Three New Cembranoids from a Xisha Soft Coral Sarcophyton sp.

Chemical investigation of the Xisha soft coral Sarcophyton sp. has led to the isolation of eight cembrane-type diterpenoids, including three new compounds, namely sarcophynoids A-C ( 1 – 3 ), and five known analog compounds ( 4 – 8 ). Their structures were clarified based on spectroscopic analysis, and computer-assisted methods including TDDFT-ECD calculation and the quantum mechanical-nuclear magnetic resonance (QM-NMR) method. All the above compounds were tested for their antibacterial activities. Among them, compounds 4 – 7 and 8 exhibited antibacterial activities against S. aureus, B. subtilis, and P. aeruginosa, with MIC of 4–64 μg/mL.     

Preparation of Some New Pyrazolo[1,5-a]pyrimidines and Evaluation of Their Antioxidant,Antibacterial (MIC and ZOI) Activities,and Cytotoxic Effect on MCF-7 Cell Lines

This study aims to synthesize some novel pyrazolo[1,5-a]pyrimidine derivatives, and investigate their biological activities. These compounds exhibited good to high antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capabilities]. Among them, Ethyl 5-(2-ethoxy-2-oxoethyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate ( 3h ) showed the highest antioxidant activity [Half-maximal Inhibitory Concentration (IC₅₀)=15.34 μM] compared to ascorbic acid (IC₅₀=13.53 μM) as a standard compound. Their antibacterial activities were investigated against two Gram-positive bacteria (Bacillus subtilis, and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas aeruginosa, and Escherichia coli). The results showed that Ethyl 7-hydroxy-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate ( 3i ) has the best antibacterial activity against Gram-positive B. subtilis [Zone of Inhibition (ZOI)=23.0±1.4 mm, Minimum Inhibitory Concentration (MIC)=312 μM]. Also, the cytotoxicity of these compounds was assessed against breast cancer cell lines [human breast adenocarcinoma (MCF-7)], which 7-Hydroxy-2-methyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ( 3f ) displayed the most cytotoxicity (IC₅₀=55.97 μg/mL), in contrast with Lapatinib (IC₅₀=79.38 μg/mL) as a known drug.     

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.     

Synthesis,Antimicrobial Activities,and Molecular Docking Studies of Dihydrotriazine Derivatives Bearing a Quinoline Moiety

In this article, three series of dihydrotriazine derivatives bearing a quinoline moiety ( 5a , 5b , 8a – 8c , and 9a – 9m ) have been designed, synthesized, and evaluated as antibacterial agents. Compounds 8a – 8c were found to be the most potent of all of the compounds tested with an MIC value of 1 μg/mL against several Gram‐positive (S. aureus 4220 and MRSA CCARM 3506) and Gram‐negative (E. coli 1924) strains of bacteria. In addition, 3‐[4‐amino‐6‐(phenethylamino)‐2,5‐dihydro‐1,3,5‐triazin‐2‐yl)‐6‐[(3‐chlorobenzyl)oxy]quinolin‐2‐ol ( 8a ) showed potent inhibitory activity (MIC=2 μg/mL) against Pseudomonas aeruginosa 2742, indicating that its antibacterial spectrum is similar to those of the positive controls gatifloxacin and moxifloxacin. Structure‐activity relationships (SAR) analyses and docking studies implicated the dihydrotriazine group in increasing the antimicrobial potency of the quinoline compounds. In vitro enzyme study implied that compound 8a also displayed DHFR inhibition.     

Aureonitols A and B,Two New C13‐Polyketides from Chaetomium globosum,an Endophytic Fungus in Salvia miltiorrhiza

Two new C₁₃‐polyketides, aureonitols A and B ( 1 and 2 ), along with five known compounds ( 3 – 7 ), were isolated from the solid fermentation culture of the plant endophytic fungus Chaetomium globosum from the aerial parts of Salvia miltiorrhiza. The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic data analysis and computed methods. Compound 5 was found to display the remarkable antimicrobial activities against four multidrug‐resistant bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis) with MIC values of 3.13–6.25 μg/mL (ciprofloxacin: 0.78–1.56 μg/mL), and also against all tested fungal strains with MIC values of 3.13–25 μg/mL (ketoconazole: 0.78–12.50 μg/mL).     

New Benzopyrrole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

A series of twenty compounds ( 23 – 42 ) were synthesized and characterized by spectral studies in order to explore newer antimicrobial compounds. The majority of the synthesized compounds reported significant antimicrobial properties against various pathogenic bacterial and fungal strains with the help of tube dilution method. Significant activities (MIC ranging from 3.9 to 15.62 μg/ml) have been shown against Gram-negative and Gram-positive bacteria with. In contrast, moderate to outstanding antibacterial activity was reported versus Gram-negative bacteria such as E. coli and P. aeruginosa along with Gram-positive bacteria such as S. aureus and B. subtilis. While antifungal activity was moderate to excellent against two fungus strains (Candida tropicalis, Candida glabrata). Compounds 25 and 34 had the utmost activity versus Gram-positive and Gram-negative bacteria too. The antifungal activity of compound 35 was comparable to that of standard. In-silico Molecular docking evaluations were performed for antibacterial and antifungal activities against the target DNA gyrase A (PDB: 1AB4) and 14 alpha-sterol demethylase enzyme (PDB: 1EA1), respectively. The dock score for typicals compounds for antibacterial and antifungal activity were −4.733 and −9.4, respectively. The three-dimensional QSAR examination was carried out by multiple linear regression (SA-MLR) with good predictive power (r2=0.9105, q2=0.8011). Establishment of several interactions between the ligand 25 and 34 and the active site of residue of both receptors, enable the ligand 25 and 34 to be fit well in the pocket of the active site, as seen in Molecular dynamics simulations analysis. Thus, data suggest that these ligands could be further explored as potential precursors to develop antimicrobial drugs.     

Antimicrobial activity of the extracts from fruits of <Emphasis Type="Italic">Rumex</Emphasis> L. species

This study was designed primarily to investigate the antibacterial and antifungal activity of the extracts from fruits of six Rumex L. species: R. acetosa L., R. acetosella L., R. confertus Willd., R. crispus L., R. hydrolapathum Huds. and R. obtusifolius L. The 7 Grampositive and 7 Gram-negative bacteria strains and 5 fungal ones were tested by agar and broth dilution method. Determination of minimal inhibitory concentration (MIC) revealed that the extracts from R. confertus, R. crispus, R. hydrolapathum and R. obtusifolius exerted differential inhibitory effect on the growth of Gram-positive bacteria — staphylococci (MIC=62.5–125 μg/mL) and Gramnegative bacteria — Escherichia coli ATCC 3521, Proteus mirabilis, Pseudomonas aeruginosa (MIC=125→500 μg/mL); MIC values determined by agar dilution method were somewhat higher. The same extracts inhibited also the growth of fungi — Candida spp. or Trichophyton mentagrophytes ATCC 9533 (MIC=250–500 μg/mL), as found by agar dilution method. The total content of polyphenols (11.66–78.36 mg/g), anthracene derivatives (0.26–12.93 mg/g) and tannins (4.00–11.16%) was also determined.     

Dihydroisocoumarins and Phenylglycosides from Scorzonera longiana,Their Antimicrobial Activities and Molecular Docking Studies

Five new phenyl dihydroisocoumarin glycosides ( 1 – 5 ) and two known compounds ( 6 – 7 ) were identified from the butanol fraction of Scorzonera longiana. The structures of 1 – 7 were elucidated based on spectroscopic methods. Antimicrobial, antitubercular, and antifungal evaluation of compounds 1 – 7 were carried out using the microdilution method against nine microorganisms. Compound 1 was active only against Mycobacterium smegmatis (Ms) with a MIC value of 14.84 μg/mL. All tested compounds ( 1 – 7 ) were active against Ms but only compounds 3–7 were active against fungi (C. albicans, S. cerevisiae) with MIC values of 25.0–125 μg/mL. In addition, molecular docking studies were conducted against Ms DprE1 (PDB ID: 4F4Q), Mycobacterium tuberculosis (Mbt) DprE1 (PDB ID: 6HEZ), and arabinosyltransferase C (EmbC, PDB ID: 7BVE) enzymes. Compounds 2 , 5 , and 7 are the most effective Ms 4F4Q inhibitors. Compound 4 was the most promising inhibitory activity on Mbt DprE with the lowest binding energy of −9,9 kcal/mol.     

Design,Microwave‐Assisted Synthesis and in Vitro Antibacterial and Antifungal Activity of 2,5‐Disubstituted Benzimidazole

Seventeen novel 2,5‐disubstituted benzimidazole derivatives were designed, synthesized and evaluated for their antibacterial activities. The tested compounds B1 – B4 and C2 – C6 exhibited not only good antifungal activity but also favorable broad‐spectrum antibacterial activity. Also, the lowest MIC of antibacterial and antifungal activity was 2 μg/mL and 4 μg/mL, respectively. It suggested that the structure of compound including the different substituent and its sites directly affected the efficacy of the synthesized compounds.     

Synthesis and in vitro antimicrobial activity of new 4-phenyl-5-methyl-4H-1,2,4-triazole-3-thione derivatives

This study presents the synthesis, spectral analysis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole (5a–i) and 1,3,4-thiadiazole derivatives (9a, c, g, h). New compounds were obtained by cyclization reaction of acyl thiosemicarbazide derivatives in the presence of alkaline and acidic media. All synthesized compounds were screened for their in vitro antimicrobial activities. Nine of the compounds had potential activity against Gram-positive bacteria (MIC?=?3.91–500 µg/mL). Some compounds showed good activity especially against: Micrococcus luteus ATCC 10240 (MIC?=?3.91?31.25 µg/mL), Bacillus subtilis ATCC 6633 (MIC?=?15.63? 62.5 µg/mL), and Staphylococcus aureus ATCC 25923 (MIC?=?15.63?125 µg/mL).     

Antibacterial Diphenyl Ether,Benzophenone and Xanthone Derivatives from Aspergillus flavipes

The extract of the strain Aspergillus flavipes DL‐11 exerted antibacterial activities against six Gram‐positive bacteria. During the following bioassay‐guided separation, ten diphenyl ethers ( 1 – 10 ), two benzophenones ( 11 – 12 ), together with two xanthones ( 13 – 14 ) were isolated. Among them, 4′‐chloroasterric acid ( 1 ) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR‐ESI‐MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram‐positive bacteria with MIC values that ranged from 3.13 to 50 μg/mL, but none of the compounds exhibited activity against Gram‐negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100 μg/mL). In particular, the MICs of some compounds are at the level of positive control.     

Synthesis of a new class of antimicrobial agents incorporating the indolin-2-one moiety

New furanone derivatives incorporating the indolin-2-one moiety 3 were prepared via the Perkin reaction of isatins 1 with aroylpropionic acids 2 under conventional conditions or microwave irradiation. A series of functionally heterocyclic derivatives (e.g., pyridazines, pyrroles, and sulfonamides) incorporating the indolin-2-one moiety was achieved via reaction of 3 with different reagents under microwave irradiation conditions. The newly synthesized compounds were characterized on the basis of FTIR, ¹H, ¹³C NMR and mass spectral studies. Some of the new synthesized compounds were screened for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus), Gram-negative bacteria (Escherichia coli and Shigilla flexneri) and antifungal activity against Aspergillus flavus and Candida albicans. Compound 8 j was equipotent to chloramphenicol in inhibiting the growth of E. coli minimum inhibitory concentration (MIC 2.5 μg/mL). Compound 8j may possibly be used as a lead compound for developing a new antibacterial agents. The antibacterial activity is expressed as the corresponding MIC (μg/mL) values.     

Design,synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole

Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007?µg/mL). Moreover, compounds 7c–d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03–0.06?µg/mL and 0.06–0.12?µg/mL versus ampicillin 0.24?µg/mL and 0.12?µg/mL; respectively). Compounds 7a and 7c–d were highly potent against Escherichia coli (MIC, 0.49–0.98?µg/mL versus gentamycin 1.95?µg/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.     

Antimicrobial effects of the macrocyclic Cu(II)-tetraanhydroaminobenzaldehyde complex

The Cu(II)-tetraaza macrocyclic complex exhibited antimicrobial effects on bacteria, yeasts and filamentous fungi. The highest antibacterial activity was found withB. subtilis andS. aureus, the respective IC₅₀ values being 18 and 80 μg/L and the MIC values 50 and 1000 μg/L. A concentration of 1 mg/L exerted a bacteriocide effect onS. aureus. The MIC value forB. subtilis was 250 times lower and forP. aeruginosa 10 times lower than the corresponding values for ampicillin. The Cu-complex was inactive against all tested yeasts. The strongest antifungal effect was manifested forR. nigricans, with an IC₅₀ value under 0.1 mg/L, whereas inA. alternata the IC₅₀ was 13.5 mg/L.     

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles ( 15a – t and 16a – f ) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1–2 μg/mL) and 16d (MIC=0.5 μg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.     

Cyclohexenone Derivative and Drimane Sesquiterpenes from the Seagrass-Derived Fungus Aspergillus insuetus

One new cyclohexenone derivative ( 1 ), and two undescribed drimane sesquiterpenes ( 2 and 3 ), together with another seven known drimane sesquiterpenes were isolated from a seagrass-derived fungus Aspergillus insuetus SYSU6925. Structures of these metabolites were elucidated by comprehensive spectroscopic analysis, including NMR analysis, mass spectrometry, and ECD calculations. Compounds 1 – 3 , 5 and 7 displayed weak to moderate antifungal activities towards four phytopathogenic fungi, with Minimum inhibition concentration (MIC) values range from 50 to 200 μg/mL. Compound 1 , a rare cyclohexenone derivative with n-propyl group exhibited more potent inhibitory activities (MIC, 50 μg/mL) against F. oxysporum than positive control (Triadimefon). Compounds 2 and 3 also exhibit potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in RAW264.7 cells with IC₅₀ values of 21.5±1.1 and 32.6±1.16 μM, respectively.     

吸水链霉菌BS-112产生的抗真菌活性物质的分离纯化与结构鉴别

【目的】分离纯化吸水链霉菌(Streptomyces hygroscopicus)BS-112产生的抗真菌活性物质,究明各活性组分的结构,测定其对黄曲霉的抑制作用,为该菌株及其产生的抗真菌活性物质的应用提供依据。【方法】通过大孔吸附树脂柱层析、硅胶柱层析及制备HPLC等方法,对该菌株产生的抗真菌活性物质进行分离纯化;利用质谱(MS)和核磁共振谱(NMR)解析各活性组分的结构;采用微量液体稀释法测定各活性组分对黄曲霉的最小抑菌浓度(MIC)和最小杀菌浓度(MFC)。【结果】从BS-112菌株发酵液中分离获得4个抗真菌活性组分,利用波谱技术确定其结构分别为Tetrins A和B、Tetramycins A和B。96孔板法测得这4个化合物对黄曲霉的MIC分别为3.13μg/mL、12.56μg/mL、1.56μg/mL、6.25μg/mL,MFC分别为6.25μg/mL、25.0μg/mL、3.13μg/mL、12.56μg/mL。【结论】BS-112菌株产生的抗真菌活性物质由Tetrins A和B、Ttramycins A和B 4个化合物组成,它们对黄曲霉均具有良好的抑制作用。     

Design,synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents

A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precursor selenochroman-4-ones, the hybrid molecules in this study showed significant improvement in antifungal activities. Notably, compound B8 showed significant antifungal activity against other strains excluding Aspergillus fumigatus (0.25 μg/mL on Candida albicans, 2 μg/mL on Cryptococcus neoformans, 8 μg/mL on Candida zeylanoides and 2 μg/mL on fluconazole-sensitive strains of Candida albicans). Moreover, compounds B8, B9 and C2 also displayed most potent activities against four fluconazole-resistance strains. Especially the MIC values of the hybrid molecule B8 against fluconazole-resistant strains were in the range of 0.5–2 μg/mL. Therefore, the molecular hybridization approach in this study provided new ideas for the development of antifungal drug.     

Synthesis,biological evaluations and computational studies of N-(3-(-2-(7-Chloroquinolin-2-yl)vinyl) benzylidene)anilines as fungal biofilm inhibitors

In the present investigation, new chloroquinoline derivatives bearing vinyl benzylidene aniline substituents at 2nd position were synthesized and screed for biofilm inhibitory, antifungal and antibacterial activity. The result of biofilm inhibition of C. albicans suggested that compounds 5j (IC₅₀ value?=?51.2?μM) and 5a (IC₅₀ value?=?66.2?μM) possess promising antibiofilm inhibition when compared with the standard antifungal drug fluconazole (IC₅₀?=?40.0?μM). Two compounds 5a (MIC?=?94.2?μg/mL) and 5f (MIC?=?98.8?μg/mL) also exhibited good antifungal activity comparable to standard drug fluconazole (MIC?=?50.0?μg/mL). The antibacterial screening against four strains of bacteria viz. E. coli, P. aeruginosa, B. subtilis, and S. aureus suggested their potential antibacterial activity and especially all the compounds except 5g were found more active than the standard drug ciprofloxacin against B. subtilis. To further gain insights into the possible mechanism of these compounds in biofilm inhibition through the agglutinin like protein (Als), molecular docking and molecular dynamics simulation studies were carried out. Molecular modeling studies suggested the clear role in inhibition of this protein and the resulting biofilm inhibitory activity.     

Synthesis and in vitro microbiological evaluation of novel diethyl 6,6′-(1,4-phenylene)bis(4-aryl-2-oxo-cyclohex-3-enecarboxylates)

Novel bis cyclohexenone ester derivatives 14–19 were synthesized and characterized by their spectral data. In vitro microbiological evaluations were carried out for all the novel compounds 14–19 against clinically isolated bacterial and fungal strains. Compounds 15, 16, 18 against Staphylococcus aureus, 14, 15 against β-Haemolytic streptococcus, 15, 19 against Micrococcus luteus, 17, 18 against Salmonella typhii, 14, 17 against Shigella flexneri, 15 against Escherichia coli, 16 against Pseudomonas aeruginosa, 15, 18, 19 against Klebsiella pneumonia exhibited potent antibacterial activity at an minimum inhibitory concentration (MIC) value of 6.25 μg/ml, whereas compound 16 against Aspergillus flavus, 17 against A. niger, 16, 18 against Mucor indicus, 15, 17–19 against Microsporum gypseum revealed excellent antifungal activity at an MIC value of 6.25 μg/ml.