Design,Synthesis, and Antifungal Activities of New β‐Methoxyacrylate Analogues

Strobilurins have become one of the most important classes of agricultural fungicides. To search for new strobilurin derivatives with high activity against resistant pathogens, a series of new β‐methoxyacrylate analogues containing substituted pyrimidine in the side chain with strobilurin pharmacophore were synthesized and their biological activities were tested. The compounds were confirmed and characterized by ¹H‐NMR, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds 1 exhibited potent antifungal activities against Colletotrichum orbiculare, Botrytis cinerea Pers and Phytophthora capsici Leonian at a concentration of 50 μg mL^?1. Notably, compound 1b (R = 2,5‐dimethylphenyl) showed better antifungal activity against all the tested fungi than the commercial strobilurin fungicide azoxystrobin.     

Synthesis,Characterization, and Biological Evaluation of Some Tri‐Substituted Imidazole/thiazole Derivatives

A novel compound series of tri‐substituted imidazole/thiazole derivatives ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i ) were prepared by Radziszewski reaction. Benzil ( 1 ), ammonium acetate or ammonium thiocynate, and 1‐phenyl‐3‐(p‐substituted phenyl)‐1H‐pyrazole‐4‐carbaldehyde ( 2a , 2b , 2c , 2d , 2e , 2f , 2g ) were reacted to give the desired product. Synthesized compounds were characterized by elemental analysis (CHNS) and spectral analysis (FTIR, ¹H and ¹³C FT NMR, and LC–MS). All the compounds were screened for their antibacterial, antifungal, and antimycobacterial activities. Antimicrobial activity was evaluated against some bacterial strains such as Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), and the H₃₇Rv strain of Mycobacterium tuberculosis, and the fungal activity was observed against strains, for example, Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), and Aspergillus clavatus (MTCC 1323). All the synthesized compounds were found to possess moderate to excellent activity against the above selected strains.     

Design,synthesis and biological evaluation of novel N1,N8-bis(((4-((5-aryl-1,3,4-oxadiazol-2-yl)methoxy)phenyl)amino)oxy)-1-naphthamide derivatives

A new series of 1,8-bis(4-((5-phenyl-1,3,4-oxadiazol-2-yl) methoxy)-substituted aryl) naphthalene-1,8-dicarboxamide derivatives (6a–j) were synthesized in the presence of POCl₃ and obtained good yields. All the synthesized novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, HRMS spectroscopic data and elemental analysis. All the synthesized compounds evaluated for their antibacterial and antifungal activities. The antibacterial activity screened against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli and used standard reference drug ciprofloxacin. The antifungal activity screened against two pathogenic fungal strains Aspergillus niger and Candida albicans used a reference standard drug Voriconazole. All these compounds (6a–j) demonstrate good antibacterial and antifungal activity. Among them, compounds 6h and 6c show highest antibacterial and antifungal activity.     

Synthesis,antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives

We describe the synthesis of some novel p-tert-butylcalix[4]arene-based (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives ( 4a–e ). These compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene ( 1 ) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate ( 3a–e ) in the presence of potassium carbonate as a weak base and dry acetone as the solvent. All the newly synthesized calix[4]arene derivatives were characterized by elemental analysis and various spectroscopic methods such as FT-IR, ¹H NMR,¹³C NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for their antibacterial and antifungal activities against Escherichia coli and Aspergillus fumigates in comparison with enrofloxacin and amphotericin as reference drugs, which are normally used for treating such infections. The synthesized compounds showed different inhibition zones against the tested bacteria and fungi. Compound 4c was found to be most effective against A. fumigates, whereas compound 4e was found to be equally effective against E. coli and A. fumigates.     

One-pot facile synthesis,crystal structure and antifungal activity of 1,2,3-triazoles bridged with amine-amide functionalities

A library of twenty five 1,2,3-triazoles bridged with amine-amide functionalities have been synthesized from reaction of N-substituted(prop-2-yn-1-yl)amines (2a–2e), 2-bromo-N-arylacetamides (4a–4e) and sodium azide through copper(I)-catalyzed alkyne-azide cycloaddition. The synthesized compounds were characterized by using FTIR, ¹H NMR, ¹³C NMR, and HRMS techniques. The structures of synthesized 5a (CCDC 1569245) and 5h (CCDC 1569249) were also confirmed by X-ray crystallography. Antifungal evaluation of newly synthesized triazoles was carried out against – Candida albicans and Aspergillus niger. Biological screening of synthesized 1,2,3-triazoles revealed moderate to good antifungal activity against tested strains.     

Synthesis,antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles

In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, ¹H-NMR, ¹³C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250–7.8 µg mL^?1 against the tested microorganisms. Among the newly synthesized derivatives 3–22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than standard drugs ampicillin trihydrate and rifampicin against Pseudomonas aeruginosa and its gentamicin-resistant isolate. The 2D-QSAR (Quantitative Structure–Activity Relationship) analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) was also performed by using multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.     

Microwave-Assisted Synthesis of 2-Long Alkenyl Chain Benzoxazoles and Naphtho[2,3-d]oxazoles and Their Antimicrobial Evaluation

A microwave-assisted combinatorial synthesis of 2-long alkenyl chain benzoxazoles and naphtho[2,3-d]oxazoles with a catalytic amount of phosphorus pentasulphide at ambient pressure has been developed. This procedure constitutes a simple, practical, and green synthetic method for benzoxazoles and their structural analogs. All the compounds [2(a–d) through 6(a–d)] have been screened for antibacterial and antifungal activity. The compounds have showed good activity against Gram-positive and Gram-negative bacteria. All the compounds have also showed good results against almost all fungal strains. The structures of the synthesized compounds are elucidated by IR, ¹H NMR, ¹³C NMR, MS data, and elemental analysis.     

Synthesis and Characterization of Thiophene‐derived Amido Bis‐nitrogen Mustard and Its Antimicrobial and Anticancer Activities

The thiophene‐derived amido bis‐nitrogen mustard N²,N²,N⁵,N⁵‐tetrakis(2‐chloroethyl)‐3,4‐dimethylthiophene‐2,5‐dicarboxamide was designed and synthesized via five‐step reactions from commercially available 2‐chloroacetonitrile. This target compound was confirmed by ¹H NMR, ¹³C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X‐ray single‐crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug‐resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC‐3), breast carcinoma cell line (MCF‐7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC‐3) at a low dose.     

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,structural characterization,biological activity,and theoretical studies of some novel thioether-bridged 2,6-disubstituted imidazothiadiazole analogues

In this study, thioether-bridged imidazo[2,1-b][1,3,4]thiadiazole derivatives that contained both imidazole and 1,3,4-thiadiazole (compounds 7a-7i and 8a-8i ) were synthesized from the reactions of 2-amino-1,3,4-thiadiazole with phenacyl bromide ( 6a - 6i ) (at yields of 59% to 74%). The structure of the synthesized compounds was characterized using ¹H NMR, ¹³C NMR, Fourier-transform infrared spectroscopy, elemental analysis, mass spectroscopy, and X-ray diffraction analysis. Mycelial growth, mycelial growth inhibition, minimum inhibitory concentration, minimum fungicidal concentration, and lethal dose values against various plant pathogenic fungi were determined for all of the target compounds synthesized in the study. The test results showed that most of the compounds had moderate to good antifungal activity. In addition, the absorption, distribution, metabolism, excretion (ADME) parameters of the compounds were calculated, and it was observed that all of the compounds met the drug-likeness rules in general. Finally, using docking simulations, it was found that compounds 7h , 7i , 8h , and 8i showed high affinity to PDB ID:5TZ1, which is an CYP51 antifungal target structure.     

Synthesis and antimicrobial activity of new 2-((1-furan-2-yl)ethylidene)hydrazono)-4-phenylthiazol-3(2H)-amine derivatives and their schiff bases with 4-nitrobenzaldehyde

Abstract

A new series of 2-((1-furan-2-yl)ethylidene)hydrazono)-4-substitutedphenylthiazol-3(2H)-amines (2a–2o) and their Schiff bases (3a–3o) from 4-nitrobenzaldehyde were synthesized. The chemical structures of all the synthesized compounds were confirmed by their IR, ¹H-NMR, ¹³C-NMR spectroscopy and mass spectrometry. They were screened for their antimicrobial and antifungal activities. Additionally, in vitro cytotoxic acivity of the most active antifungal compound (3o) and ketoconazole was determined in NIH/3T3 cells by MTT assay. Compound 2i (4-{3-Amino-2-[(1-(furan-2-yl)ethylidene)hydrazono]-2,3-dihydrothiazol-4-yl}phenol) showed the greatest antifungal activity among the newly synthesized derivatives. Schiff bases (3c-3n) displayed an undeniable fungicidal action against Candida parapsilosis ATCC 22019 as intense as the reference ketoconazole. In addition, the most active Schiff base 3o (2-[(1-(Furan-2-yl)ethylidene)hydrazono]-N-(4-nitrobenzylidene)-4-(2,3,4-trichloro phenyl)thiazol-3(2H)-amine) showed the highest antifungal activity against both Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019, and was as potent as ketoconazole. Moreover, compound 3o was found to be non-cytotoxic against NIH/3T3 cells.     

Synthesis,Photophysical Properties,and Antimicrobial Activity of Novel Styryl Colorants Derived from 7‐Methoxy‐1,4‐diphenethyl‐1,2,3,4‐tetrahydroquinoxaline‐6‐carbaldehyde

The novel 1,4‐diphenethyl‐1,2,3,4‐tetrahydro‐7‐methoxyquinoxalin‐6‐carbaldehyde was synthesized by reductive alkylation of 6‐methoxy quinoxaline with phenyl acetic acid and was further subjected to Knoevenagel condensation with various active methylene compounds to synthesize novel styryl colorants. Photophysical properties of styryl colorants were studied using UV–visible and fluorescence spectroscopy. These colorants displayed orange to violet hue and showed fluorescence emission maxima in the region of 560–640 nm, and displayed a large Stokes shift (85–104 nm). Compounds were subjected to thermogravimetric analysis which showed excellent stability up to 310°C. These styryl compounds were evaluated for their antimicrobial study as antifungal against Candida albicans C. albicans and Aspergillus niger and antibacterial against Escherichia coli and Staphylococcus aureus. The results revealed good antimicrobial activity against tested organisms. The synthesized chromophores were characterized using elemental analysis, FTIR, ¹³C‐NMR and ¹H‐NMR spectroscopy and mass spectrometry.     

Synthesis and antifungal activity of trichodermin derivatives

<正>A series of derivatives were synthesized from trichodermin(1) which was an antifungal metabolite produced by Trichoderma taxi sp.nov.Their structures were confirmed by ~1H NMR,MS spectrum.Their antifungal activities were evaluated in vitro.The preliminary structure activity relationships(SAR) results indicated that the double bond,epoxide moiety and ester group were main pharmacophore elements,the stereochemistry of C4 position played a key role as well,and the compounds 1e-1g displayed stronger antifungal activity against Magnaporthe grisea than 1.     

Synthesis and Bioactivities of Novel 1‐(3‐Chloropyridin‐2‐yl)‐N‐Substituted‐5‐(Trifluoromethyl)‐Pyrazole Carboxamide Derivatives

A series of novel 1‐(3‐chloropyridin‐2‐yl)‐N‐substituted‐5‐(trifluoromethyl)‐pyrazole carboxamide derivatives TC₁ , TC₂ , TC₃ , TC₄ , TC₅ , TC₆ , TC₇ , TC₈ , TC₉ , TC₁₀ , TC₁₁ were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. All the target compounds were tested in vitro for their antibacterial activities and antifungal activities. The preliminary bioassays indicated that compound TC₆ exhibited excellent activity against Xanthomonas oryzae (94.9% and 84.9%) at different concentrations (200 µg/mL and 100 µg/mL), which was higher than that of Bismerthiazol (94.6% and 64.0%), respectively. At the same time, most of the compounds exhibited moderate antifungal activities against four kinds of phytopathogenic fungi     

Synthesis,Structural Characterization,and Biological Evaluation of Novel Substituted 1,3‐Thiazole Derivatives Containing Schiff Bases

In this study, thiazole derivatives containing Schiff bases ( 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f ) were synthesized in moderate to high yields (49–94%) using the Hantzsch reaction with thiosemicarbazone derivatives ( 5a , 5b , 5c ) and 2‐bromo‐1‐phenylethanone derivatives ( 6a , 6b , 6c , 6d , 6e , 6f ). The structures of synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, elemental analyses, mass spectroscopy and X‐ray diffraction analysis techniques. Moreover, the synthesized compounds were tested for their in vitro antifungal activity and most of them exhibited moderate to good activity against Fusariumoxysporumf.sp. lycopersici.      

Convenient Synthesis and Biological Activity of Mono and Diacyl 2,5‐Dimercapto‐1,3,4‐thiadiazole Derivatives

New derivatives of 2,5‐dimercapto‐1,3,4‐thiadiazole substituted both at one or two exocyclic sulfur atoms with a series of aroyl or ethoxycarbonyl groups were synthesized in reactions of 2,5‐dimercapto‐1,3,4‐thiadiazole salts with appropriate acid chlorides or ethyl chloroformate in mild conditions. The products were characterized by spectroscopy (¹H NMR, ¹³C NMR, IR, and HRMS). Some from the synthesized compounds were screened in vitro and in vivo for antibacterial and antifungal activities against a panel of reference strains of microorganisms. The study revealed that ethyl S‐(5‐mercapto‐1,3,4‐thiadiazol‐2‐yl) carbonothioate seems to be the most active and versatile compound against Gram‐positive bacteria, Gram‐negative bacteria, and plant pathogenic fungi.     

Synthesis,reactions, and spectral characterization of some new biologically active compounds derived from thieno[2,3-c]pyrazole-5-carboxamide

The starting compound 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide (1) , that has been previously synthesized according to the literature procedure, underwent a reaction with the anhydride of phthalic acid either in AcOH or DMF to give isoindolinylpyrazole-5-carboxamide 3 and pyrazolothienopyrimidoisoindoledione 4 , respectively. Also, it was subjected to react with diethylmalonate followed by hydrazinolysis by hydrazine hydrate to yield the pyrazolothienopyrimidinyl acetohydrazide 5 . The carbohydrazide derivative 5 was used as a key intermediate for the preparation of other new heterocyclic systems containing pyrazolylacetyl pyrazolothienopyrimidines and pyrazolothieno-pyrimidotriazepine compounds 6–11 . The structures of these new heterocycles have been characterized by using analytical and spectroscopic analyses (IR, ¹H-NMR, ¹³C-NMR and MS). Some derivatives of the synthesized compounds exhibited remarkable antibacterial and antifungal activities against many bacterial and fungal strains.     

Design,synthesis, and evaluation of new 4(3H)-quinazolinone derivatives containing a pyrazole carboxamide moiety

A total of 15 new 4(3H)-quinazolinone derivatives containing a pyrazole carboxamide moiety were designed and synthesized in this study. The structures of the target compounds were elucidated using ¹H NMR, ¹³C NMR, MS, and elemental analysis. Then, antifungal activities against Gibberella zeae (G. zeae), Fusarium oxysporum (F. oxysporum), Cytospora mandshurica (C. mandshurica), Phytophthora infestans (P. infestans), and Pellicularia sasakii (P. sasakii) as well as antibacterial activities against Ralstonia solanacearum (R. solanacearum) and Xanthomomu oryzae pv. oryzae (Xoo) were assayed. Bioassay results revealed that the target compounds have certain antifungal and antibacterial activities. Especially, compound 5-chloro-1,3-dimethyl-N-(2-(4-oxo-2-(m-tolylamino)quinazolin-3(4H)-yl)ethyl)-1H-pyrazole-4-carboxamide ( 7g ) exhibited better antibacterial activities against R. solanacearum (60%) and Xoo (53%) than those of thiodiazole-copper (52% and 38%, respectively) at 200 μg/ml. This study provided a practical tool for guiding the design and synthesis of novel and more promising active small molecules of 4(3H)-quinazolinone derivatives containing a pyrazole carboxamide moiety for controlling plant bacterial and fungal diseases.     

Synthesis,biological evaluation,and molecular docking studies of novel pyrazole,pyrazoline-clubbed pyridine as potential antimicrobial agents

We have prepared 15 hybrid pyrazole, pyrazoline-clubbed pyridine–containing compounds (5a-o) and tested for their antibacterial and antifungal activities for the development of potential antimicrobial agents. The structures of this novel series were characterized by various spectral techniques like IR, ¹H NMR, ¹³C NMR, LC–MS, and elemental analysis. The synthesized compounds 5d, 5e, 5i, 5k, 5m, and 5o exhibited significant antimicrobial activity in the comparison of standard drugs. Molecular docking studies that have been carried out to emphasize the binding orientations of these molecules were in good compliance with crystal structure interactions. The predicted drug-likeness (ADME) properties were found to be in the acceptable range.     

Design,Synthesis, Antimicrobial Evaluation,and Laccase Catalysis Effect of Novel Benzofuran–Oxadiazole and Benzofuran–Triazole Hybrids

Novel structural hybrids of benzofuran–oxadiazole and benzofuran–triazole have been synthesized and evaluated for their potential against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. The excellent antibiotic activity was shown by compounds 5c and 9c against S. aureus with minimum inhibitory concentration values in 1.74–5.16 mg/mL range. The estimation of in vitro antifungal activity of synthetic compounds was performed against Trichoderma harzianum, Aspergillus niger, and Metarhizium anisopliae. Among compounds 5a – 5j , only 5h and 5i showed promising antifungal potential against T. harzianum and A. niger, whereas compound 5j showed enhanced antifungal effect only against A. niger when their activity values were compared with standard drug amphotericin. No pronounced antifungal activity was shown by synthesized compounds 9a–j , except for compound 9g , which was active against all fungal strains having minimum inhibitory concentration values in 1.90–2.03 mg/mL range. In addition to antimicrobial evaluation, the synthesized compounds were also analyzed to study their effects on the catalytic potential of laccase, and it was found that among all, compound 9b showed very strong activity with maximum relative reactivity of 145% at 0.03‐mM concentration.