti-malarial activity

A series of (E)-2-[5-chloro-1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (7a–7t) and (E)-2-[1-(1H-benzo[d]imidazol-2-yl)ethylidene] N-(substituted) hydrazine carbothioamide (8a–8t) were prepared via the synthesis of 1-(substituted-1H-benzimidazol-2-yl) ethanol (3a–3b) which was synthesized by the condensation of substituted o-phenylenediamine (2a–2b) with dl-lactic acid (1) followed by oxidation with sodium hypochlorite in mild acidic condition to form the corresponding ketones 4a–4b. Final compounds were formed by condensation of 4a–4b with different thiosemicarbazides 6a–6t. A total of 40 compounds were synthesized and characterized by FT-IR, ¹H NMR, ¹³C NMR, Mass spectral technique and elemental analysis, in addition they were evaluated for anti-malarial properties. Among the compounds tested 7o, 7p, 7q, 7r, 7s, 8e and 8h exhibited good antimalarial activity in vitro.     

Design,synthesis and biological evaluation of novel isoniazid hybrids

We herein report the design and synthesis of novel isoniazid derivatives. Isoniazid derived Schiff bases (3 a-d) were subjected to cyclization with acetic anhydride and sulphuric acid to yield the 5′-substituted-3′-acetyl-5-(pyridin-4-yl)-3H-spiro[indole-3, 2-[1′, 3′, 4’]oxadiazol]-2′-yl acetates (4 a-d) and 8′-substituted-3’-(pyridin-4-yl)[1′,3′,4’]oxadiazino [6,5-b]indoles (5 a-d) respectively. The advantages of spectral methods were used for the confirmation of the structure of all the newly synthesized hybrid molecules. Further, these compounds were evaluated for their antibacterial activity against B. Subtilis, S. aureus, E. coli & S. typhi, antifungal activity against C. albicans, C. oxysporum, A. Flavus & A. niger, and antimycobacterial activity against M. tuberculosis. Amongst, the compounds 4b, 4c and 5c showed excellent inhibitory activity against tested microorganisms. Also, the DNA cleavage activity of selected compounds was carried out by the AGE method.     

Synthesis,characterization, and antimicrobial activity of novel (<Emphasis Type="Italic">E</Emphasis>)-1-(aryl)-3-{3, 5-dimethoxy-4-[(1-(aryl)-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]phenyl}prop-2-en-1-ones

The new chalcone derivatives containing the 1,2,3-triazole ring system, namely, (E)-1-(aryl)-3-{3,5-dimethoxy-4-[(1-(aryl)-1H-1,2,3-triazol-4-yl)methoxy]phenyl}prop-2-en-1-ones, were synthesized in 65–88% yield by the “click chemistry” reactions of substituted acetophenones, 4-hydroxy-3,5-dimethoxy-benzaldehyde, and different substituted azides. The structure of the compounds was determined by the FT-IR, ¹H NMR, ¹³C NMR, and mass spectroscopic analyses. Compounds 6a–6l were screened for in vitro antimicrobial activity by the agar disc diffusion method.     

Design, synthesis and antiproliferative activities of novel 5H-pyridazino[4,5-b]indoles

A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds.The structures were confirmed by ~1H NMR and MS.Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro.Three of compounds (1e,1g,and 1h) exhibited potent antiproliferative activities,especially compound 1h (with IC_(50) values of 5.2μmol/L and 1.9μmol/L against Bel-7402 and HT-1080,respectively).The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.     

Synthesis of new 1,2,3-triazole linked benzimidazolidinone: Single crystal X-ray structure,biological activities evaluation and molecular docking studies

A novel series of 1,2,3-triazole-benzimidazolidinone hybrid derivatives were designed and synthesized via click reaction, between various aryl azide and a terminal alkyne bearing a benzimidazolidinone moiety. All newly synthesized compounds, were efficiently characterized using ¹H NMR, ¹³C NMR and HRMS. Furthermore, the structure of one precursor 5b was supported by single crystal X-ray diffraction. All synthesized derivatives have been evaluated for their antimicrobial and anti-inflammatory activities. Biological activity tests exhibited that the target structures demonstrate that compounds 5a, 5b and 5f have a high antibacterial activity especially derivative 5b. Besides, the in vitro antifungal results revealed that the strongest inhibition recorded to compound 5b in comparison to other products against A. brasiliensis, A. fumigatus and C. albicans. Biological activity evaluation indicated that the synthesized compounds possess moderate anti-inflammatory effects. The most effective compound in terms of efficacy and potency was 5a. Molecular docking simulation was used to investigate the most active compounds' probable binding mechanisms in order to provide a plausible explanation for their biological activity.     

2-Alkyl-4-amino-5-(tert-butyl-NNO-azoxy)-2H-1,2,3-triazole 1-oxides: synthesis and reduction

A new approach to the synthesis of 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazole 1-oxides 1 was developed. Compounds 1 were obtained by reactions of 3-amino-4-(tert-butyl-NNO-azoxy)furoxan with aliphatic amines RNH₂ (R = Me, Et, Prⁱ, Bu, and Bu^t). 4-Amino-5-(tert-butyl-NNO-azoxy)-2-tert-butyl-2H-1,2,3-triazole 1-oxide was transformed under the action of acids into 4-amino-5-(tert-butyl-NNO-azoxy)-1-hydroxy-1H-1,2,3-triazole. Methylation of the latter with diazomethane mainly involves the O atom of the triazole oxide ring. Reduction of compounds 1 gave 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazoles and 4-amino-5-(tert-butyldiazenyl)-2-R-2H-1,2,3-triazoles (R = Me, Prⁱ, and Bu^t). The structures of the compounds obtained were confirmed by ¹H, ¹³C, and ¹⁴N NMR spectroscopy.     

Tyrosol 1,2,3-triazole analogues as new acetylcholinesterase (AChE) inhibitors

The present work proposed the preparation of triazolic analogues of tyrosol, a biophenol found in olive oil and whose wide range of bioactivities has been the target of many studies. We obtained fifteen novel tyrosol derivatives and the compounds of the series were later evaluated as acetylcholinesterase (AChE) inhibitors. The study of AChE inhibition is important for the development of new drugs and pesticides, and especially the research for managing Alzheimer's disease. The most active compound, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (30), showed IC₅₀ value of 14.66 ± 2.29 μmol L⁻¹. Docking experiments corroborated by kinetic assay are suggestive of a competitive inhibition mechanism. Derivatives interacted with amino acids from the AChE active site associated to the development of Alzheimer's disease. The results indicate that the compounds synthesized have a high potential as prototypes for the development of new acetylcholinesterase inhibitors.     

Novel plant activators with thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate scaffold： Synthesis and bioactivity

The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.     

Synthesis of novel 1-benzyl/aryl-4-{[(1-aryl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]methyl}-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole derivatives and evaluation of their antimicrobial activity

A series of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives were synthesized via Cu(I) catalyzed reaction between terminal alkyne and substituted aryl or benzyl azides. The synthesized triazoles were characterized by 1H NMR, 13C NMR, IR, and mass spectral techniques. All the synthesized compounds were screened for their antimicrobial activity.     

Microwave synthesis,characterization and antimicrobial study of new pyrazolyl-oxopropyl-quinazolin-4(3H)-one derivatives

Heterocyclic compounds containing pyrazolyl-oxopropyl-quinazolin-4(3H)-one are reported to possess significant biological activity. Syntheses of 6-bromo-2-(3-chloro-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 2 6-bromo-3-(4-fluorophenyl)-2-(3-hydrazinyl-2-oxopropyl)quinazolin-4(3H)-one 3 and 6-bromo-2-(3-(3-(4-(1-(2-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-ylideneamino)phenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 5a–j using microwave irradiation have been described. These compounds have been characterized on the basis of the UV, IR, ¹H NMR, ¹³C NMR, Mass and elemental analysis. Compounds have been evaluated for their antimicrobial activity.     

Synthesis of new transition metal complexes of 1H-perimidine derivatives having antimicrobial and anti-inflammatory activities

New series of 1H-perimidine-2-thiol derivatives and (2-substituted-1H-perimidin-1-yl)ethane-1,2-dione derivatives and their ligands (C₂₄H₁₄N₄S₂O₂) H₂L¹ and (C₂₆H₁₈N₄S₂O₂) H₂L² have been synthesized with transition metal ions, e.g., Copper (II), Silver (I), Cobalt (II) and Ruthenium (III) were prepared and evaluated for their antimicrobial, analgesic and anti-inflammatory activities. The synthesized compounds and their complexes were characterized by elemental analysis, ¹H NMR, IR, MS, molar conductance, thermal gravimetric analysis and electronic spectra. All results revealed that compounds 3 and 13 exhibited high inhibitory effects against some bacterial strains by the disc diffusion method. On the other hand, compounds 2, 3, 7 and 12 displayed potent anti-inflammatory activity.