Mixed-ligand silver(I) complexes containing bis[2-(diphenylphosphino)phenyl]ether and pyridyl ligands

The reaction of [Ag₂(κ²-P,P′-DPEphos)₂(μ-OTf)₂] (1) (DPEphos = bis(2-(diphenylphosphino)phenyl]ether) with 1,10-phenanthroline (phen) and 4,4′-bipyridine in equimolar ratios afford, respectively, the mononuclear complex [Ag(κ²-P,P′-DPEphos)(phen)][OTf] (2) and the coordination polymer [Ag(κ²-P,P′-DPEphos)(μ-4,4′-bpy)]_n[OTf]_n (3). In complex 3, the silver atoms are bridged by 4,4′-bipyridine units to form a zigzag metallopolymer.     

Solid state and solution NMR, X-ray and antimicrobial studies of 1:1 and 2:1 complexes of silver(I) cyanide with alkanediamine ligands

Several complexes of AgCN with alkanediamine ligands (where the ligands are ethylenediamine, propane-1,3-diamine, butane-1,4-diamine, N,N′-dimethyl-ethylenediamine, N,N′-di-iso-propyl-ethylenediamine, etc.) have been synthesized and structurally characterized. In these species, alkanediamine ligands act as chelating ligands. The X-ray structure of the complex cyano-(N,N′-di-iso-propyl-ethylenediamine)-silver(I) was determined. These complexes have been also characterized by IR, solution as well as solid-state NMR studies. There are two types of IR absorptions observed for mono and dinuclear complexes. For the mono nuclear complexes, a sharp CN band is observed between 2111 and 2131 cm⁻¹ range, whereas for binuclear complexes the bands are in the range 2136-2140 cm⁻¹. The effect of the size of the ligands as well as their substituents is discussed. The antimicrobial activity studies of AgCN and its complexes show that the former exhibits substantial antibacterial activities compared to its complexes.     

Tyrosinase activity of Greyia flanaganii (Bolus) constituents

Hyper-pigmentation of the skin is a common problem that is prevalent in middle aged and elderly people. It is caused by over production of melanin. Tyrosinase is known to be the key enzyme in melanin production. Ethanolic extract of Greyia flanaganii leaves showed significant (P < 0.05) antityrosinase activity exhibiting the IC₅₀ of 32.62 μg/ml. The total extract was further investigated for its toxicity and effect on melanin production by melanocytes cells, and showed significant inhibition (P < 0.05) (20%) of melanin production at 6.25 μg/ml and low levels of cytotoxicity (IC₅₀ < 400 μg/ml). The amount of antioxidants necessary to decrease the initial DPPH absorbance by 50% (EC₅₀) by the total ethanolic extract was found to be 22.01 μg/ml. The effect of G. flanaganii against acne causing bacteria, Propionibacterium acnes, was investigated using microdilution assay. The MIC of the extract of G. flanaganii was found to be 250 μg/ml. Bioassay-guided fractionation led to the isolation of (3S)-4-hydroxyphenethyl 3-hydroxy-5-phenylpentanoate (1), 2′,4′,6′-trihydroxydihydrochalcone (2), 2′,6′,4-trihydroxy-4′-methoxydihydrochalcone (3), 2′,6′-dihydroxy-4′-methoxydihydrochalcone (4), 5,7-dihydroxyflavanone [(2S)-pinocembrin] (5), 2′,6′-dihydroxy-4′,4-dimethoxy dihydrochalcone (6) and (2R,3R)-3,5,7-trihydroxy-3-O-acetylflavanone (7). The isolated compounds were tested for their antioxidant, cytotoxicity, tyrosinase inhibition and antibacterial activities. Compound 2 exhibited significant (P < 0.05) antityrosinase activity exhibiting the IC₅₀ of 69.15 μM. The isolated compounds showed low toxicity of the cells with reduction of melanin content of the cells. All compounds tested showed good radical scavenging activity. These data indicates that G. flanaganii extract and its isolated phenolic constituents could be possible skin lightening agents.     

Cytotoxic benzil and coumestan derivatives from Tephrosia calophylla

A benzil, calophione A, 1-(6′-Hydroxy-1′,3′-benzodioxol-5′-yl)-2-(6″-hydroxy-2″-isopropenyl-2″,3″-dihydro-benzofuran-5″-yl)-ethane-1,2-dione and three coumestan derivatives, tephcalostan B, C and D were isolated from the roots of Tephrosia calophylla. Their structures were deduced from spectroscopic data, including 2D NMR ¹H-¹H COSY and ¹³C-¹H COSY experiments. Compounds were evaluated for cytotoxicity against RAW (mouse macrophage cells) and HT-29 (colon cancer cells) cancer cell lines and antiprotozoal activity against various parasitic protozoa. Calophione A exhibited significant cytotoxicity with IC₅₀ of 5.00 (RAW) and 2.90 μM (HT-29), respectively.     

Synthesis, characterization, and aqueous chemistry of cytotoxic Au(III) polypyridyl complexes

This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic [Au(polypyridyl)Cl₂]PF₆ complexes {(where polypyridyl = dipyrido[3,2-f:2′,3′-h] quinoxaline (DPQ), dipyrido[3,2-a:2′,3′-c] phenazine (DPPZ) and dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro) phenazine (DPQC))}. The crystal structure of [Au(DPQ)Cl₂]PF₆ was determined as example of the series and exhibits the anticipated square planar geometry common for d⁸ coordination complexes. The crystals of the complex belong to the space group P2₁/n with a = 7.624(2) Å, b = 18.274(5) Å, c = 14.411(14) Å, β = 98.03(3)°, and Z = 4. In ¹H NMR studies of these compounds in the presence of aqueous buffer, all four complexes rapidly converted to the dihydroxy species [Au(polypyridyl)(OH)₂] in a stepwise fashion. However, the [Au(polypyridyl)]³⁺ fragment believed to impart cytotoxicity in human ovarian cancer cell lines (A2780) remained intact and appeared stable for days. It was also noted that these Au(III) complexes were readily reduced in the presence of the common biological reducing agents, reduced glutathione and sodium ascorbate. How solution and redox stability may affect the biological activity of these novel Au(III) complexes is discussed.     

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.     

The structural definition of adducts of stoichiometry AgX:dppf (1:1)(n), X = simple anion, dppf = bis(diphenylphosphino)ferrocene

Single crystal X-ray structural characterizations are recorded for an array of adducts of the form AgX:dppf (1:1)_(n), X = simple (pseudo-)halide or oxy-anion, ‘dppf’ = bis(diphenyl phosphino)ferrocene, for adducts X = Cl (new phase), Br, I, SCN, OCN, CN, NO₃ (new phase), O₂CCH₃, n = 2, the form being dimeric [(dppf-P,P′)Ag(μ-X)₂Ag(P,P′-dppf)], for X = I, SCN, [Ag(μ-X)₂(P-dppf-P′)₂Ag′]; for X = O₂CCF₃, n = ∞, the form is an extended polymer: ?Ag(O · CO · CF₃)(P-dppf-P′)Ag′(O?. A dichloromethane solvate phase of CuI:dppf (1:1)₂ (also centrosymmetric) is also recorded. Synthetic procedures for all adducts have been reported. All compounds have been characterized both in solution (¹H, ¹³C, ³¹P NMR, ESI MS) and in the solid state (IR). The topology of the structures in the solid state was found to depend on the nature of the counterion.     

Acid phosphatase in Enteromorpha

Extracts of the alga Enteromorpha linza hydrolysed glucose-6-phosphate, p-nitrophenylphosphate 2′-, 3′-, and 5′-adenosine monophosphates with an optimum at pH 5. Cytidine and uridine-5′-nucleoside diphosphates, and 2′-, and 3′-adenosine monophosphates were relatively poorly hydrolysed. Zn²⁺ (10 mM) inhibited the hydrolysis of all substrates, whereas Mg²⁺ (10 mM) may be stimulatory. It is suggested that the hydrolysis of these phosphomonoesters was due to the activity of a non-specific acid phosphatase (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.2).     

Facile syntheses of BODIPY derivatives for fluorescent labeling of the 3' and 5' ends of RNAs

As inexpensive and readily available fluorophores for 3′ and 5′ end labeling of RNA molecules, symmetrical BODIPY (boron dipyrromethene: 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) derivatives having a primary amino group were designed, and their facile synthetic route was established. Novel BODIPY derivatives exhibited photophysical properties comparable to commercially available BODIPY FL EDA (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl ethylenediamine). To confirm utility of new derivatives, specific labeling of the 3′ and 5′ ends of in vitro transcribed RNAs was carried out. Furthermore, the 3′ end of the 5′ fragment of the bimolecular Tetrahymena ribozyme was labeled, and its catalytic activity was investigated.     

Peptidomimetic inhibitors of bacterial peptide deformylase

A series of N-formyl hydroxylamine peptide deformylase inhibitors containing a cyclic azaamino acid moiety between the P1′ and P3′ substituents are presented. Selected compounds display antibacterial activity against pathogens associated with respiratory tract infections with representative compounds showing excellent MICs against Haemophilus influenzae.     

Synthesis, structure and antitumor activity of [RhCl3(N-N)(DMSO)] polypyridyl complexes

The [RhCl₃(N-N)(DMSO)] complexes, the N-N being 2,2′-bipyridine (1), 1,10-phenanthroline (2), 4,7-diphenyl-1,10-phenanthroline (3), 4,4′-dimethyl-2,2′-bipyridine (4) and 1,10-phenanthroline-5,6-dione (5), have been synthesized and characterized with spectroscopic methods. The compounds 2-5 adopt mer- and complex 1fac-structure. The molecular and electronic structure studies of mer- and fac-complexes with bpy and phen ligands at the DFT B3LYP level with 3-21G^∗∗ basis set showed that mer-isomers are more stable. The cytostatic activity of the [RhCl₃(N-N)(DMSO)] complexes against Caco-2 and A549 tumor cells have been studied. Their antibacterial activity have also been investigated. It has been found that the very promising biological activity show complexes 2, 3 and 4.     

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.     

Synthesis,identification and in vitro biological evaluation of some novel quinoline incorporated 1,3-thiazinan-4-one derivatives

The present study describes the synthesis of two new series of 3-hydroxy-N-(4-oxo-2-phenyl-1,3-thiazinan-3-yl)-8-(trifluoromethyl)quinoline-2-carboxamide derivatives (4a–j) and 3-((7-chloroquinolin-4-ylamino)methyl)-2-phenyl-1,3-thiazinan-4-one derivatives (5a–7j). All the compounds were synthesized in moderate to good yield by one-pot three component cyclo-condensation reaction. The newly synthesized compounds were characterized by FT-IR, ¹H, ¹³C NMR and elemental analysis. The compounds were screened for their in vitro antibacterial activity against a panel of pathogenic bacterial strains, antitubercular activity against Mycobacterium tuberculosis H₃₇Rv and also for their in vitro antimalarial activity against Plasmodium falciparum. Among the synthesized compounds two of them (4f and 5f) showed excellent antibacterial activity against C. tetani at 15.6 μg/mL. Some of them exhibited excellent antitubercular (4f & 5f) and good antimalarial (4f, 5f & 6f) activity compared with the first line drugs.     

Design,Synthesis, Antioxidant and Antibacterial Activities of Novel 2-((1-Benzyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-Triazol-4-yl)methyl)-5-(2<Emphasis Type="Italic">H</Emphasis>Chromen- 3-yl)-2H-Tetrazoles

1,4-Disubstituted 1,2,3-triazole derivatives of 2H-chromene-3-tetrazoles synthesized regioselectively by copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click reaction were characterized by ¹HNMR, ¹³C NMR, IR, and mass spectral data. These derivatives were screened for in vitro antioxidant activity using DPPH radical, H₂O₂ scavenging, and iron chelating activity methods and also evaluated for in vitro antibacterial activities against E. coli and S. aureus bacterial strains. The MIC and IC₅₀ values for all these compounds were found to match the docking scores and relevant binding energies with the receptor active sites. These results allows one to consider the compounds as leads for a new generation of antioxidant and antibacterial agents.     

Purification of cofactor-dependent enzymes by affinity chromatography

Several 8-(6-aminohexyl)-amino adenine nucleotide derivatives, including ATP, 2′,5′-ADP, 3′,5′-ADP and desulfo-CoA (CoA, reduced coenzyme A), were prepared and immobilized on Sepharose by cyanogen bromide activation. 8-(6-Aminohexyl)-amino-ATP-Sepharose was found to exhibit good affinity for both NAD⁺-dependent dehydrogenases and kinases. Sequential biospecific elutions with NADH and ATP resulted in a good separation of dehydrogenases from kinases. As many as eight different dehydrogenases and kinases could be substantially purified from both porcine muscle and mouse kidney extracts by this new procedure. 8-(6-Aminohexyl)-amino-2′,5′-ADP- and −3′,5′-ADP-Sepharose were shown to exhibit good affinity for many NADP⁺-dependent dehydrogenases from yeast extracts and CoA-dependent enzymes, respectively. Purification of citrate synthases from pig heart and Eschericia coli extracts by means of these 8-substituted adenine nucleotide affinity columns was also presented.     

Enzymatic characteristics of two novel Myxococcus xanthus enzymes, PdeA and PdeB, displaying 3′,5′- and 2′,3′-cAMP phosphodiesterase, and phosphatase activities

Myxococcus xanthus PdeA and PdeB, enzymes homologous to class III 3′,5′-cyclic nucleotide phosphodiesterases, hydrolyzed 3′,5′- and 2′,3′-cyclic AMP (cAMP) to adenosine, and also demonstrated phosphatase activity toward nucleoside 5′-tri-, 5′-di-, 5′- and 3′-monophosphates with highest activities for nucleoside 5′-monophosphates. The substrate specificities of PdeA and PdeB show no similarity to that of any known cNMP phosphodiesterase, nucleotidase, or phosphatase. The enzyme activities of PdeA and PdeB were stimulated by 50 μM Mn²⁺ or Co²⁺. The K_m values of PdeA and PdeB for 3′,5′-cAMP, 2′,3′-cAMP, 5′-ATP, and 5′-AMP were in the low micromolar range (1.4-12.5  μM).     

Synthesis,crystal and antibacterial studies of diversely functionalized tetrahydropyridin-4-ol

In an effort to expand the spectrum of antibacterial activity associated with piperidin-4-one derivatives, we have synthesized two series of 3-carboxyethyl-2,6-diphenyl-4-hydroxy-Δ³-tetrahydropyridine derivatives bearing diversified heterocyclic and aromatic systems at the nitrogen atom through acetyl (6–18) and 2-propanoyl (9–31) linkers. Unlike acetyl derivatives, NMR spectral pattern of the propanoyl counterparts revealed the existence of pair of rotational isomers (syn and anti) in solution at room temperature due to the hindered rotation about N–CO bond. X-ray crystal studies of 9 and 24 clearly pointed out that all the compounds existed in only one form particularly, in stable syn form in solid state. Each of the compounds was screened for their in vitro antibacterial activity against nine human pathogenic Gram-positive strains including multiple drug resistant organisms and seven problematic Gram-negative strains. Among the various heterocycles examined here, imidazole substituted derivatives 12 and 25 exhibited antibacterial activity approaching that of Linezolid and Trovafloxacin drugs particularly against multiple resistant Enterococcus faecium-VanA phenotype strains.     

Phytochemical analysis and bioactivity assessment of five medicinal plants from Pakistan: Exploring polyphenol contents,antioxidant potential,and antibacterial activities

Plants have always been the prime focus in medicine industries due to their enormous ethnobotanical uses and multitude of biological and therapeutic properties. In the current study, preliminary phytochemical composition, Total phenolic content (TPC), and total flavonoid content (TFC) with the antioxidant and antibacterial activity of hydroalcoholic extract and n-hexane, chloroform and n-butanol fractions of five selected medicinal plants [Tephrosia purpurea (L.) Pers., Lavandula stoechas L., Aesculus indica (Wall. ex Cambess.) Hook, Iris ensata Thunb., and Kalanchoe pinnata (Lam.) Pers.] from Pakistan, have been evaluated. TPC and TFC were determined by Folin-Ciocalteu’s and AlCl₃ methods respectively. The antioxidant activity was performed by DPPH, ABTS, FRAP, and CUPRAC while the antibacterial potential of these plants was determined by agar well diffusion assay. K. pinnata (Lam.) Pers. exhibited the highest TPC (695 ± 13.2 mg.GA.Eq.g^-1DE ± SD) in n-butanol fraction and the highest TFC in its chloroform faction (615 ± 6.31 mg Q.Eq.g⁻¹ DE ± SD). The n-butanol fraction and hydroalcoholic extract of I. ensata Thunb. exhibited strong antioxidant potential by DPPH and CUPRAC assays respectively, whereas K. pinnata (Lam.) Pers. n-butanol fraction exhibited the strongest reducing potential. The hydroalcoholic extract of all tested plants exhibited significant antibacterial activity against tested bacterial strains with ZI (12–18 mm). Conclusively, K. pinnata (Lam.) Pers. (Family: Crassulaceae) and I. ensataThunb. (Family: Iridaceae) exhibited the highest antioxidant and antibacterial potential. They can be explored for the isolation of phytoconstituents responsible for this potential and serve as a lead for the production of new natural antioxidants and antibacterial agents that can be used to cure various diseases.     

Diaryl-1,2,4-oxadiazole antioxidants: Synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals

Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit ^·OH-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu²⁺/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS^+.) and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant.     

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.