Terpenoids with potent antimycobacterial activity against Mycobacterium tuberculosis from Trigonostemon reidioides roots

Phytochemical investigation of Trigonostemon reidioides roots led to the isolation of fourteen compounds. These included six new diterpenoids, trigonoreidons A?F (1?6), together with eight known diterpenoids 7?14. The structures of the new compounds were elucidated by spectroscopic techniques and the absolute configuration at the asymmetric carbon was determined by the modified Mosher's method. The structure of trigonoreidon B (2) was confirmed by X-ray crystallographic analysis. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The isolated compounds were evaluated for antimycobacterial activity against Mycobacterium tuberculosis. Among the compounds that exhibited antimycobacterial activity, the diterpenoids rediocide C (12) and rediocide G (14) were the most active compounds, with the MIC value of 3.84 μM.     

The lipophilicity estimation of 5-arylidene derivatives of (2-thio)hydantoin with antimycobacterial activity

The lipophilicity of antituberculotic 5-arylidene derivatives of (thio)hydantoin, thioacetazone and isoniazid has been determined by reversed-phase thin-layer chromatography (RP-TLC). Mixtures of acetone and water (with acetone content 60-85%) were used as the mobile phase. The R(M) (relative lipophilicity) of each compound (except isoniazid) decreased linearly with the increasing concentration of acetone. The partition coefficients (log P) of the compounds were calculated by the use of eight computer programs (ClogP, KowWin, XlogP, AlogPs, CAChe, Pallas, Interactive analysis and Slipper) and compared with the experimental lipophilicity (R(M0)). According to the observations the best tools for in silico predicting log P of (2-thio)hydantoins are programs KowWin and AlogPs.     

A new bibenzyl derivative with nuclear factor-kappaB inhibitory activity from Schefflera arboricola (Araliaceae)

A new bibenzyl derivative (1), 4-acetoxy-3,5,3′,4′-tetramethoxybibenzyl, along with eight known compounds (2–9), was isolated from the twigs and leaves of Schefflera arboricola (Araliaceae). The isolated compounds were elucidated mainly by means of one-dimensional, two-dimensional NMR and MS, and by comparison with the literature data. Compounds 2–5 and 7–9 are first reported from this plant. In the in vitro assays, compound 1 displayed moderate nuclear factor-kappaB inhibitory activity.     

Rauvolfianine,a new antimycobacterial glyceroglycolipid and other constituents from Rauvolfia caffra. Sond (Apocynaceae)

The chemical investigation of the extract of the dried leaves of Rauvolfia caffra (Sond) (synonym Rauvolfia macrophylla) (Apocynaceae) led to isolation of a new glycoside derivative, rauvolfianine (1) as well as six known compounds: oleanolic acid (2), sitosterol-3-O-β-D-glucopyranoside (3), betulinic acid (4), vellosimine (5), sarpagine (6) and D-fructofuranosyl-β-(2→1)-α-D-glucopyranoside (7). Compounds 1, 2, 3, 4 and 7 were evaluated for antitubercular activity. Compounds 1 and 2 were the most active (MIC = 7.8125 and 31.25 μg/mL) towards the Isoniazid resistant strain of Mycobacterium tuberculosis AC45. Their structures and relative stereochemistry were elucidated by spectroscopic methods.     

Chemical Variability and In Vitro Anti-Inflammatory Activity of Leaf Essential Oil from Ivorian Isolona dewevrei (De Wild. & T. Durand) Engl. & Diels

The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and ¹³C-NMR, thus leading to the identification of 113 constituents (90.8–98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I−A was dominated by (Z)-β-ocimene, β-eudesmol, germacrene D and (E)-β-ocimene, while (10βH)-1β,8β-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-β-bergamotene were the main compounds of Subgroup I−B. The prevalent constituents of Subgroup II−A were germacrene B, (E)-β-caryophyllene, (5αH,10βMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II−B displayed germacrene B, germacrene D and (Z)-β-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III−A by (E)-β-caryophyllene, (10βH)-1β,8β-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III−B by (Z)-β-ocimene and (E)-β-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC₅₀ (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC₅₀ (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.     

Synthesis of Silver Nanoparticles from Extracts of Wild Ginger (Zingiber zerumbet) with Antibacterial Activity against Selective Multidrug Resistant Oral Bacteria

Antibiotic resistance rate is rising worldwide. Silver nanoparticles (AgNPs) are potent for fighting antimicrobial resistance (AMR), independently or synergistically. The purpose of this study was to prepare AgNPs using wild ginger extracts and to evaluate the antibacterial efficacy of these AgNPs against multidrug-resistant (MDR) Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis. AgNPs were synthesized using wild ginger extracts at room temperature through different parameters for optimization, i.e., pH and variable molar concentration. Synthesis of AgNPs was confirmed by UV/visible spectroscopy and further characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy analysis (EDXA), and Fourier-transform infrared spectroscopy (FTIR). Disc and agar well diffusion techniques were utilized to determine the in vitro antibacterial activity of plant extracts and AgNPs. The surface plasmon resonance peaks in absorption spectra for silver suspension showed the absorption maxima in the range of 400–420 nm. Functional biomolecules such as N–H, C–H, O–H, C–O, and C–O–C were present in Zingiber zerumbet (Z. zerumbet) (aqueous and organic extracts) responsible for the AgNP formation characterized by FTIR. The crystalline structure of ZZAE-AgCl-NPs and ZZEE-AgCl-NPs was displayed in the XRD analysis. SEM analysis revealed the surface morphology. The EDXA analysis also confirmed the element of silver. It was revealed that AgNPs were seemingly spherical in morphology. The biosynthesized AgNPs exhibited complete antibacterial activity against the tested MDR bacterial strains. This study indicates that AgNPs of wild ginger extracts exhibit potent antibacterial activity against MDR bacterial strains.     

Synthesis, Structure, and Antimicrobial Activity of Complexes of Pt(II), Pd(II), and Ni(II) with the Condensation Product of 2-(Diphenylphosphino)benzaldehyde and Semioxamazide

Summary. Complexes of Pt(II), Pd(II), and Ni(II) with the condensation derivative of 2-(diphenylphosphino)benzaldehyde and semioxamazide were synthesized, characterized, and their antimicrobial activity was evaluated. The ligand and the complexes were characterized by spectroscopic methods with the particular accent on NMR spectral analysis. For the palladium(II) complex, the crystal structure was determined by X-ray analysis. In all the complexes the ligand is coordinated as a tridentate via a P, N, O donor set. The Pd(II) and Pt(II) complexes have a square planar geometry, whereas the geometry of the Ni(II) complex is tetrahedral. The ligand showed antibacterial and antifungal activity, which was enhanced upon complexation.     

Synthesis,characterization and antimicrobial activity of Ni(II) and Zn(II) complexes with N′,N′-bis[(1E)-1-(2-pyridyl)ethylidene]propanedihydrazide. Crystal structures of two highly solvated bimetallic complexes of Ni(II)

The bimetallic [Ni₂(H₂L2)₂](ClO₄)₄ (1), [Ni₂(HL2)(H₂L2)](ClO₄)₃ (2) and [Zn₂(H₂L2)₂](BF₄)₄ (3) complexes (H₂L2 = N′,N′²-bis[(1E)-1-(2-pyridyl)ethylidene]propanedihydrazide) were synthesized and characterized. The structure of complexes (1) and (2) was established by X-ray analysis. NMR spectroscopy was used for the characterization of complex (3). The complexes (1) and (2) were obtained from the same synthetic reaction and two crystal types of these complexes have been isolated during the fractional crystallization process.     

Spectral,thermal and biological activity studies on ruthenium(II) complexes with some pyridylamines

Complexes resulted from the interaction of [Ph₃P]₃RuCl₂ with 2-aminoethylpyridine (aepy), 2-hydrazinopyridine (hzpy) and dipicolylamine (dpa) with KPF₆ have been isolated from ethanol. The structures of the complexes were investigated using elemental analyses, IR, magnetic moment, UV-Vis and ¹H NMR spectroscopy. The complexes have been isolated as [Ru(hzpy)₃](PF₆)₂, [Ru(hzpy)₂(aepy)](PF₆)₂, [Ru(hzpy)(aepy)₂](PF₆)₂, [Ru(dpa)₂](PF₆)₂ in an octahedral geometry. The thermal decomposition of complexes was discussed in terms of their structures and the thermodynamic parameters were evaluated. The metal complexes were screened for their antibacterial activity against bacterial species, Escherichia coli, Staphylococcus aureus, as well as fungus (Candida). The activity data show the metal complexes have potent antibacterials against one ore more bacterial species.     

噻吩甲酰三氟丙酮与萘胺的缩合反应、机理分析和抑菌活性

报道了噻吩甲酰三氟丙酮(TTA)与1-萘胺和2-萘胺缩合反应生成的TTA缩萘胺配体(TOBT-NA)及它们的铜(Ⅱ)、钴(Ⅱ)、镍(Ⅱ)和锌(Ⅱ)配合物．利用量子化学和分子力学计算方法对缩合反应的机理进行了探讨,较好地解释了TOBT-NA配体的烯胺酮式构型及其配合物的亚胺烯醇式构型．利用单片纸碟法测定了化合物的抑菌活性,为进一步研究结构和性能的关系提供了有益的参考．     

New samarium(III) complex of 5‐aminoorotic acid with antioxidant activity

A samarium(III) complex (SmAOA) of 5‐aminoorotic acid (HAOA) was synthesized by reaction of the respective inorganic salt and ligand in a molar ratio of 1:3. The structure of the complex was determined by means of elemental analysis and UV–visible, NMR, Fourier transform infrared (FT‐IR) and FT Raman spectroscopies. Significant differences in the FT‐IR and FT Raman spectra of the complex were observed as compared to the spectra of the free ligand. Detailed vibrational analysis of HAOA and Sm(III)–AOA systems revealed that the binding mode in the complex was bidentate through the carboxylic oxygen atoms. The newly synthesized SmAOA showed antioxidant properties. The antioxidant activities of both HAOA and SmAOA were related to their electron donor properties. Copyright © 2015 John Wiley & Sons, Ltd.     

One-step multiple component isolation from the oil of Crinitaria tatarica (Less.) Sojak by preparative capillary gas chromatography with characterization by spectroscopic and spectrometric techniques and evaluation of biological activity

Gas chromatographic analysis revealed that the oil of Crinitaria tatarica was rich in sabinene (32.1%), β-pinene (8.8%), and two unknown (M+200) compounds (I) and (II) (21.4% and 3.4%). One-step multiple fractionation of the oil and separation of two unknown constituents were performed using preparative capillary gas chromatography connected to preparative fraction collector system. This combination allowed separation and recover of sufficient quantities of two unknown compounds with high purity from complex oil matrix. Separation conditions (column temperature, cooling temperature, flow rate, injection volume, cut time) were optimized to achieve the best isolation and successful collection. The target compounds were separated from the oil using a HP Innowax (Walt & Jennings Scientific, Wilmington, DE, USA) preparative capillary column in rapid one-step manner with 95.0% purity. Trapping of the isolated compounds in collector system was facilitated by cooling with liquid nitrogen. Structure determination was accomplished by spectral analysis including ultraviolet, nuclear magnetic rezonance, and high-resolution electrospray ionization mass spectrometry. Z- (I) and E-artemidin (II) were isolated for the first time from this species. Crinitaria tatarica oil and Z- (I) and E-artemidin (II) were evaluated for biological activity.     

Identification of glucosyl-3-phosphoglycerate phosphatase as a novel drug target against resistant strain of Mycobacterium tuberculosis (XDR1219) by using comparative metabolic pathway approach

Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB). The resistance is as severe that it resulted in failure of the current chemotherapy regimens (i.e. anti-tubercular drugs). It is therefore imperative to discover the new anti-tuberculosis drug targets and their potential inhibitors. Current study has made the use of in silico approaches to perform the comparative metabolic pathway analysis of the MTBXDR1219 with the host i.e. H. sapiens. We identified several metabolic pathways which are unique to pathogen only. By performing subtractive genomic analysis 05 proteins as potential drug target are retrieved. This study suggested that the identified proteins are essential for the bacterial survival and non-homolog to the host proteins. Furthermore, we selected glucosyl-3-phosoglycerate phosphatase (GpgP, EC 5.4.2.1) out of the 05 proteins for molecular docking analysis and virtual screening. The protein is involved in the biosynthesis of methylglucose lipopolysaccharides (MGLPs) which regulate the biosynthesis of mycolic acid. Mycolic acid is the building block of the unique cell wall of the MTB which is responsible for the resistance and pathogenicity. A relatively larger library consisting of 10,431 compounds was screened using AutoDock Vina to predict the binding modes and to rank the potential inhibitors. No potent inhibitor against MTB GpgP has been reported yet, therefore ranking of compounds is performed by making a comparison with the substrate i.e. glucosyl-3-phosphoglycerate. The obtained results provide the understanding of underlying mechanism of interactions of ligands with protein. Follow up study will include the study of the Protein-Protein Interactions (PPIs), and to propose the potential inhibitors against them.     

Synthesis and biological activity of trinuclear seven-coordinated tin(IV) complexes derived from tridentate ligands and trimesic acid

The synthesis of trinuclear Sn(IV) complexes 5a–h – prepared in a one-pot reaction of 2-amino-4-R-phenol (R=H, Me, Cl, NO₂), 2-pyridine-carboxaldehyde, 1,3,5-benzenetricarboxylic acid (trimesic acid, H₃BTC), and dibutyl and dioctyltin oxides – is described. These compounds were characterized by elemental analysis, mass spectrometry, IR, and multinuclear NMR spectroscopy. The structures of 5a and 5b were also determined by single-crystal X-ray analysis. The trinuclear tin system is formed by bridges through the carboxylate moieties. The metal centers are seven-coordinate and the coordination polyhedron of tin can be depicted as distorted pentagonal-bipyramidal (PBP), where the equatorial plane consists of three oxygens and two nitrogens and the organic groups occupy the axial positions. The work presented here combines the useful properties of Schiff bases and H₃BTC ligands in the formation of organotin(IV) complexes, and investigates the likely antioxidant (DPPH and TBARS) and anti-inflammatory activity (TPA) of the new substances.     

Platinum(IV) complexes with purine analogs. Studies of molecular structure and antiproliferative activity in vitro

A series of tetrachloride platinum(IV) compounds of the general formulae PtCl₄L₂, where L = 1,2,4-triazolo[1,5-a]pyrimidine (tp) (1), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) (2), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) (3) and 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) (4) have been prepared and characterized by thermal analysis, ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR and IR spectroscopy. Spectral data suggest that the triazolopyrimidines act as a monodentate ligand via the nitrogen atom N(3). The preliminary assessments of antitumor properties of the four complexes were evaluated as in vitro antiproliferative activity against three cell lines: HL-60 human acute promyelocytic leukemia, SW707 rectal adenocarcinoma and HCV29T bladder cancer. PtCl₄(dbtp)₂ exhibits high cytotoxic activity against all human cell lines, whereas the other complexes are only moderately active.     

Co(III) complex with (E)-2-(2-(pyridine-2-ylmethylene)hydrazinyl)-4-(4-tolyl)-1,3-thiazole: structure and activity against 2-D and 3-D cancer cell models

Co(III) complex with a 2-hydrazonylthiazole ligand was synthesized and characterized by single-crystal X-ray diffraction. In the inner sphere of the complex, two monoionic ligands are coordinated tridentately forming octahedral geometry around Co(III). Activity of the complex was investigated on MCF-7 breast cancer cell line, with cisplatin (CDDP) as a reference compound. Results showed that after 24-h incubation, Co(III) complex revealed stronger cytotoxic activity compared to CDDP. Treatment of MCF-7 3-D cell model with the complex at 10 μM concentration achieved complete suppression of spheroid growth in almost the same extent as at 100 μM. In combination treatments on MCF-7 spheroids, the complex acted synergistically with CDDP, while additive interaction type was achieved when the complex was applied together with paclitaxel.     

In vitro anticancer activity of binuclear Ru(II) complexes with Schiff bases derived from 5-substituted salicylaldehyde and 2-aminopyridine with notably low IC50 values

The binuclear Ru(II) complexes with Schiff bases derived from 5-chlorosalicyladehyde and 2-aminopyridine and its 5-substituted salicylideneimine homologues were tested in vitro against cervical carcinoma (HeLa), metastatic colorectal adenocarcinoma (SW620), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), and human lung fibroblast (WI-38) cell lines. All compounds showed strong antiproliferative activity with extremely low IC₅₀ values. The compounds expressed strong activity against gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis.     

Synthesis,characterization and biological activity of Hg(II), Fe(III) complexes with 1,3,4-oxadiazole, 1,2,4-triazole derivatives from L-methionine

Four novel heterocyclic1,3,4-oxadiazole, 1,2,4-triazole derivatives, namely: 5-[1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazole-2(3H)-thione (4), 4-amino-5-[1-amino-3-(methylsulfanyl)propyl]-4H-1,2,4-triazole-3-thiol (5), 1-amino-3-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-5-thiol (7), and 5-[1-amino-3-(methylsulfanyl)propyl]-1H-1,2,4-triazole-3-thiol (9) have been synthesized from l-methionine and characterized by different spectroscopic techniques (FT-IR, UV–Vis, ¹H NMR, ¹³C NMR and MS). Complex formation with Hg⁺⁺ and Fe⁺⁺⁺ ions were formed from the four heterocyclic 4, 5, 7 and 9. The antimicrobial activities for synthetic intermediates and final four products were assisted using paper disk diffusion method against Gram-negative bacteria: Escherichia coli, Pseudomonas aeroginosae and Gram-positive bacteria: Staphylococus aureus 25923, Staphylococus aureus 43300 and showed variant activity against some of the microorganisms tested.     

Structural effects on the antitumour activity of a series of di(4-substituted phenyl)tin dichloride complexes with nitrogen-donor ligands

Investigation of the antitumour activity of a series of diorganotin dichloride complexes (4-ZC₆H₄)₂SnCl₂·L₂, where Z = OMe, Me, F, Cl, and CF₃ and L₂ = 2,2′-bipyridyl (bipy), 1,10-phenanthroline (phen) and 2-aminomethylpyridine (amp) is reported. A number of these complexex are shown to exhibit reproducible activity in vivo towards P388 lymphocytic leukaemia in mice. ¹H NMR data are reported for an extended series of (4-ZC₆H₄)₄Sn and the parent dichlorides (4-ZC₆H₄)₂SnCl₂ of the above-mentioned complexes. A correlation is reported between Hammett substituent constants and ¹H chemical shift data. Attempts are made to relate the antitumour activity of the complexes to various structural factors. The dependence of antitumour activity on the electronic effect of group Z and the nature of the ligand L₂ is demonstrated.