The synthesis and antistaphylococcal activity of N-sulfonaminoethyloxime derivatives of dehydroabietic acid

A series of N-sulfonaminoethyloxime derivatives of dehydroabietic acid were synthesized and investigated for their antibacterial activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Most of the target compounds having chloro, bromo, trifluoromethyl phenyl moiety exhibited potent in vitro antistaphylococcal activity. The meta-CF₃ phenyl derivative T23 showed the highest activity with MIC of 0.39–0.78?μg/mL against S. aureus Newman, while several analogues showed similar potent antibacterial activity with MIC values between 0.78 and 1.56?μg/mL against five multidrug-resistant S. aureus. The stability of T35 in plasma of SD rat and the cellular cytotoxicity were also evaluated.     

Substituted 1,6-diphenylnaphthalenes as FtsZ-targeting antibacterial agents

Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z-ring structure comprised of FtsZ subunits. Agents that disrupt Z-ring formation have the potential, through this unique mechanism, to be effective against several of the newly emerging multidrug-resistant strains of infectious bacteria. Several 1-phenylbenzo[c]phenanthridines exhibit notable antibacterial activity. Based upon their structural similarity to these compounds, a distinct series of substituted 1,6-diphenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. In addition, the effect of select 1,6-diphenylnaphthalenes on the polymerization dynamics of S. aureus FtsZ and mammalian β-tubulin was also assessed. The presence of a basic functional group or a quaternary ammonium substituent on the 6-phenylnaphthalene was required for significant antibacterial activity. Diphenylnaphthalene derivatives that were active as antibiotics, did exert a pronounced effect on bacterial FtsZ polymerization and do not appear to cross-react with mammalian tubulin to any significant degree.     

Synthesis and on-target antibacterial activity of novel 3-elongated arylalkoxybenzamide derivatives as inhibitors of the bacterial cell division protein FtsZ

Novel 3-elongated arylalkoxybenzamide derivatives were designed, synthesized and evaluated for their cell division inhibitory activity and antibacterial activity. Among them, the subseries of 3-alkyloxybenzamide derivatives exhibited greatly improved on-target activity against Bacillus subtilis and Staphylococcus aureus, and remarkably increased antibacterial activity against B. subtilis ATCC9372, penicillin-susceptible S. aureus ATCC25923, methicillin-resistant S. aureus ATCC29213 (MRSA) and penicillin-resistant S. aureus PR compared with 3-methoxybenzamide. In contrast, the subseries of 3-phenoxyaklyloxybenzamide, 3-heteroarylalkyloxybenzamide and 3-heteroarylthioalkyloxybenzamide derivatives only showed a significant improvement in on-target activity and antibacterial activity against B. subtilis ATCC9372.     

Design,synthesis and antibacterial evaluation of honokiol derivatives

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1 × MIC and 4 × MIC.     

Synthesis,antibacterial and antifungal activities of some carbazole derivatives

A series of N-substituted carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacillus proteus, Candida albicans and Aspergillus fumigatus by two fold serial dilution technique. Some of the synthesized compounds displayed comparable or even better antibacterial and antifungal activities than reference drugs fluconazole, chloramphenicol and norfloxacin against tested strains.     

Bernthsen synthesis,antimicrobial activities and cytotoxicity of acridine derivatives

The condensation reaction of diphenylamine with 2-oxo-2H-(substituted chromen)-4-yl acetic acid in presence of anhydrous zinc chloride afford 4-(acridine-9-ylmethyl)-2H-(substituted chromen)-2-one. The synthesized compounds were characterized by spectral studies and elemental analysis and screened for their in vitro antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes (gram +ve), Escherichia coli, Pseudomonas aeruginosa (gram ?ve) and antifungal activity against Aspergillus niger and anticancer activity (HL-60, Hep-2 & HEK293T) by MTT assay. Chloro substituted compounds showed antimicrobial and anticancer activity with IC₅₀ values in the low micromolar range.     

Synthesis,molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents

Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4m represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 μg/mL and it showed the most potent activity against S. aureus TyrRS with IC₅₀ of 0.0024 μM. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode.     

Design and synthesis of biaryloxazolidinone derivatives containing amide or acrylamide moiety as novel antibacterial agents against Gram-positive bacteria

A series of novel biaryloxazolidinone derivatives containing amide and acrylamide structure were designed, synthesized and evaluated for their antibacterial activity. Most compounds generally exhibited potent antibacterial activity with MIC values of 1 μg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as positive controls. Compound 17 exhibited good antibacterial activity with MIC values of 0.5 μg/mL against S. aureus, MRSA, MSSA and VRE and 0.25 μg/mL against LREF. The results indicated that compound 17 might serve as a potential hit-compound for further investigation.     

Design,synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents

Twenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, ¹H NMR, ¹³C NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00–0.39 µg/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 µg/mL. Activities of compounds 1–21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC₅₀ value of <1.23 μg/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.     

Design,synthesis and biological activity evaluation of novel 2,6-difluorobenzamide derivatives through FtsZ inhibition

Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25–1 μg/mL, and good activity (MIC < 10 μg/mL) against both susceptible and resistant Staphylococcus aureus. Additionally, all the three compounds displayed potent cell division inhibitory activity with MIC values of below 1 μg/mL against Bacillus subtilis and Staphylococcus aureus.     

Design,synthesis, biological evaluation and molecular docking studies of novel pleuromutilin derivatives containing nitrogen heterocycle and alkylamine groups

A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The in vitro antibacterial activity of these semisynthetic derivatives against four strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus AD3, and S.aureus 144) were evaluated by the broth dilution method. Compound 13 was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 μg/mL). Furthermore, compound 13 was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound 13 exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound 13 showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 μg/mL. Molecular docking study revealed that compound 13 can effectively bind to the active site of the 50S ribosome (the binding free energy = −9.66 kcal/mol).     

Novel urea and thiourea derivatives of thiazole-glutamic acid conjugate as potential inhibitors of microbes and fungi

Since discovery and development of effective as well as safe drugs has brought a progressive era in human healthcare that is accompanied by the appearance of drug resistant bacterial strains, there is constant need of new antibacterial agent having novel mechanisms of action to act against the harmful pathogens. In the present study, several N-terminal substituted urea/thiourea derivatives were synthesized by the reaction of glutamic acid and 3-(1-piperazinyl)-1,2-benzisothiazole with various substituted phenyl isocyanates/isothiocyanates. Elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectral data confirmed the structure of the newly synthesized compounds. The derivatives were investigated for their antibacterial and antifungal activities against various pathogens of human origin by agar well diffusion method and microdilution method. The preliminary antimicrobial bioassay reveals that the compounds containing fluoro and bromo as substituents showed promising antimicrobial activity.     

Synthesis and antibacterial activity of new fluoroquinolones containing a cis- or trans-cyclohexane moiety

New quinolone derivatives bearing a cis- or trans-cyclohexane side chain at the C-7 position have been synthesized and evaluated for their antibacterial activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using the agar dilution method. The activities of compound 53 against these three bacteria were superior to those of the reference drug lomefloxacin. Compounds bearing a cis-cyclohexane side chain generally exhibited greater antibacterial activity than their corresponding trans-isomers.     

Synthesis and Biological Evaluation of Novel Carbazole Hybrids as Promising Antimicrobial Agents

Two series of carbazole analogs of 8‐methoxy‐N‐substituted‐9H‐carbazole‐3‐carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 μg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 μg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 μg/mL) and S. aureus (MIC: 1.56 μg/mL), respectively.     

A click chemistry approach to pleuromutilin derivatives,evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking

Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (K_D = 2.32 × 10⁻⁸∼5.10 × 10⁻⁵ M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be −12.0 kcal/mol.     

In vitro anti- biofilm and anti-bacterial activity of Sesbania grandiflora extract against Staphylococcus aureus

The main objective of this research is to investigate the anti-biofilm and anti-bacterial activity of Sesbania grandiflora (S. grandiflora) against Staphylococcus aureus. S. grandiflora extract were prepared and analyzed with UV –Vis spectroscopy, Fourier transform infrared spectroscopy, Dynamic light scattering. Biofilm forming pathogens were identified by congo-red assay. Quantification of Extracellular polymeric substance (EPS) particularly protein and carbohydrate were calculated. The efficacy of the herbal extract S. grandiflora and its inhibition against the pathogenic strain of S. aureus was also evaluated. The gradual decrease or disappearance of peaks reveals the reduction of protein and carbohydrate content in the EPS of S. aureus when treated with S. grandiflora. The antibacterial activity of S. grandiflora extract against the bacterial strain S. aureus showed that the extract were more active against the strain. To conclude, anti-biofilm and antibacterial efficacy of S. grandiflora plays a vital role over biofilm producing pathogens and act as a good source for controlling the microbial population.     

Microwave-assisted synthesis and in vitro antibacterial activity of novel steroidal thiosemicarbazone derivatives

Herein, we reported the synthesis of 16 novel steroidal thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides under solvent-free conditions using microwave irradiation. The yields obtained are in the range of 84–96% using microwave method and 46–62% using conventional method. All the synthesized compounds (7a–p) have been characterized by ¹H NMR, ESI-MS, IR and elemental analyses. All the series compounds (7a–p) were evaluated for their antibacterial activity against and the results were compared with the standard drug Amoxicillin. Some of the compounds from the series like 7c, 7o and 7p were equipotent with Amoxicillin against Pseudomonas aeruginosa. Also compound 7h was better than Amoxicillin against Staphylococcus aureus and Bacillus subtilis.     

Design,synthesis, antibacterial activity and physicochemical parameters of novel N-4-piperazinyl derivatives of norfloxacin

We report herein the synthesis of some N-Mannich bases in addition to different N-4 substituents of norfloxacin. The antibacterial activities of the newly synthesized compounds were evaluated and correlated with their physicochemical properties. Results revealed that some of the tested compounds exhibited better inhibitory activities than the reference antibiotic norfloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus strains. Correlation results showed that there is no single physicochemical parameter that can determine the effect of N-4 piperazinyl group on the activity of these fluoroquinolones, where lipophilicity, molecular mass and electronic factors may influence the activity.     

Pyrone derivatives from the marine-derived fungus Nigrospora sp. PSU-F18

Pyrones, named nigrosporapyrones A-D (1-4), and five known compounds were isolated from the marine-derived fungus Nigrospora PSU-F18. Their structures were elucidated on the basis of spectroscopic evidence. The antibacterial activity against the standard Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus was evaluated.     

Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives

A series of 3-[3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl]-2H-chromen-2-one (4a–k) were synthesized by reaction of 3-[2,3-dibromo-3-(substituted phenyl)propanoyl]-2H-chromen-2-one (3 a-k) with phenyl hydrazine in presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in vitro antibacterial activity against gram-positive and gram-negative bacteria. Among the series, compounds 4d, 4h and 4i displayed an encouraging antibacterial activity profile as compared to reference standard drug ciprofloxacin against tested bacterial strains.