Pancreatic lipase inhibitory activity of monogalactosyldiacylglycerols isolated from the freshwater microalga <Emphasis Type="Italic">Chlorella sorokiniana</Emphasis>

Chemical investigation of the freshwater microalga Chlorella sorokiniana led to the isolation of a monogalactosyldiacylglycerol (MGDG)-rich fraction possessing dose-dependent inhibitory activity against pancreatic lipase activity. The MGDG-rich fraction contains 12 MGDGs identified by LC/HRMS analysis. Among them, three MGDGs were new compounds, namely, (2S)-1-O-(7Z,10Z-hexadecadienoyl)-2-O-(7Z,10Z,13Z-hexadecatrienoyl)-3-O-β-D-galactopyranosylglycerol (1), (2S)-1-O-linoleoyl-2-O-(7Z,10Z-hexadecadienoyl)-3-O-β-D-galactopyranosylglycerol (6), and (2S)-1-O-oleoyl-2-O-(7Z,10Z-hexadecadienoyl)-3-O-β-D-galactopyranosylglycerol (8). The major galactolipids were isolated by semipreparative HPLC and tested for their effect toward pancreatic lipase inhibitory activity. All the tested MGDGs showed significant reduction of pancreatic lipase activity indicating possible beneficial use for management of lipase-related disorders such as obesity.     

Nematicidal metabolites from <Emphasis Type="Italic">Gliocladium roseum</Emphasis> YMF1.00133

A strain of the fungus Gliocladium roseum YMF1.00133 was found to secrete nematicidal metabolites against nematodes Panagrellus redivivus, Caenothabditis elegans and Bursaphelenchus xylophilus in experiments searching for nematicidal fungi. Through bioassay-guided fractionations, a unique trioxopiperazine alkaloid, gliocladin C (compound 1), and an alkylane resorcinol, 5-n-heneicosylresorcinol (compound 2) were obtained from the methanol extract of the fungus and determined by single-crystal X-ray analysis and spectroscopic data. In vitro immersion experiments showed that the ED₅₀ values of compounds 1 and 2 after 24 h incubation were 15 and 30 μg/mL against C. elegans, 50 and 80 μg/mL against P. redivivus, and 200 and 180 μg/mL against B. xylophilus, respectively. The X-ray diffraction data of compound 1 and the nematicidal activity of compounds 1 and 2 were reported for the first time.     

Bioactive phytochemicals from shoots and roots of <Emphasis Type="Italic">Salvia</Emphasis> species

The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (1–10), 1 sesquiterpenoid (11), 8 labdane (13–20), 15 ent-kaurane (21–35), 82 abietane, rearranged abietane and tanshinone (36–117), 3 icetexane (118–120), 43 clerodane (121–163), and 3 pimarane (164–166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167–169), 10 triterpenoids and β-sitosterol (170–180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181–201) including rosmarinic acid, flavonoids (202–217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219–221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.     

Antimicrobial Efficacy of Synthetic Pyranochromenones and (Coumarinyloxy)acetamides

Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls.     

Metabolomics-guided analysis of isocoumarin production by <Emphasis Type="Italic">Streptomyces</Emphasis> species MBT76 and biotransformation of flavonoids and phenylpropanoids

Introduction

Actinomycetes produce the majority of the antibiotics currently in clinical use. The efficiency of antibiotic production is affected by multiple factors such as nutrients, pH, temperature and growth phase. Finding the optimal harvesting time is crucial for successful isolation of the desired bioactive metabolites from actinomycetes, but for this conventional chemical analysis has limitations due to the metabolic complexity.

Objectives

This study explores the utility of NMR-based metabolomics for (1) optimizing fermentation time for the production of known and/or unknown bioactive compounds produced by actinomycetes; (2) elucidating the biosynthetic pathway for microbial natural products; and (3) facilitating the biotransformation of nature-abundant chemicals.

Method

The aqueous culture broth of actinomycete Streptomyces sp. MBT76 was harvested every 24 h for 5 days and each broth was extracted by ethyl acetate. The extracts were analyzed by ¹H NMR spectroscopy and the data were compared with principal component analysis (PCA) and orthogonal projection to latent structures (OPLS) analysis. Antimicrobial test were performed by agar diffusion assay.

Results

The secondary metabolites production by Streptomyces sp. MBT76 was growth phase-dependent. Isocoumarins (1–9), undecylprodiginine (10), streptorubin B (11), 1H-pyrrole-2-carboxamide (12), acetyltryptamine (13), and fervenulin (14) were identified, and their optimal production time was determined in crude extracts without tedious chromatographic fractionation. Of these compounds, 5,6,7,8-tetramethoxyl-3-methyl-isocoumarin (9) is as a novel compound, which was most likely synthesized by a type I iterative polyketide synthase (PKS) encoded by the icm gene cluster. Multivariate data analysis of the ¹H NMR spectra showed that acetyltryptamine (13) and tri-methoxylated isocoumarins (7 and 8) were the major determinants of antibiotic activity during later time points. The methoxylation was exploited to allow bioconversion of exogenously added genistein into a suite of methoxylated isoflavones (15–18). Methoxylation increased the antimicrobial efficacy of isocoumarins, but decreased that of the isoflavones.

Conclusion

Our results show the applicability of NMR-based metabolic profiling to streamline microbial biotransformation and to determine the optimal harvesting time of actinomycetes for antibiotic production.

     

Revision of the <Emphasis Type="Italic">Serrulati</Emphasis> species of <Emphasis Type="Italic">Penstemon</Emphasis> section <Emphasis Type="Italic">Saccanthera</Emphasis> subsection <Emphasis Type="Italic">Serrulati</Emphasis>

A revision of Penstemon sect. Saccanthera subsect. Serrulati includes a new species (P. salmonensis), a new variety (P. triphyllus var. infernalis), and the elevation of a subspecies to species (P. curtiflorus), bringing the total number of species to eight, which are keyed and described, complete with nomenclature and type citations.     

Design,synthesis, and characterization of 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate as a herbicidal and biological active agent

The present study was designed to synthesize the bioactive molecule 2,2-bis(2,4-dinitrophenyl)-2-(phosphonatomethylamino)acetate (1), having excellent applications in the field of plant protection as a herbicide. Structure of newly synthesized molecule 1 was confirmed by using the elemental analysis, mass spectrometric, NMR, UV-visible, and FTIR spectroscopic techniques. To obtain better structural insights of molecule 1, 3D molecular modeling was performed using the GAMESS programme. Microbial activities of 1 were checked against the pathogenic strains Aspergillus fumigatus (NCIM 902) and Salmonella typhimurium (NCIM 2501). Molecule 1 has shown excellent activities against fungal strain A. fumigates (35 μg/l) and bacterial strain S. typhimurium (25 μg/l). To check the medicinal significance of molecule 1, interactions with bovine serum albumin (BSA) protein were checked. The calculated value of binding constant of molecule 1–BSA complex was 1.4 × 10⁶ M^?1, which were similar to most effective drugs like salicylic acid. More significantly, as compared to herbicide glyphosate, molecule 1 has exhibited excellent herbicidal activities, in pre- and post-experiments on three weeds; barnyard grass (Echinochloa Crus), red spranglitop (Leptochloa filiformis), and yellow nuts (Cyperus Esculenfus). Further, effects of molecule 1 on plant growth-promoting rhizobacterial (PGPR) strains were checked. More interestingly, as compared to glyphosate, molecule 1 has shown least adverse effects on soil PGPR strains including the Rhizobium leguminosarum (NCIM 2749), Pseudomonas fluorescens (NCIM 5096), and Pseudomonas putida (NCIM 2847).     

Madurastatin B3, a rare aziridine derivative from actinomycete <Emphasis Type="Italic">Nocardiopsis</Emphasis> sp. LS150010 with potent anti-tuberculosis activity

Since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. To explore the potential of bioactive compounds from microbes isolated from the southeast of Tibet, China, a crude extract library was constructed and screened against Staphylococcus aureus. The strain Nocardiopsis sp. LS150010 was scaled up and subjected to further chemical studies, resulting in the identification of N-salicyloyl-2-aminopropan-1,3-diol (2) and its rare aziridine derivative, madurastatin B3 (1). Their structures were determined by detailed analysis of 1D, 2D NMR and HRMS data. Compounds 1 and 2 displayed significant inhibitory activity against S. aureus and methicillin resistant S. aureus, with MIC values of 6.25 µg/mL. Compound 1 also showed potent inhibitory activity against Bacillus subtilis and Escherichia coli, as well as activity in a Mycobacterium tuberculosis Bacillus Calmette-Guérin infected THP-1 cell model.     

Differential alkaloid profile in <Emphasis Type="Italic">Uncaria tomentosa</Emphasis> micropropagated plantlets and root cultures

The alkaloids of Uncaria tomentosa micropropagated plantlets and root cultures were isolated and identified by NMR and mass spectrometry. Plantlets yielded pteropodine (1), isopteropodine (2), mitraphylline (3), isomitraphylline (4), uncarine F (5), speciophylline (6), rhynchophylline (7) and isorhynchophylline (8). In plantlets growing under continuous light, tetracyclic alkaloids 7 and 8 decreased from 20 ± 1.8 at 2 months to 2.2 ± 0.33 mg/g dry wt at 6 months, while the pentacyclic alkaloids 1–4 increased from 7.7 ± 1.4 to 15 ± 0.05 mg/g dry wt, supporting their biogenetic conversion. Micropropagated plantlets produced four times more alkaloids (27.6 ± 3.1 mg/g dry wt) than greenhouse plants. Plantlet roots yielded 3, 4, 8 and the glucoindole alkaloids 3α-dihydrocadambine (9) and dolichantoside (10), the last one not previously found in Uncaria.     

An NADPH-dependent <Emphasis Type="Italic">Lactobacillus composti</Emphasis> short-chain dehydrogenase/reductase: characterization and application to (<Emphasis Type="Italic">R</Emphasis>)-1-phenylethanol synthesis

A new anti-Prelog short-chain dehydrogenase/reductase (SDR) encoding gene lcsdr was cloned from Lactobacillus composti DSM 18527, and heterologously expressed in Escherichia coli. LcSDR is nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and has a molecular weight of approximately 30 kDa. The optimal pH and temperature were 6.5 and 30?°C, respectively. The maximal reaction rate V_max was 133.9 U mg^?1; the Michaelis–Menten constant K _m of LcSDR were 0.345 mM for acetophenone (1a), and 0.085 mM for NADPH. Through introducing an EsGDH-catalyzed NADPH regeneration system, a biocatalytic process for (R)-1-phenylethanol ((R)-1b) was developed with outstanding time–space yield. Under the optimized conditions, 50 g l^?1 1a was converted to (R)-1b in 2 h with a yield of 93.8%, enantiomeric excess of product (e.e._p) above 99% and space–time yield of 562.8 g l^?1 d^?1.     

Highly enantioselective production of a chiral intermediate of sitagliptin by a novel isolate of <Emphasis Type="Italic">Pseudomonas pseudoalcaligenes</Emphasis>

Objective

To produce (S)-3-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one (S)-1 from 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-one (2) by microbial bioreduction.

Results

A new isolate of Pseudomonas pseudoalcaligenes reduced enantioselectively prochiral ketone 2 to chiral alcohol (S)-1. Whole cells of the bacterium were tolerant towards 20 % (v/v) DMSO and 10 g 2/l. Under the optimal conditions, the preparative-scale bioreduction yielded (S)-1 at 90 % yield and >99 % ee. Cells could be re-used with the yield and ee of product being 45 % and >99 %, respectively, after five cycles.

Conclusion

Bioreduction using whole cells of P. pseudoalcaligenes is an attractive approach to produce (S)-1, as a chiral intermediate of the anti-diabetic drug, sitagliptin.

     

Organic Solvent-Tolerant Marine Microorganisms as Catalysts for Kinetic Resolution of Cyclic β-Hydroxy Ketones

Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this report, we describe a straightforward approach to enantiomerically enriched (R)- and (S)-3-hydroxycyclopentanone 2a, (R)- and (S)-3-hydroxycyclohexanone 2b, and (R)- and (S)-3-hydroxycycloheptanone 2c involving a transesterification resolution of the racemates using whole cells of marine microorganisms as catalysts and vinyl acetate the acyl donor and solvent. Twenty-six strains from a wide collection of isolates from marine sediments were screened, and seven strains were found to markedly catalyze the resolution in an asymmetric fashion. Using the strain Serratia sp., (R)-2a was isolated in 27% yield with 92% ee and (S)-2a in 65% yield with 43% ee, corresponding to an E-value of 37; (R)-2b was isolated in 25% yield with 91% ee and (S)-2b in 67% yield with 39% ee, corresponding to an E-value of 40; and (R)-2c was isolated in 30% yield with 96% ee and (S)-2c in 63% yield with 63% ee, corresponding to an E-value of 75.     

2-(chromon-3-yl)imidazole derivatives as potential antimicrobial agents: synthesis,biological evaluation and molecular docking studies

A series of novel 2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (4a-h) were synthesized by one pot condensation of substituted 3-formylchromones (1a-h), benzil (2) and ammonium acetate (3) in refluxing acetic acid at 110 °C under N2 atmosphere. Allylation of compounds 4a-h with allyl bromide in the presence of fused K₂CO₃ furnished N-allyl-2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (6a-h). The synthesized compounds were characterized spectroscopically and evaluated for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains by disc diffusion method. Compounds bearing electron withdrawing substituents such as bromo (4f) showed significant inhibitory activity against S. cerevisiae (MIC 1.4 μg/ml) and 4g containing chloro substituent, displayed more inhibitory potential against C. albicans (MIC 1.5), as compared to the standard drugs. Compounds 6a and 4c exhibit remarkable inhibitory potential against B. subtilis with MIC 0.98 and 1.23, respectively. The time kill assay for active compound 6a was performed by viable cell count (VCC) method to elucidate the microbicidal nature of 2-(chromon-3-yl)imidazoles. A molecular docking study of most active compounds with target ‘lanosterol 14α-demethylase’ (CYP51) was performed to unravel the mode of antifungal action.     

Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L _OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L _OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L _OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L _imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L _OL 1)(CH₃CN)]PF₆ (CuL _OL 1), [Cu(I)(L _OL 2)(CH₃CN)]PF₆ (CuL _OL 2), [Cu(I)(L _OL 3)(CH₃CN)]PF₆ (CuL _OL 3), [Cu(I)(L _imz 1)(CH₃CN)₂]PF₆ (CuL _imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH₃CN)]PF₆ (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H₂) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL _OL 3 ≈ CuL _OL 1 > CuBIMZ > CuL _OL 2 > CuL _imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-l-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL _imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.     

New species of the Buprestid genus <Emphasis Type="Italic">Sphenoptera</Emphasis> Dejean from India and Pakistan with notes on the synonymy and nomenclature of some species of the subgenus <Emphasis Type="Italic">Sphenoptera</Emphasis> s. str. (Coleoptera,Buprestidae)

Sphenoptera (s. str.) galkae sp. n. from North Pakistan and. S. (s. str.) jacobsonorum sp. n. from India (Jammu and Kashmir State) are described and compared with closely related species. New synonymy is established for the following taxa: S. hypocrita Mannerheim, 1837 (= S. torrida Jakovlev, 1898; S. ixion Kerremans, 1912, synn. n.), S. bodemeyeri Jakovlev, 1900 (= S. quadrata Kerremans, 1909, syn. n.), S. exoleta Jakovlev, 1908 (= S. politipennis Obenberger, 1927, syn. n.), S. obruta Kerremans, 1909 (= S. chalcosoma Obenberger, 1927; S. abbreviata hetera Obenberger, 1927, synn. n.), S. tragacanthae (Klug, 1829) (= S. maledicta Obenberger, 1920; S. cilicica Obenberger, 1927; S. rambouseki Obenberger, 1927; S. klickai Obenberger, 1927; S. corrosa Obenberger, 1927; S. satrapa Obenberger, 1927; S. syriae Obenberger, 1927; S. vavrai Obenberger, 1927, synn. n.), S. magna Gory et Laporte, 1839 (= S. alexandri Obenberger, 1927, syn. n.). Lectotypes for 74 nominal species and subspecies are designated.     

New Taxa and Host Associations of the Weevil Subfamily Ceutorhynchinae (Coleoptera,Curculionidae) from Thailand

A new subgenus of Mecysmoderes Sch., Enzoellus Korotyaev, subgen. n. (type species Mecysmoderes carinatus Faust), two new genera of the tribe Hypohypurini Colonnelli, Siamohypurus Korotyaev, gen. n. (type species S. samuelsoni Korotyaev, sp. n.), Glikmanellus Korotyaev, gen. n. (type species G. rosti Korotyaev, sp. n.) and eleven new species of the weevil subfamily Ceutorhynchinae are described: Mecysmoderes (Memecyderes) sarukhanovi Korotyaev, sp. n. from Thailand, M. (Enzoellus) gressitti Korotyaev, sp. n. from Thailand and Laos, M. (Enzoellus) muratovi Korotyaev, sp. n., Megahypurus oroszi Korotyaev, sp. n., Cyphohypurus suppantschitschi Korotyaev, sp. n., Siamohypurus samuelsoni Korotyaev, sp. n., S. attilai Korotyaev, sp. n., Glikmanellus rosti Korotyaev, sp. n., all from Thailand; G. baloghi Korotyaev, sp. n. from Sri Lanka; G. obrieni Korotyaev, sp. n. and G. louisae Korotyaev, sp. n., both from India. A key to three species of Megahypurus from Thailand is given. Host plants are determined for Megahypurus alexandri Kor. and Glikmanellus rosti sp. n. from Koh Kood Island in southern Thailand, which were repeatedly collected from a tree of the family Rubiaceae.     

Endophytic <Emphasis Type="Italic">Bacillus megaterium</Emphasis> and exogenous stimuli affect the quinonemethide triterpenes production in adventitious roots of <Emphasis Type="Italic">Peritassa campestris</Emphasis> (Celastraceae)

The root bark of Peritassa campestris (Cambess.) A.C. Sm. (Celastraceae) accumulates quinonemethide triterpenes (QMTs), an important class of bioactive compounds that shows potent antitumor activity. The production of these metabolites is difficult by both chemical synthesis, because of the complex molecular structure, and extraction from plant resources, because of the low yield. Thus, the aim of this work was to evaluate the influence of some important factors on the synthesis of QMTs to increase their production in adventitious roots grown in vitro. The effects of luminosity, mechanical damage to the tissue, source and concentration of carbon, auxins, macronutrient and micronutrient concentrations and the elicitation with its endophytic microorganism, Bacillus megaterium, isolated from roots grown in vitro were evaluated. Additionally, we compared the production of QMTs of roots in vitro with that of P. campestris roots bark in natura. Our results showed that all stimulating agents affected the biosynthesis of QMTs, with the exception of luminosity. The pattern of QMTs produced was different for the in vitro and in natura roots, including the accumulation of the majority QMTs: the in vitro roots accumulated maytenin (1) and 22β-hydroxy-maytenin (2), and the in natura roots showed the accumulation of maytenin (1), 22β-hydroxy-maytenin (2), 20α-hydroxy-maytenin (3), and maytenol (4). Therefore, we concluded that the biosynthesis of QMTs by P. campestris roots is affected by biotic and abiotic factors.     

Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents

In this study, the N,N,O metal chelator 2-pyridinecarboxaldehydeisonicotinoyl hydrazone (HPCIH, 1) and its derivatives 2-acetylpyridine-(HAPIH 2), 2-pyridineformamide-(HPAmIH, 3) and pyrazineformamide-(HPzAmIH, 4) were employed in the synthesis of four copper(II) complexes, [Cu(HPCIH)Cl₂]·0.4H₂O (5), [Cu(HAPIH)Cl₂]·1.25H₂O (6), [Cu(HPAmIH)Cl₂]·H₂O (7) and [Cu(HPzAmIH)Cl₂]·1.25H₂O (8). The compounds were assayed for their action toward Mycobacterium tuberculosis H37Rv ATCC 27294 strain and the human tumor cell lines OVCAR-8 (ovarian cancer), SF-295 (glioblastoma multiforme) and HCT-116 (colon adenocarcinoma). All copper(II) complexes were more effective in reducing growth of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC₅₀ values (0.39–0.86 µM) are similar to those ones found for doxorubicin (0.23–0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively), as compared with isoniazid (MIC = 2.27 µM), which suggests the compounds are attractive candidates as antitubercular drugs.     

Three New Species of Dance Flies of the Subgenus <Emphasis Type="Italic">Empis</Emphasis> (<Emphasis Type="Italic">Polyblepharis</Emphasis>) (Diptera,Empididae) from Kazakhstan and Eastern Siberia

Three new species of dance flies (Diptera, Empididae) of the subgenus Polyblepharis Bezzi, 1909 of the genus Empis Linnaeus, 1758 are described and illustrated: E. (P.) bartakisp. n. (Kazakhstan), E. (P.) dulkeitisp. n. (Russia (Krasnoyarsk Territory)), and E. (P.) ozerovisp. n. (Kazakhstan).