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.     

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 and antimycobacterial evaluation of various 6-substituted pyrazolo[3,4-d]pyrimidine derivatives

Various pyrazolo[3,4-d]pyrimidines carrying a variety of substituents in the 6-position have been synthesised and their ability to inhibit growth of Mycobacterium tuberculosis in vitro has been determined. Compounds 5a, 5b, 6c, 7a, 7b, 8d, 8e and 8f demonstrated a minimum inhibitory concentration (MIC) of <6.25?µg/mL and were found to be active against Mycobacterium tuberculosis strain H₃₇RV. Compound 8d was found to be the most active compound in vitro with a MIC of <6.25?µg/mL and inhibitory concentration IC₉₀ of 1.53?µg/mL.     

A Silver Compound with Potential Applications as an Anticancer,Antibacterial, Antifungal,and Anti-Alzheimer's Agent

This study investigated the biological activity of the silver coordination compound K-22. The IC₅₀ values of K-22 on cancer cell lines range from 0.797 μg/mL to 3.426 μg/mL, indicating that K-22 might preferably inhibit A549, Saos-2, MCF-7, and HT-29 cell proliferation and thus have better therapeutic activity. Furthermore, K-22 stimulated apoptosis via up-regulation of the mRNA and protein expression level of Bax/Bcl-2 ratio in A549, Saos-2, MCF-7, and HT-29. K-22 exhibited antimicrobial activity against S. aureus, E. faecalis, K. pneumonia, P. aeruginosa, C. utilis, and C. albicans. Experimental results show that the compound has inhibitory potential with an IC₅₀ value of 178.10 μM for the BChE (butyrylcholinesterase) enzyme, which has a vital role in the progression of Alzheimer's disease. As a result, compound K-22 exhibits a strong potential for medical use due to its anticancer, antibacterial, antifungal, and anti-Alzheimer properties.     

Antimicrobial activities of Conyzolide and Conyzoflavone from Conyza canadensis

Antibacterial and antifungal activities of the two isolated compounds from Conyza canadensis have been reported in the current study. The two isolated compounds i.e. Conyzolide (1) and Conyzoflavone (2) were tested against six bacterial and five fungal strains, employing hole diffusion and macrodilution methods. Both the compounds showed significant activities against the tested pathogens with special reference to E. coli, P. aeruginosa, S. aureus, Trichophytom longifusus, C. albicans, and C. glaberata. Conyzolide revealed comparatively better antibacterial activity against E. coli (minimum inhibitory concentration (MIC): 25 µg/mL) in comparison to Conyzoflavone. However, in case of antifungal activities, Conyzoflavone exhibited superior antifungal activity against C. albicans (MIC: 10 µg/mL) as compared to Conyzolide.     

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).     

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).     

Susceptibility of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> strains toward combinations of oxacillin-2,4-dihydroxychalcone

In order to determine the existence of synergism of the bacteriostatic action of flavonoids against G⁺ bacteria between a clinically interesting conventional antibiotic and a flavonoid, combinations of oxacillin (OXC) and 2,4-dihydroxychalcone (DCH) as enhancer were assayed against methicillin-sensitive Staphylococcus aureus ATCC 29 213 and methicillin-resistant S. aureus ATCC 43 300. Using a kinetic-turbidimetric method, growth kinetics was monitored in a broth containing variable amounts of OXC alone and combinations of variable OXC-constant DCH. The minimum inhibitory concentrations (MIC) of OXC alone and in combination with DCH were evaluated. For the 29 213 strain, OXC MIC was 25 μg/mL, while combinations of 2–8 μg/mL OXC with 10 μg/mL of DCH totally inhibited growth and showed synergism. The resistance of the 43 300 strain in the presence of OXC was verified; OXC-DCH combinations decreased bacterial growth by 35 %. DCH augments the action of OXC against methicillin-susceptible S. aureus and therefore constitutes a good bacteriostatic agent for methicillin-resistant S. aureus.     

Two New Prenylated Indole Diterpenoids from Tolypocladium sp. and Their Antimicrobial Activities

Two new prenylated indole diterpenoids, tolypocladins K and L ( 1 and 2 ), together with a known analog terpendole L ( 3 ), were isolated from the solid fermentation culture of a mine soil‐derived fungus Tolypocladium sp. XL115. Their structures and relative configurations were determined by comprehensive spectroscopic data analysis, as well as by comparison of their NMR data with those related known compounds. Compound 3 exhibited remarkable antibacterial activity against Micrococcus luteus with an MIC value of 6.25 μg/mL, and compounds 1 and 3 displayed moderate antifungal activity selectively against tested strains with MIC values of 25–50 μg/mL.     

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.     

Dryoptkirbioside,A New Fructofuranoside Glycerol,and Other Constituents from Dryopteris kirbi Hook et Grav Rhizomes

A new fructofuranoside glycerol, dryoptkirbioside ( 1 ), along with thirteen known compounds ( 2 - 14 ), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAF_A fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC₅₀ values ranging from 4.0 to 8.8 μg/mL). Aspidinol P ( 5 ) and aspidinol B ( 6 ) exhibited moderate to low cytotoxicity on the three cell lines (IC₅₀ values ranging from 20.4 to 58.7 μM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4 μg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8 μg/mL). The main fractions EAF_B, EAF_C and nBF_B displayed excellent activity against S. aureus (MICs 11.7 and 23.4 μg/mL). Aspidinol B ( 6 ) had significant activity, while aspidinol P ( 5 ) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5 μM).     

Synthesis,Characterization, Antimicrobial and Antimalarial Activities of Azines Based Schiff Bases and their Pd(II) Complexes

Herein, we report synthesis, characterization, antimicrobial and antimalarial activities of azines Schiff base ligands (L¹−L⁴) and their palladium (II) complexes ( C¹−C⁴ ) of [Pd(L)(OAc)₂] type. The azine ligands (L¹−L⁴) were prepared by condensation of carbonyl compounds with hydrazine hydrate and their complexes by the reaction of palladium acetate with L¹−L⁴ ligands in 1 : 1 molar ratio. The prepared ligands and their complexes were characterized by spectral characterization using ¹H &¹³C-NMR, FT-IR and mass spectral studies, which revealed that the ligands coordinates via azomethine nitrogen and heteroatom or aryl carbon with palladium. Moreover, Schiff bases and their palladium (II) complexes have been screened for their antibacterial (S. aureus, B. subtillis, and S. typhi, P. aeruginosa), antifungal (C. albicans, A. niger, and A. clavatus) and antimalarial (P. falciparum) activities. The Schiff base L⁴ showed good results for antibacterial against S. aureus (MIC, 50 μg/mL) and antimalarial against P. falciparum (IC₅₀, 0.83 μg/mL). The complex C¹ showed best antibacterial activity (MIC, 62.5 μg/mL) against S. typhi and the complex C⁴ exhibited remarkable antimalarial activity (IC₅₀, 0.42 μg/mL) among the tested compounds. Thus, azines based ligands and their Pd complexes can be good antimicrobial and antimalarial agents if explored further.     

Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds

A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, 12 and 13 were demonstrated to have MICs of 0.0625 µg/mL against S. uberis in the presence of 50 µM ZnSO₄. Against S. aureus compounds 9g (MIC 4 µg/mL) and 11d (MIC 8 µg/mL) showed the greatest activity, whereas all compounds were found to be inactive against E. coli (MIC > 256 µg/mL); again in the presence of 50 µM ZnSO₄. All compounds were demonstrated to be significantly less active in the absence of supplementary zinc. Compound 9g was subsequently confirmed to be bactericidal, with an MBC (≥3log₁₀ cfu/mL reduction) of 0.125 µg/mL against S. uberis in the presence of 50 µM ZnSO₄. To validate the sanitising activity of compound 9g in the presence of supplementary zinc, a quantitative suspension disinfection (sanitizer) test was performed. In this preliminary test, sanitizing activity (>5log₁₀ reduction of CFU/mL in 5 min) was observed against S. uberis for compound 9g at concentrations as low as 1 mg/mL, validating the potential of this compound to function as a topical sanitizer against the major environmental mastitis-causing microorganism S. uberis.     

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.     

Synthesis,spectral characterization,and in vitro antibacterial and antifungal activities of novel 1,3-thiazine-2-amines comprising morpholine nucleus

A collection of 4-(4-morpholinophenyl)-6-aryl-6H-1,3-thiazin-2-amines (20–28) were synthesized and their in vitro antimicrobial activity was investigated. Compound 21 against P. aeruginosa, 23 against B. subtilis, 24 against V. cholerae and P. aeruginosa, 26 against S. aureus and B. subtilis, 27 against B. subtilis and E. coli, and 28 against all tested bacterial strains exerted excellent antibacterial activity. Compound 20 against A. flavus and Rhizopus, 21, 26 against Rhizopus, 22, 27 against Mucor, 23 against A. flavus, 24 against both A. flavus and Mucor, 25 against all tested strains, and 28 against Rhizopus and M. gypseum exerted excellent antifungal activity.     

Multi-targeted dihydrazones as potent biotherapeutics

Hydrazone compounds were considered as a useful moiety in drug design development. Therefore, these studies were aimed at the synthesis of new dihydrazones and were screened for their in vitro H⁺/K⁺-ATPase and anti-inflammatory activities. The results revealed that compounds 9 (22 ± 0.62 µg/mL), 10 (26 ± 0.91 µg/mL), 15 (24 ± 0.44 µg/mL), 16 (28 ± 0.63 µg/mL), 17 (12 ± 0.38 µg/mL), 18 (14 ± 0.47 µg/mL), 19 (26 ± 0.54 µg/mL), 20 (16 ± 0.41 µg/mL), 25 (06 ± 0.68 µg/mL) and 26 (08 ± 0.43 µg/mL) showed excellent H⁺/K⁺-ATPase activity and their IC₅₀ value were lower than the standard drug Omerazole (48 ± 0.12 µg/mL). Compounds 5 (28 ± 0.65 µg/mL), 6 (24 ± 0.61 µg/mL), 7 (28 ± 0.64 µg/mL), 8 (26 ± 0.45 µg/mL), 11 (30 ± 0.74 µg/mL), 12 (28 ± 0.40 µg/mL), 13 (32 ± 0.24 µg/mL), 14 (30 ± 0.55 µg/mL) and 21 (08 ± 0.47 µg/mL), 22 (12 ± 0.47 µg/mL), 23 (10 ± 0.51 µg/mL) and 24 (14 ± 0.84 µg/mL) showed better anti-inflammatory activity compared to standard indomethacin (44 ± 0.15 µg/mL). The structure activity relationship (SAR) showed that, electron donating groups (OH, OCH₃) favored the H⁺/K⁺-ATPase and antioxidants activity, whereas, electron withdrawing groups (F, Cl, Br and NO₂) favored the anti-inflammatory activity. Furthermore, molecular docking study was performed to investigate the binding interactions of the most active analogs with the active site of H⁺/K⁺-ATPase enzyme. Compounds 25 (G-score = −9.063) and 26 (G-score = −8.977) showed the highest docking G-scores for H⁺/K⁺-ATPase inhibition activity.     

Bioprospecting of the novel isolate Microbacterium proteolyticum LA2(R) from the rhizosphere of Rauwolfia serpentina

The study aimed to assess the proficiency of secondary metabolites (SMs) synthesized by actinobacteria isolated from the rhizospheric soil of Rauwolfia serpentina for its antimicrobial and anti-biofilm activity. After morphological and biochemical identification of actinobacteria, primary and secondary screening was done for specific metabolite production. The secondary metabolites were then tested for their antioxidant, antibacterial, and antibiofilm potential. Out of 29 bacterial colonies isolated, only one emerged as a novel isolate, Microbacterium LA2(R). Partial 16S rRNA gene sequence of the isolate LA2(R) was deposited in NCBI GenBank with accession number MN560041. The highest antioxidant capacity of the methanolic extract the novel isolate was found to be 474.183 µL AAE/mL and 319.037 µL AAE/mL by DPPH assay and ABTS assay respectively; three folds higher than the control. These results were further supported by the high total phenolic (194.95 gallic acid equivalents/mL) and flavonoid contents (332.79 µL quercetin equivalents/mL) of the methanolic extract. GC–MS analysis revealed the abundance of antibacterial compounds; where, n-Hexadecanoic acid was found to be the major compound present with a peak of 14 min retention time (RT) and 95% similarity index. MIC value of the metabolite was noted to be around 132.28 ± 84.48 μg/mL. The IC₅₀ value was found to be 74.37, 71.33, 66.28 and 84.48 μg/mL against Escherichia coli, Staphylococcus aureus, Klebsiella pneumonia, and Salmonella abony, respectively. Treatment with IC₅₀ of the extract decreased the biofilm formation up to 70%–80% against pathogenic strains viz. Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Salmonella abony. These significant activities of Microbacterium sp. LA2(R) suggests that it could be utilized for antibiotic production for human welfare and in various important industrial applications.     

Synthesis and antibacterial evaluation of novel 11-O-carbamoyl clarithromycin ketolides

A series of novel 11-O-carbamoyl clarithromycin ketolides were designed, synthesized and evaluated for their in vitro antibacterial activity. The results showed that the majority of the target compounds displayed improved activity compared with references against erythromycin-resistant S. pneumoniae A22072 expressing the mef gene, S. pneumoniae B1 expressing the erm gene and S. pneumoniae AB11 expressing the mef and erm genes. In particular, compounds 9, 18, 19 and 22 showed the most potent activity against erythromycin-resistant S. pneumoniae A22072 with the MIC values of 0.5 μg/mL. Furthermore, compounds 11, 18, 19, 24 and 29 were also found to exhibit favorable antibacterial activity against erythromycin-susceptible S. pyogenes with the MIC values of 0.125–1 μg/mL, and moderate activity against erythromycin-susceptible S. aureus ATCC25923 and B. subtilis ATCC9372.     

Synthesis of fluorinated carbazoles via C–H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities

An effective intramolecular C–H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)₂/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)₂ (0.5 mol %). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by ¹H, ¹³C and ¹⁹F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 μg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 μg/mL.     

Design,synthesis and antistaphylococcal activity of marine pyrrole alkaloid derivatives

Abstract

A novel set of 16 hybrids of bromopyrrole alkaloids with aroyl hydrazone were designed, synthesized and evaluated for antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA; ATCC 43866), methicillin-susceptible Staphylococcus aureus (MSSA; ATCC 35556) and Staphylococcus epidermidis (SE, S. epidermidis ATCC 35984). Of the 16 tested hybrids, 14 exhibited equal or superior antibiofilm activity against MSSA and MRSA relative to standard vancomycin. Compound 4m showed highest potency with antibiofilm activity of 0.39?µg/mL and 0.78?µg/mL against MSSA and MRSA, respectively. Thus, this compound could act as a potential lead for further development of new antistaphylococcal drugs.