Mycopyranone: A 8,8ˈ-binaphthopyranone with potent anti-MRSA activity from the fungus Phialemoniopsis sp.

A new 8,8?-binaphthopyranone (mycopyranone, 1) was isolated from a solid fermentation of Phialemoniopsis sp. (fungal strain MSX61662), and the structure was elucidated via analysis of the NMR and HRESIMS data. The axial chirality of 1 was determined to be M by ECD. The central chirality at C-4/C-4? was assigned through a modified Mosher’s method, while the absolute configuration at C-3/C-3? was deduced based on analysis of the ³J_H-3-H-4 values and NOESY correlations. Compound 1 was evaluated for its antimicrobial properties against Staphylococcus aureus SA1199 and a clinically relevant methicillin-resistant S. aureus strain (MRSA USA300 LAC strain AH1263). Compound 1 inhibited the growth of both strains in a concentration dependent manner with IC₅₀ values in the low μM range. Molecular docking indicated that compound 1 binds to the FtsZ (tubulin-like) protein in the same pocket as viriditoxin (2), suggesting that 1 targets bacterial cell division.     

Didemnaketals D and E,bioactive terpenoids from a Red Sea ascidian Didemnum species

Two new spiroketals, didemnaketals D (1) and E (2) were isolated from a marine ascidian species belonging to the genus Didemnum. The structures of the compounds were elucidated by extensive 1D (¹H, ¹³C, and DEPT) and 2D (COSY, TOCSY, HSQC, HMBC, NOESY, and ROESY) NMR studies and high-resolution mass spectroscopic data. The new didemnaketals differ from the reported ones in which that they lack the methyl functionality at C-6 and the hydroxy moiety at C-21. Instead, they possess an ester moiety at C-6 in addition to new oxygen functionality at C-20 of the didemnaketals. Compounds 1 and 2 were evaluated for their protein kinase inhibitory activity against different kinases (CDK5, CK1, DyrK1A, and GSK3) at 10 μg/mL. Compounds 1 and 2 showed moderate activity against these kinases. In addition, the compounds displayed moderate antimicrobial activity against Staphylococcus aureus and Bacillus subtilis, respectively.     

Anti-MRSA actinomycins D1-D4 from the marine sponge-associated Streptomyces sp. LHW52447

Actinomycins D₁?D₄ (1–4), four new D-type actinomycin analogues, were isolated from the fermentation broth of a strain of marine sponge-associated Streptomyces sp. LHW52447, together with actinomycin D (5). The structures of 1?4 were determined by a combination analysis of HRMS and NMR spectroscopic methods, and their absolute configurations of amino acids were determined by Marfey's analysis. Actinomycins D₁ (1) and D₂ (2) are the first two naturally occurring actinomycins with incorporation an oxazole unit into the central phenoxazinone chromophore. Both 1 and 2 showed more potent antibacterial activities against three strains of pathogenic methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 0.125–0.25?μg/mL than those of 3?5 with MIC values of 0.5–1.0?μg/mL, which suggested that the anti-MRSA activity might be enhanced by the incorporation of an additional oxazole unit. In addition, the cytotoxicity evaluation against WI-38 human diploid lung fibroblasts revealed that the incorporation of oxazole unit could decrease the cytotoxicity of actinomycins on human normal cells.     

Saxifraganoids A and B,two novel cucurbitane triterpenoid glycosides from Saxifraga umbellulata var. pectinata

Two novel cucurbitane triterpenoid glycosides, named saxifraganoids A (1) and B (2), were isolated from Saxifraga umbellulata var. pectinata. Their structures including absolute configurations were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HRMS), and single-crystal X-ray diffraction. Compound 1 represents the first example of cucurbitane triterpenoid with a Δ¹⁷⁽²⁰⁾, and compound 2 contained an unusual N-acetylglucosamine at C-16. The protective effects against liver injury induced by carbon tetrachloride (CCl₄) in the human embryonic-liver L-02 cells of these two compounds were evaluated.     

Synthesis,characterization and in vitro antimicrobial screening of quinoline nucleus containing 1,3,4-oxadiazole and 2-azetidinone derivatives

A series of 3-chloro-1-(aryl)-4-(2-(2-chloro-6-methylquinolin-3-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-4-ethyl-azetidin-2-ones (V)_1–12 have been synthesized and characterized by IR, ¹H NMR, ¹³C NMR and mass spectra. Synthesized compounds were screened for their antibacterial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes, while antifungal activity was determined against three different strains like Candida albicans, Aspergillus niger and Aspergillus clavatus. On the basis of statistical analysis, it has been observed that compounds gave significant co-relation.     

Microcalorimetric investigation of the antibacterial activity of curcumin on Staphylococcus aureus coupled with multivariate analysis

The antibacterial effect of Curcumin on Staphylococcus aureus growth was evaluated by microcalorimetry. The heat flow power?Ctime curves and nine quantitative parameters of the S. aureus growth were applied to investigate the inhibitory effect with Curcumin. By analyzing these curves and some quantitative parameters using multivariate analytical methods, similarity analysis and principal component analysis, the antibacterial activity of Curcumin on S. aureus could be accurately evaluated from the change of the two main parameters, the second exponential growth rate constant k ₂ and the maximum heat flow power P _m ² . The main two thermal parameters played more important role in the evaluation: at low concentration (0?C10.5???g?mL^?1), Curcumin hardly influence the growth of S. aureus, while at high concentration (10.5?C43.4???g?mL^?1) it could notably inhibit the growth. All these illustrated that the antibacterial activity of Curcumin on S. aureus was enhanced with the increase of the concentration of this compound. This study might provide an useful method and idea accurately evaluate the antibacterial effects of Curcumin, which provides some useful methods for evaluate the nature antibacterial agents.     

Isolation,structure elucidation,and antibacterial evaluation of the metabolites produced by the marine-sourced Streptomyces sp. ZZ820

New indole alkaloids streptoprenylindoles A–C (1–3) and diterpenoids 18-acetyl-cyclooctatin (8), 5,18-dedihydroxy-cyclooctatin (9), and 5-dehydroxy-cyclooctatin (10) were isolated from the culture of marine-derived Streptomyces sp. ZZ820, along with known 3-cyanomethyl-6-[3-methyl-2-butenyl]indole (4), N-(2-(1H-indol-3-yl)ethylacetamide (5), 1-acetyl-β-carboline (6), indole-3-methylethanoate (7), cyclooctatin (11), and chromomycin A₃ (12). Their structures were elucidated by a combination of extensive spectroscopic analyses, ECD calculation, and the Mosher's method. Streptoprenylindoles A (1) and B (2) are enantiomers that were separated through the preparation of their Mosher esters. Three new diterpenoids (8–10) showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli with MIC values of 24.11–55.12?μM, while chromomycin A₃ (12) showed potent antibacterial activities against MRSA (MIC: 0.59?μM) and E. coli (MIC 0.04?μM).     

Acylphloroglucinol derivatives from the twigs and leaves of Callistemon salignus

Three new acylphloroglucinol derivatives, callisalignones A–C (1–3), six new meroterpenoids, callisalignenes A–F (4–9), along with 18 known analogues (10–27) were isolated from the twigs and leaves of Callistemon salignus. Their structures and absolute configurations were established by comprehensive spectroscopic evidences (NMR, MS, amd electronic circular dichroism calculations). The absolute configurations of callistenones B (13) and H (14) were determined by comparison of their ECD spectra with that of callisalignone B (2). Callisalignones B and C are new adducts of β-triketone and acylphloroglucinol, whereas callisalignenes A–D are new meroterpenoids of acylphloroglucinol and α-phellandrene with different coupling models via hetero-Diels-Alder reaction, respectively. Myrtucommulone D (15) showed significant antibacterial activity against Staphylococcus aureus and three drug resistant S. aureus strains with MIC values of 1.953 and 0.975 μg/mL, respectively. Isomyrtucommulone B (17) displayed remarkable antibacterial activity against Escherichia coli with an MIC value of 0.122 μg/mL. Cytotoxic assay revealed that isomyrtucommulone B (17) was the most active against HCT116 with an IC₅₀ value of 2.09 ± 0.10 μM.     

In vitro biological studies of heteroleptic Ag(I) and Cu(I) unsymmetrical N,N′-diarylformamidine dithiocarbamate phosphine complexes; the effect of the metal center

A series of five dithiocarbamate and their respective Ag(I) and Cu(I) triphenylphosphine complexes of the general formula [Ag/Cu(PPh₃)₂L] were synthesized and characterized. The dithiocarbamate ligands were synthesized from formamidines with substituents in the 2 and/or 6 positions of the phenyl rings, intentionally keeping substituents on one ring different from those of the second phenyl ring while investigating the structure-activity relationship of Ag(I) and Cu(I) dithiocarbamate complexes. All Ag(I) and Cu(I) complexes with the general formula [Ag(PPh₃)₂L] (1–5) or [Cu(PPh₃)₂L] (6–10), displayed distorted tetrahedral geometry around the metal centers with coordination via two S atoms of the dithiocarbamate ligand and two P atoms from the PPh₃ units. Complexes 1–5 showed better inhibition values against Gram-positive, Staphylococcus aureus (methicillin resistant) and Staphylococcus aureus than the standard used, ciprofloxacin. Complexes 1 and 2 generally had good activity against all bacterial strains but were not active against Salmonella typhimurium. All Cu(I) complexes were either of low activity or inactive against all bacterial strains tested. Complex 2 was found to be more active with IC₅₀ values of 1.34 × 10⁻³ mM and 0.25 mM as agents for antioxidant activity against DPPH and NO free radical scavengers, respectively. The metal center played a vital role in their biological activity as the Ag(I) complexes displayed better antibacterial and antioxidant activity than Cu(I) complexes.     

Synthesis of novel ferrocene containing vic-dioxime ligands and their Ni(II), Cu(II) and Co(II) complexes: Spectral, electrochemical and biological activity studies

Two new vic-dioxime ligands bearing an important redox-active substituent, anti-β-ferrocenylethylaminoglyoxime (1a) and anti-β-ferrocenylethylaminophenylglyoxime (1b), have been synthesized, and their Ni(II), Cu(II) and Co(II) (2a-4a, 2b-4b) complexes were obtained. The composition and structure of the products were determined by elemental analysis, Fourier transform infrared (FT-IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), one-dimensional (1D) ¹H, ¹³C NMR, and two-dimensional (2D) heteronuclear multiple bond correlation (HMBC) techniques. The redox behaviors of the ligands and their complexes were investigated by cyclic voltammetry (CV), which revealed that all the ferrocenyl redox centers are electrochemically independent and undergo a quasi-reversible oxidation at similar potentials. Also, antibacterial activity was studied against Staphylococcus aureus ATCC 29213, Streptococcus mutans RSHM 676, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. The antimicrobial test results indicated that all the compounds have mild levels of antibacterial activity against both gram negative and gram-positive bacterial species.     

Vercytochalasins A and B: Two unprecedented biosynthetically related cytochalasins from the deep-sea-sourced endozoic fungus Curvularia verruculosa

Vercytochalasins A (1) and B (2), two biosynthetically related cytochalasins featuring novel structure and substituents, were isolated from the endozoic fungus Curvularia verruculosa which was associated with the deep-sea squat lobster Shinkaia crosnieri collected from the cold seep environment in South China sea. Their structures were elucidated by detailed interpretation of NMR spectroscopic and mass spectrometric data. The absolute configurations were confirmed by NOESY experiments as well as by DP4+ and ECD calculations. Differed from common cytochalasins, compound 1 is an uncommon secocytochalasin featuring the ester group cleaved between C-9 and C-23, and incorporating an additional oxygenated C4 unit which coupled with C-20 and C-22 to form a new substituted cyclohexenone moiety, while compound 2 contains an unusual 2?hydroxy-3-oxobutan-2-yl unit at C-22. Both compounds are distinctive from the commonly described cytochalasins. Compound 1 exhibited potent activity against angiotensin-I-converting enzyme (ACE) whereas compound 2 showed antibacterial activity. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with ACE.     

Ultrasonic-bath-assisted preparation of mononuclear copper(I) thiosemicarbazone complex particles: Crystal structure,characterization and antimicrobial activity

Particles of the copper(I) thiosemicarbazone complex [Cu(Brcatsc)(PPh3)2Cl]·CH3CN (1), Brcatsc = 2-bromo-3-phenylpropenalthiosemicarbazone, were synthesized by an ultrasonic-bath-assisted method and characterized by elemental analyses, NMR (¹H, ¹³C, and ³¹P) and FT-IR spectroscopies, X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The thermal stability of 1 was studied by thermal gravimetry analysis and its structure was determined by single crystal X-ray diffraction. The compound 1 is a mononuclear complex with the copper(I) ion coordinated in a distorted tetrahedral geometry by one S atom of Brcatsc, two P atoms of two PPh₃, and one Cl atom. The complex involves the Brcatsc thiosemicarbazone ligand in an S monodentate bonding mode. The antibacterial activity of the ligand and its copper(I) complex was studied against two gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria.     

Synthesis,studies and in vitro antibacterial activity of some 5-(thiophene-2-yl)-phenyl pyrazoline derivatives

In the present investigation, a novel series of pyrazolines 2a–2d were synthesized by the cyclization of various -1-[2-(alkoxy) phenyl]-3-(thiophen-2-yl) prop-2-en-1-one 1a–1d with N-substituted phenyl hydrazine and thiosemicarbazide in the presence of CH₃COOH and NaOH in ethanol which lead to the formation of new pyrazolines. The structures of these compounds were elucidated by, IR, ¹H-NMR, ¹³C-NMR, ESI-MS spectral data and their purities were confirmed by elemental analyes. The in vitro antibacterial activity of these compounds was evaluated against two Gram-positive and two Gram-negative bacteria Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus by microdilution method and then the minimum inhibitory concentration (MIC) of these compounds was determined. The results showed that compounds 1-[2-(benzyloxy) phenyl]-5-(thiophen-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl (2b) and 1-[2-(naphthalen-2-ylmethoxy) phenyl]-5-(thiophene-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazole-4-yl (2d) showed most promising antibacterial activity as compared to the antibiotics gentamicin and tetracycline in (Table 1, Table 2).     

New nitro-benzo[c]phenanthridine and indolopyridoquinazoline alkaloids from Zanthoxylum atchoum

The first phytochemical investigation of the roots of Zanthoxylum atchoum has led to the isolation of two new nitro-benzo[c]phenanthridine alkaloids 6-nitronitidine (1) and 6-nitro-8-methoxy-7,8-dihydronitidine (2), two new salts of indolopyridoquinazoline alkaloids 3-hydroxy-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (3) and its zwitterionic form 3-phenolate-8,13-dihydro-14-methyl-5-oxo-7H-indolo[2’,3’:3,4]pyrido[2,1-b]quinazolin-14-ium (4) along with 18 (5–22) known compounds. Their chemical structures were elucidated by spectroscopic analysis including 1D and 2D NMR and MS techniques. This is the first report of the nitro group on the biosynthesis of the natural benzo[c]phenantridine alkaloids. Compound 2 exhibited potent antibacterial activity against Staphylococcus aureus of MIC₅₀ = 4 μg·mL⁻¹.     

Synthesis and antimicrobial screening of 1,3,4-oxadiazole and clubbed thiophene derivatives

In the present study, a novel series of 2-{5-[4-(1-aza-2-(2-thienyl)vinyl)phenyl](1,3,4-oxadiazol-2-ylthio)}-N-arylacetamides (IV)_1–12 were synthesized and tested for their antimicrobial activity. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus. The chemical structures of newly synthesized compounds were elicited by IR, ¹H NMR, ¹³C NMR and mass spectral data. The synthesized bio-active compounds exhibited excellent to moderate antimicrobial activity. Compounds (IV)₅, (IV)₆ and (IV)₇ possess excellent antibacterial activity whereas compounds (IV)₆, (IV)₉ and (IV)₁₁ possess excellent antifungal activity.     

Synthesis and characterization of two new asymmetrical branched amines and related Mn(II) and Ni(II) Schiff base complexes containing pyridine moieties: Crystal structures of Mn(II) and Ni(II) complexes and their antibacterial properties

Two new branched pentadentate amines (N₅), 3,7-bis(2-pyridylmethyl)-5,5-dimethyl-3,7-diazaheptane-1-amine (1) and 4,8-bis(2-pyridylmethyl)-6,6-dimethyl-4,8-diaza octane-1-amine (2) have been prepared. These have been used to synthesis two new Schiff base complexes containing a pyridine and 2-pyridylmethyl pendant arm, by template [1+1] condensation of pyridine-2-carbaldehyde with the amines in the presence of Mn(II) in methanol. Elemental and spectral results are used to characterize the complexes and their structures are confirmed by single crystal X-ray diffraction studies. The structure of MnL¹(ClO₄)₂ indicates that in the solid state the Mn(II) ion adopts a slightly distorted octahedral geometry. The crystal structure of [Ni(1)(MeCN)](ClO₄)₂ is also reported and exhibits a slightly distorted octahedral geometry. Also the synthesized complexes were screened for their antibacterial activity against Escherichia coli (Lio), Serratia marcescens (PTCC 1330), Staphylococcous aureus (ATCC 6633), and Proteus vulgaris (Lio) and results showed that the all complexes have antibacterial effects and [NiL¹](ClO₄)₂, [MnL²](ClO₄) and [MnL¹](ClO₄)₂ have more effective ones against E. coli.     

Synthesis and antibacterial activity of four natural chalcones and their derivatives

Four natural chalcones bearing hydroxyisoprenyl or prenyl groups, named Paratocarpin E (2), Xanthoangelol D (3), Angusticornin A (4) and Kanzonol C (5), were prepared by employing the Claisen-Schmidt condensation as the key step. In an attempt to investigate the effect of the hydroxyisoprenyl group on biological activity, two of their derivatives were also prepared for antibacterial activity research. The synthesized compounds were investigated for their expected antibacterial activities against Gram positive bacteria (Bacillus subtilis, Staphylococcus aureus) as well as Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa). Paratocarpin E (2) was found to be the most potent against two Gram positive bacteria while the majority of the remaining compounds showed promising activity as well. However, all of the compounds were inactive against both Gram-negative bacteria.     

Synthesis,characterization, and biological activity of some complex combinations of nickel with α-ketoglutaric acid and 1-(o-tolyl)biguanide

The four divalent nickel complexes having α-ketoglutaric acid (H₂A) and 1-(o-tolyl)biguanide (TB) ligands have been synthesized, characterized, and tested for antibacterial and antitumor activity.The proposed formulas for these complexes are [Ni(TB)(HA)(H₂O)₂]Cl (C1), [Ni(TB)(HA)(H₂O)₂]Br (C2), [Ni(TB)(HA)]NO₃·H₂O (C3), and [Ni(TB)(HA)]CH₃COO (C4), where HA represents deprotonated H₂A.For the four complexes and for the ligands used in the synthesis, the antibacterial activity against Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 and antitumor activity in HeLa tumor cells were tested. A moderate cytotoxic effect of C3 and C4 complexes has been observed on the development and metabolic activity of HeLa cells, whereas C1 and C2 ligands have a very low effect on them.The synthesized complexes (obtained) inhibit adherence to the inert substrate of bacterial strains S. aureus and P. aeruginosa; therefore, they may be candidates for (potential) therapeutic applications.     

Chemical investigation of Cannabis sativa leading to the discovery of a prenylspirodinone with anti-microbial potential

The discovery of a new spiran based natural product, prenylspirodinone (1), together with six known cannabinoids (2–7) from the leaves of Cannabis sativa (Marijuana) is reported. All compounds were screened for antifungal and antibacterial activity against a panel of microbial pathogens and exhibited antimicrobial activities with IC₅₀ values ranging from 2.6 to 49.6?µM. Compound 2, a propyl substituted cannabidiol, was determined to be a specific inhibitor against C. albicans (IC₅₀ 11.9?µM) and can be considered as a new lead against Candidiasis.     

Synthesis, crystal structure and in vitro antibacterial activity of two novel silver(I) complexes

Two silver(I) complexes [Ag₂(dppm)₂(L¹)₂(CH₂Cl₂)₂] (1) and [Ag₄(dppm)₂(L²)₂(NO₃)₂] (2) have been prepared by the reactions of [Ag₂(dppm)₂(NO₃)₂] with HL¹ and HL² [dppm = bis(diphenylphosphino)methane, HL¹ = 2-(9H-carbazol-9-yl) acetic acid and HL² = (E)-3-(4-(9H-carbazole-9-yl) phenyl) acrylic acid], respectively. Both complexes have been structurally characterized by X-ray crystallography, confirming that 1 is a binuclear complex whereas 2 is a tetranuclear one. Both complexes were assayed for antibacterial activity against two Gram-positive bacterial strains (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC 13525 and Escherichia coli ATCC 35218) by MTT method. Complex 2 exhibited powerful antibacterial activities against B. subtilis ATCC 6633 with MIC of 0.78 μg/mL, which was superior to the positive controls penicillin G. On the basis of the biological results, structure-activity relationships were discussed.