Design,Synthesis and Evaluation of Antibacterial Effects of a New Class of Piperazinylquinolone Derivatives

Pentafluoropyridine derivatives and cyanuric chloride were used for the synthesis of new piperazinylquinolone derivatives. These reactions provided N‐fluoropyridiyl and N‐cyanoryl chloride piperazinylquinolone derivatives in good yields. Synthesized compounds were evaluated for their antibacterial activities. These compounds displayed good to excellent antibacterial activities.     

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

A Simple,Efficient One‐Pot Synthesis of 2‐Isoxazoline Derivatives and their Antimicrobial Activity

Synthesis of substituted 2‐isoxazolines derivatives with sulfone functional groups was accomplished by 1,3‐dipolar cycloaddition reaction. The 1,3‐dipolar nitrile oxides generated in situ by reacting α‐formaldoximes with N‐bromosuccinimide in the presence of triethylamine on reaction with activated alkenes in toluene at room temperature afford the corresponding 2‐isoxazolines in high yields. All the 2‐isoxazoline derivatives were assayed for their antibacterial activities against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa and antifungal activities against Aspergillus niger and Candida albicans. Most of the compounds showed good antibacterial and antifungal activities.     

Microwave promoted synthesis and antimicrobial activity of 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives

The present paper describes an optimized reaction condition for the microwave promoted synthesis of newer 3-thiazole substituted 2-styryl-4(3H)-quinazolinone derivatives, which in turn were prepared in good yield by the treatment of various 2-styryl benzoxazinone derivatives with various 2-aminothiazoles using co-solvent under microwave irradiation. All the compounds were characterized by various spectroscopic techniques and analytical methods. All newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus megaterium,Bacillus subtilis, and Aspergillus niger.     

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.     

Synthesis,antimicrobial activity,and molecular docking study of formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamides

In the present study, substituted formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamide derivatives ( 6a – k ) have been designed and synthesized employing click chemistry approach and evaluated for their in vitro antifungal and antibacterial activities. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral techniques. Among the screened compounds, 6d , 6e , 6j , and 6k have shown good antifungal and antibacterial activities. Compound 6k has shown very effective antimicrobial activity. We further performed exploratory docking studies on microbial DNA gyrase to rationalize the in vitro biological data and to demonstrate the mechanism of antimicrobial activity. This is the first report to demonstrate the formylnaphthalenyloxymethyl, triazole, and N‐phenylacetamide hybrids as potential antimicrobial agents.     

Synthesis of Novel 1‐(5‐(Benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea Derivatives and Evaluation of Their Antimicrobial Activities

A new series of 1‐(5‐(benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea derivatives ( 1a – j ) were designed and synthesized. For the first time, (i) a new process was developed for N‐methylation of 1,3,4‐thiadiazole moiety using dimethyl carbonate an environmentally benign reagent in presence of N,N,N′,N′‐tetramethylethylenediamine and (ii) the sulfide was selectively oxidized to sulfoxide in higher yield by using chlorine (g) in aqueous acetic acid media under mild reaction condition. The synthesized compounds ( 1a – j ) were investigated for their antimicrobial activities. The tested compounds ( 1a – j ) were exhibited moderate to excellent antibacterial activities against both Gram‐positive and Gram‐negative bacterial strains. The same compounds exhibited good antifungal activities against selected fungal strains. Particularly, the compounds 1b , 1d , 1h , and 1i were proved to be promising leads exhibiting both antibacterial and antifungal activities compared with standard drugs, ciprofloxacin, and fluconazole. The presence of 1,3,4‐thiadiazole moiety has a significant role in the display of antimicrobial activity. In addition, the presence of both sulfinyl and thiourea or urea functionalities has enhanced the activity as per obtained antimicrobial activity data.     

Synthesis and biological activities of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety

A series of benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety were designed, synthesized and evaluated for their antibacterial, antifungal and antiviral activities. The bioassay results indicated that most of target compounds showed good antiviral activities against tobacco mosaic virus (TMV) and antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). Especially, the anti-Xoo effect of title compounds 5k (N-(5-methoxybenzo[d]thiazol-2-yl)-2-((5-(2-tolyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) and the anti-Rs effect of title compounds 5a (N-(5-nitrobenzo[d]thiazol-2-yl)-2-((5-(4-(trifluorom ethyl)phenyl)-1,3,4-thiadiazol-2-yl)thio)acetmide) respectively reached 52.4% and 71.6% at 100?µg/mL, which are superior to that of bismerthiazol (32.0% and 52.3%). In addition, the protective and inactivation activities of title compound 5i (N-(5-methoxybenzo [d]thiazol-2-yl)-2-((5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl)thio)acetamide) against TMV were 79.5% and 88.3%, respectively, which are better than that of ningnanmycin (76.4% and 86.8%). The above research showed that benzothiazole derivatives bearing a 1,3,4-thiadiazole moiety may be used as potential molecular templates in searching for highly-efficient antiviral and antibacterial agents.     

Synthesis and antibacterial activity of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones

A series of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones containing a carbonyl related functional groups (oxo- or oxyimino-) on the ethyl spacer was synthesized and evaluated for antibacterial activity. The synthesis of N-[2-(2-naphthyl)ethyl]piperazinyl quinolones was achieved through the versatile and efficient synthetic route that involved reaction of piperazinyl quinolones with appropriate α-bromoketone or α-bromooxime derivatives. The structures of new compounds were confirmed by elemental analysis, IR and NMR spectra. Antibacterial data indicated that some of the new N-[2-(2-naphthyl)ethyl]piperazinyl quinolones showed good antibacterial activity and modification of the position 8 and N-1 substituent on quinolone ring, and ethyl spacer functionality produced significant changes in activity against Gram-positive and Gram-negative bacteria.     

Synthesis and Antibacterial Activity of Novel 5,5′-(Pyridine-2,6-Diyl)bis(4-Arylideneamino-3-Mercapto-1,2,4-Triazole)-Related Derivatives

The reaction of 5,5′-(pyridine-2,6-diyl)bis(4-amino-3-mercapto-1,2,4-triazole) with various aromatic aldehydes in acetic acid yielded the corresponding 5,5′-(pyridine-2,6-diyl)bis(4-arylideneamino-3-mercapto-1,2,4-triazole) derivatives. The structures of the synthesized compounds as well as their intermediates were confirmed by elemental analysis, infrared spectra, ¹H NMR spectra and mass spectra studies. All the synthesized title compounds were screened for their antibacterial activities, and the preliminary results revealed that some of them showed good activities against Escherichia coli and Pseudomonas aeruginosa.     

Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1 H NMR, 13 C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazolethione and its triazolium derivatives displayed the most potent activities against all the tested strains.     

Efficient preparation of secondary aminoalcohols through a Ti(IV) reductive amination procedure. Application to the synthesis and antibacterial evaluation of new 3β-N-[hydroxyalkyl]aminosteroid derivatives

An efficient method for the synthesis of various secondary aminoalcohols through a titanium(IV) isopropoxide-mediated reductive amination reaction of ketones is reported. Thus, different ketones gave the expected products in moderate to excellent yields up to 89% in numerous cases. A series of 3β-N-[hydroxyalkyl]aminosteroid derivatives were prepared according to this methodology and evaluated for their in vitro antimicrobial properties against human pathogens. All the compounds showed moderate to excellent activities against Gram-positive bacteria exhibiting similar results against Staphylococcus aureus and Streptococcus faecalis with Minimum Inhibitory Concentrations (MICs) varying from 3.12 to 25 μg/mL. No significant antibacterial activities are encountered against Gram-negative bacteria.     

Synthesis and antibacterial evaluation of novel Schiff base derivatives containing 4(3<Emphasis Type="Italic">H</Emphasis>)-quinazolinone moiety

A series of novel Schiff base derivatives containing 4(3H)-quinazolinone moiety were synthesised and their antibacterial activities against tobacco and tomato bacterial wilts evaluated in vitro. Out of the synthesised compounds, 5g, 5j, 5n, 5m and 5p exhibited excellent antibacterial activities against tobacco bacterial wilt, with half maximal effective concentrations (EC50): 160.34, 158.03, 125.94, 148.09 and 133.67 (all in εg mL^?1), respectively, which were better than the EC50 of thiodiazole–copper (216.70 εg mL^?1). Compounds 5j, 5n and 5o also showed good antibacterial activities against tomato bacterial wilt, with EC50 of 95.20, 90.03 and 83.21 (all in εg mL^?1) respectively, which were better than the EC50of thiodiazole–copper (99.80 εg mL^?1). These compounds may prove to be useful as potential antibacterial agents.     

Antibacterial activity of N-quaternary chitosan derivatives: Synthesis, characterization and structure activity relationship (SAR) investigations

Quaternary N-(2-(N,N,N-tri-alkyl ammoniumyl and 2-pyridiniumyl) acetyl) derivatives of chitosan polymer, chitooligomer, and glucosamine (monomer) were synthesized for the purpose of investigating the structure activity relationship (SAR) for the antibacterial effect. Novel methods were used in the synthesis. The final chitosan and chitooligomer derivatives could thus be obtained in two steps without prior protection of the hydroxyl groups. However, in order to obtain chitosan derivatives with the bulky N,N-dimethyl-N-dodecyl- and N,N-dimethyl-N-butyl side chains three steps were needed, starting from 3,6-O-di-tert-butyldimethylsilyl chitosan (3,6-O-di-TBDMS chitosan) as the key intermediate. The quaternary ammoniumyl acetyl derivatives of glucosamine were synthesized from glucosamine or tetra-O-acetylglucosamine. N,N,N-trimethyl chitosan (TMC) was used as reference compound for investigation of antibacterial activity. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC and MLC for activity against clinically important Gram-positive strains Staphylococcus aureus (ATCC 25923), and S. aureus (MRSA) (ATCC 43300), and Gram-negative strains of Escherichia coli (ATCC 25922), P. aeriginosa (ATCC 27853) and Enterococcus facialis (ATCC 29212). The MIC values for the compounds ranged from 8 to ?8192 mg/L. In general the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitooligomer and glucosamine monomer were more active against bacteria than derivatives with shorter alkyl chains. In contrast the N-(2-(N,N-dimethyl-N-dodecyl ammoniumyl) acetyl) derivatives of chitosan were less active than derivatives with N-(2-N,N,N-trimetylammoniumyl) acetyl or N-(2-(N-pyridiniumyl) acetyl) quaternary moiety. N,N,N-trimethyl chitosan (TMC) was the most active compound in this study.     

Antibacterial activity of methylated chitosan and chitooligomer derivatives: Synthesis and structure activity relationships

The purpose of this study was to synthesize series of methylated chitosaccharide derivatives, possessing various degree of methylation, and to determine their structure activity relationship (SAR) with regard to their antibacterial effect against Staphylococcus aureus. Chitosan polymer and chitooligomers were used as starting materials and were methylated by reaction with methyl iodide. Depending on the reaction conditions the degree of N-quaternization ranged from 0% to 74%, with varying degree of N,N-dimethylation, N-monomethylation and O-methylation. More selective N-quaternization could be obtained with protection group strategy. At pH 5.5 the chitosaccharide polymers and their methylated derivatives were active against S. aureus with minimal inhibitory concentration (MIC) ranging from 16 to 512 μg/mL. At pH 7.2 the non-quaternized derivatives were inactive but their highly N-quaternized derivatives showed MIC as low as 8 μg/mL. The chitooligomers, as well as their derivatives, were inactive at both pH’s. The SAR studies revealed that N-quaternization was mainly responsible for the antibacterial effects at pH 7.2, whereas it did not contribute to the antibacterial activity under acidic conditions.     

Design,Synthesis, and Bioactivity Evaluation of New Thiochromanone Derivatives Containing a Carboxamide Moiety

In this study, using the botanical active component thiochromanone as the lead compound, a total of 32 new thiochromanone derivatives containing a carboxamide moiety were designed and synthesized and their in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were determined, as well as their in vitro antifungal activities against Botryosphaeria dothidea (B. dothidea), Phomopsis sp., and Botrytis cinerea (B. cinerea). Bioassay results demonstrated that some of the target compounds exhibited moderate to good in vitro antibacterial and antifungal activities. In particular, compound 4e revealed excellent in vitro antibacterial activity against Xoo, Xoc, and Xac, and its EC₅₀ values of 15, 19, and 23 μg/mL, respectively, were superior to those of Bismerthiazol and Thiodiazole copper. Meanwhile, compound 3b revealed moderate in vitro antifungal activity against B. dothidea at 50 μg/mL, and the inhibition rate reached 88%, which was even better than that of Pyrimethanil, however, lower than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing a carboxamide moiety.     

<em>N</em>-Substituted 5-Chloro-6-phenylpyridazin-3(2<em>H</em>)-ones: Synthesis, Insecticidal Activity Against <em>Plutella xylostella </em>(L.) and SAR Study

A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H)-one derivatives were synthesized based on our previous work; all compounds were characterized by spectral data and tested for in vitro insecticidal activity against Plutella xylostella. The results showed that the synthesized pyridazin-3(2H)-one compounds possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h which showed > 90% activity at 100 mg/L. The structure-activity relationships (SAR) for these compounds were also discussed.     

Synthesis,Dissociation Constants,and Antimicrobial Activity of Novel 2,3‐Disubstituted‐1,3‐thiazolidin‐4‐one Derivatives

In this article, a new series of 2,3‐disubstituted‐1,3‐thiazolidin‐4‐one derivatives have been designed, synthesized, and evaluated as antimicrobial agents. New compounds were prepared by the cyclization reaction of N‐substituted carboxylic acid hydrazide derivatives with mercaptoacetic acid. The structures of the obtained compounds were confirmed by means of IR, ¹H NMR, and ¹³C NMR spectra. The dissociation constants were determined using spectrophotometric method. All synthesized compounds were tested for their in vitro antibacterial and antifungal activities using the broth microdilution method.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.     

Synthesis of novel coumarin substituted amide derivatives and their antibacterial activities

A series of novel coumarin substituted amide derivatives were synthesized and evaluated for their antibacterial activities. Result indicated that compounds 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 3n, 3o and 3q exhibited excellent antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas citri subsp. Citri (Xcc) in vitro, which were better than those of commercial agricultural antibacterial thiodiazole-copper. The title compounds with electron-withdrawing group showed better antibacterial activities than those of compounds with electron-donating group, and the title compounds bearing the same substituent group exhibited better antibacterial activities against Xcc than antibacterial activities against Xoo.