Bioorganic Chemistry

The aim of this investigation was to synthesize a new series of 4-(1-oxo-isoindoline) and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxypropanolamines and test them for their β 1 -and β 2 -adrenergic receptor binding affinity in turkey erythrocyte membrane (β 1 ) and lung homogenate of rats (β 2 ). Phenoxypropanolamines with 1-oxo-isoindoline (12-16) and 5,6dimethoxy-1-oxo-isoindoline groups (17)(18)(19)(20) at the para position were synthesized by fusing phthalic anhydride/3,4-dimethoxyphthalic anhydride with para-aminophenol, followed by reaction with epichlorohydrin. Opening of the oxirane ring with various amines such as isopropylamine, tert-butylamine, homoveratrylamine and N-methylhomoveratrylamine gave the target compounds (12-20). The binding affinities of all the synthesized compounds were tested and compared with that of Propranolol 2 and atenolol. It was found that the incorporation of amidic functionality within the 1-oxo-isoindonline ring and 5,6-dimethoxy-1-oxo-isoindoline ring system lead to a high degree of cardioselectivity in the synthesized compounds similar to open chain phenoxypropanolamines. 1-oxo-isoindonline derivatives showed better affinity to β 1 adrenergic receptor, while the 5,6-dimethoxy-1-oxo-isoindoline derivatives generally showed better affinity to β 2 -adrenergic receptors. Two of the compounds 12 and 20 possessed β 1adrenergic receptor affinity comparable with that of atenolol and both showed a better cardioselectivity than atenolol. Both 12 and 20 are undergoing further pharmacological evaluation. β β β β-Adrenergic blocking agents / β β β β 1 -and β β β β 2 -adrenergic receptor binding affinity / atenolol /

Lignans are a group of compounds consisting of dimers of phenyl propane units. They are found in diverse forms distributed in a variety of plants. Sesame lignans in particular are obtained from Sesamum indicum, a highly prized oilseed crop cultivated widely in many countries in the east. The plant is the main source of clinically important antioxidant lignans such as sesamin, sesamolin, sesaminol and sesamol. These lignans exhibit antihypertensive, anticancerous and hypocholesterolemic activities as well especially in humans due to which they have become compounds of tremendous research interest in recent times. Sesamin is synthesized from shikimic acid through phenylpropanoid pathway and metabolised into enterolignans which play a pivotal role in protection against several hormone related diseases. In this paper we present an overview of current status of research on sesame lignans with respect to the analytical methods employed, the biological activities and biosynthesis of sesame lignans.

Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

F Magnetic resonance imaging High performance liquid chromatography coupled with Ultra Violet a b s t r a c t The paper describes ex vivo applications of colchicine derivatives for the treatment of human T-Lymphoblastoid (CEM) cells. Moreover, the role of the substitutions of ring A at C-1 and C-7 side chain of colchicine analogues was probed by the synthesis and examination of their effects on the three-dimensional (3-D) CEM cells' growth. The CEM cells were cultured in the hollow fiber bioreactor (HFB) device. We used 1 H and 19 F magnetic resonance imaging (MRI) to monitor changes in 3-D CEM cell culture. 19 F MRI was used for visualization of the cellular uptake of new fluorine derivatives. Before and after treatment CEM cells profile was investigated with high performance liquid chromatography (HPLC-UV). Crown j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o o r g pounds used to the synthesis of colchicines derivatives were purchased from Sigma-Aldrich (Oakville, ON).

Vitamin D-binding protein (DBP) and albumin (ALB) are abundant serum proteins and both possess high-affinity binding for saturated and unsaturated fatty acids. However, certain differences exist. We surmised that in cases where serum albumin level is low, DBP presumably can act as a transporter of fatty acids. To explore this possibility we synthesized several alkylating derivatives of 14 C-palmitic acid to probe the fatty acid-binding pockets of DBP and ALB. We observed that N-ethyl-5-phenylisooxazolium-3 0 -sulfonate-ester (WRK-ester) of 14 C-palmitic acid specifically labeled DBP; but p-nitrophenyl-and N-hydroxysuccinimidyl-esters failed to do so. However, p-nitrophenyl ester of 14 C-palmitic acid specifically labeled bovine ALB, indicating that the micro-environment of the fatty acid-binding domains of DBP and ALB may be different; and DBP may not replace ALB as a transporter of fatty acids.

Four 6-aminopenicillanic acid moieties were grafted at either rim of calix[4]arene, giving 2 novel generations
of penicillin, which were named calixpenam. Antibiotic tests showed that they have amplied activity with respect to
the corresponding penams against 3 gram-positive nonpenicillinase-producing strains of Streptococcus.

This paper deals with an efficient preparation of 2-Chloromethyl pyridine intermediate useful for preparation of pyridinylmethyl sulphinyl benzimidazole especially Rabeprazole sodium. In the present study, we have demonstrated a shorter route of synthesis for 2-Chloromethyl pyridine intermediate and in situ condensation with 2-Mercaptobenzimidazole to get Rabeprazole. This strategy is extremely advantageous from the commercial scale up point and would help in reducing the overall timeline and cost for the large scale manufacture of Rabeprazole sodium.

Pyridine-2,4,6-tricarbohydrazide Acarbose MMFF94X + Solvation a b s t r a c t A range of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4h) were synthesized and its biological inhibition towards aand b-glucosidases was studied. Most of the compounds demonstrate to be active against a-glucosidase, and quite inactive/completely inactive against b-glucosidase. A number of compounds were found to be more active against a-glucosidase than the reference compound acarbose (IC 50 38.25 ± 0.12 lM); being compound 4d with the p-hydroxy phenyl motive the most active (IC 50 20.24 ± 0.72 lM). Molecular modeling studies show the interactions of compound 4d with the active site of target a-glucosidase kinase.

Platinum-based heterogeneous catalysts are critical to many important commercial chemical processes, but their efficiency is extremely low on a per metal atom basis, because only the surface active-site atoms are used. Catalysts with single-atom dispersions are thus highly desirable to maximize atom efficiency, but making them is challenging. Here we report the synthesis of a single-atom catalyst that consists of only isolated single Pt atoms anchored to the surfaces of iron oxide nanocrystallites. This single-atom catalyst has extremely high atom efficiency and shows excellent stability and high activity for both CO oxidation and preferential oxidation of CO in H2. Density functional theory calculations show that the high catalytic activity correlates with the partially vacant 5d orbitals of the positively charged, high-valent Pt atoms, which help to reduce both the CO adsorption energy and the activation barriers for CO oxidation.

Currently, approximately 250 natural acetylenic epoxy structures are known. The present review
describes research concerning biologically active epoxy acetylenic lipids and related compounds isolated
from different sources. Intensive searches for new classes of pharmacologically potent agents produced
by living organisms have resulted in the discovery of dozens of such compounds that possess high anticancer,
cytotoxic, antibacterial, antiviral, and other activities. Acetylenic epoxides primarily belong to a
class of molecules containing triple bond(s) and epoxy group(s) belonging to different lipid classes
and/or other groups. This review emphasises natural and synthetic acetylenic epoxides and other related
compounds as important sources of leads for drug discovery. The present review is the first article
devoted to natural acetylenic epoxides.

The recent innovation strategy used in the modern agricultural biotechnology is an elaboration of new effective and ecologically safe plant growth regulating substances on the base of synthetic low molecular weight five and six-membered heterocyclic compounds derivatives of pyridine, pyrimidine, pyrazole, oxazole, and isoflavones as an effective substitutes of phytohormones and traditional plant growth regulators to develop agricultural crops with genetically improved commercially important traits such as accelerated growth and development, increased plant productivity and improved quality of production, and enhanced plant tolerance to abiotic stress factors such as drought, salinity, heat, chilling, osmotic stress, soil pollution by anthropogenic factors, and to biotic stress factors such as pathogens and pests [1]. Maize (Zea mays L.) is ancient cereal crop traditionally used as source for dietary food and pharmaceutical industry due to high content of nutrients such as lipids, proteins, carbohydrates, vitamins, dietary fiber and biological active compounds in the seed and seed oil, and as raw material for the biofuel industry and animal feed [2]. Our work was aimed to study of plant growth regulating activity of new synthetic low molecular weight heterocyclic compounds phosphorylated derivatives of oxazole and pyrimidine with perspective their application as a new effective substitutes of phytohormones for improving of cultivation of maize (Zea mays L.) hybrid Palmyra FAO 190. The conducted in the laboratory conditions researches showed high growth stimulating auxin-like effect of tested chemical compounds on germination of seeds, growth and development of maize seedlings during the vegetation. The comparative statistical analysis showed that the biometric indexes of 14th-day-old seedlings of maize grown on the water solution of heterocyclic compounds used at concentration 10-9M were higher than the biometric indexes of 21st-day-old seedlings of maize grown either on the distilled water (control) or on the water solution of auxins IAA and NAA used at the same concentration 10-9M in average: at the 23 % - by total length of seedlings, 5-37 % - by total length of roots, and at the 7-87 % - by total number of roots. The positive effect of some from tested chemical heterocyclic compounds on increase of synthesis of photosynthetic pigments in the leaves of 14th-day-old seedlings of maize was also found: the content of chlorophyll a was increased in average at the 5-10 %; the content of chlorophyll b was increased in average at the 10-74 %; the content of chlorophylls a+b was increased in average at the 5-11 %. The practical application in the agricultural biotechnology of synthetic low molecular weight heterocyclic compounds phosphorylated derivatives of oxazole and pyrimidine as new effective substitutes of phytohormones for improving of growth and development of maize (Zea mays L.) hybrid Palmyra FAO 190 was proposed.
1. V. Tsygankova, Y. Andrusevich, O. Shtompel, O. Myroljubov, A. Hurenko, R. Solomyanny, G. Mrug, M. Frasinyuk, O. Shablykin, V. Brovarets. Study of Auxin, Cytokinin and Gibberellin-like Activity of Heterocyclic Compounds Derivatives of Pyrimidine, Pyridine, Pyrazole and Isoflavones. European Journal of Biotechnology and Bioscience, 2016, 4(12): 29-44.
2. Shah T.R., Prasad K., Kumar P. Maize-A potential source of human nutrition and health: A review. Cogent Food & Agriculture. 2016, 2: 1166995.

La chromatographie sur Couche Mince (CCM) est une méthode qualitative qui a servi à identifier les phytoconstituants contenus dans les extraits aqueux de deux angiospermes Morinda mucida (ML) et Solanum aethiopicum (SA). Les résultats des tests pharmacologiques des extraits réalisés sur des lapins ont montré qu'ils induisent des hypotensions dose-dépendant. Toutefois, l'extrait de S. aethiopicum a présenté une efficacité plus accrue (DE50 = 3,31 mg/kg de PC.) Mots-clés : Étude chimique et pharmacologique, plantes anti hypertensives, CCM, Côte d'Ivoire. Abstract Thin layer chromatography (TLC) is a qualitative method that served to identify phytoconstituents contained in aqueous extracts of two angiosperms Morinda mucida (ML) and Solanum aethiopicum. The results of pharmacological tests of the extracts achieved on rabbits showed that they lead dose-dependent hypotensions. However, S. aethiopicum extract presented an efficiency more increased (DE50 = 3.31 mg/kg of b.w.)

A series of 2-deoxy-hexopyranosyl derivatives of uridine have been synthesized as analogues of UDPsugar. These compounds were tested as inhibitors against bovine b-1,4-galactosyltransferase I in fluorescent assays and showed no significant inhibition.

The condensation reaction of 5-(4-aminophenyl)-4-phenyl-1,2,4-triazole-3-thione with
salicylaldehyde, 4-hydroxybenzaldehyde, 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde,
2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde and 4-methoxybenzaldehyde
in methanol results in series of new Schiff bases. The structure of Schiff bases were confirmed
by
1H NMR, 13C NMR, IR and mass spectroscopy. The synthesized compounds were tested for
their antimicrobial activity against bacterial (Gram negative and Gram positive) strains in-vitro.
The synthetic compounds showed different inhibition zones against tested bacterial strains. All
compounds showed significant antiproliferative activity against Acinetobacter calcoaceticus
ATCC 23055. In detail, Entrococcus faecalis(Gram positive) was resistant to all prepared
compounds, whereas, A. calcoaceticus(Gram negative) was sensitive to all compounds
especially 5c, 5d and 4. S. aureus(Gram positive, relatively resistant to antimicrobials) showed
limited sensitivity to only 5c and 5d, and it was resistant to all other compounds and only 5c
exhibited low activity against P. aeruginosa(Gram negative). The best results belonged to 5c
that showed high activity against A. calcoaceticus(33 mm) as well as S. aureus(20 mm).

Maize (Zea mays L.) is an important crop for world agriculture. The elaboration of new effective growth regulators for intensification of maize growth and improvement of product quality is very actual problem. In this work impact of synthetic five and six-membered heterocyclic compounds derivatives of pyrimidine, pyrazole, isoflavones and phytohormones auxins IAA and NAA on germination of seeds and vegetative growth of maize was studied. Obtained data showed that treatment of maize seeds by heterocyclic compounds and auxins IAA and NAA used in concentrations ranging from 10-5 M to 10-13 M in water solution resulted in intensification of seed germination and increase of growth parameters of maize seedlings as compared to lower growth parameters of control untreated seedlings. Comparative statistical analysis showed that the biometric indexes of two-week maize seedlings grown on the water solution of heterocyclic compounds used in concentrations ranging from 10-9 M-10-10 M in water solution were as generally higher or similar to biometric indexes of maize seedlings grown on the water solution of auxins IAA and NAA used in the same concentrations as compared to lower biometric indexes of control maize seedlings grown on the distilled water (control). It was found that the highest growth stimulating activity showed compounds derivatives of isoflavones and pyrimidine, whereas derivatives of pyrazole showed lower stimulating activity. Obtained results indicate perspective of application of low molecular weight heterocyclic compounds derivatives of pyrimidine, pyrazole and isoflavones as new effective stimulators of seed germination and growth of maize seedlings.

Cyclin-dependent kinase RNA polymerase II Anti-tumour activity Induction of apoptosis Mcl-1 anti-apoptotic protein Drug discovery Cancer therapy a b s t r a c t A series of N-phenyl-imidazo [4,5-b]pyridin-2-amines, 4-indazolyl-N-phenylpyrimidin-2-amines and N-phenyl-4-pyrazolo[3,4-b]pyridin-pyrimidin-2-amines have been synthesized. Their anti-proliferative activities were tested in HCT-116 human colon carcinoma and MCF-7 breast carcinoma cell lines. Many exhibited potent anti-proliferative and CDK9 inhibitory activities. A lead compound 18b demonstrated the ability to reduce the level of Mcl-1 anti-apoptotic protein, to activate caspase 3/7 and induce cancer cell apoptosis. Propyl-1H-indazol-3-yl)ethanone (12, R 1 ¼ n-Pr) As bright yellow crystalline solid (4.72 g, 75%); 1 H NMR (DMSOd 6 ) d 0.85 (3H, t, CH 3 , J ¼ 7.2 Hz), 1.89 (2H, q, CH 2 , J ¼ 7.2 Hz), 2.61 (3H, s, CH 3 ), 4.46 (2H, t, CH 2 , J ¼ 7.2 Hz), 7.32 (1H, t, IndeH, J ¼ 7.6 Hz), 7.46 (1H, t, IndeH, J ¼ 7.6 Hz), 7.79 (1H, d, IndeH, J ¼ 8.4 Hz), 8.18 (1H, d, IndeH, J ¼ 8.0 Hz); HR-MS (m/z): calcd for C 12 H 14 N 2 O requires 202.1106; found 203.1392 [M þ 1] þ . 5.1.15. 1-(1-(Pyridin-3-ylmethyl)-1H-indazol-3-yl)ethanone (12, R 1 ¼ 3-methylpyridine) As a bright yellow crystalline solid (1.01 g, 64%); 1 H NMR (DMSOd 6 ) d 2.63 (3H, s, CH 3 ), 5.86 (2H, s, CH 2 ), 7.34 (1H, d, PyreH, J ¼ 6.4 Hz), 7.35 (1H, d, IndeH, J ¼ 7.6 Hz), 7.48 (1H, t, IndeH, J ¼ 8.0 Hz), 7.68 (1H, dt, PyreH, J ¼ 7.6, 1.6 Hz), 7.89 (1H, d, IndeH, J ¼ 8.4 Hz), 8.20 (1H, d, IndeH, J ¼ 8.4 Hz), 8.49 (1H, dd, PyreH, J ¼ 4.8, 1.6 Hz), 8.64 (1H, d, PyreH, J ¼ 2.0 Hz); HR-MS (m/z): calcd for C 15 H 13 N 3 O 251.1059; found 252.0645 [M þ 1] þ .

The one-step synthesis of nanodevices based on PAMAM framework for targeted cancer therapy is described. Four water-soluble nanodevices (named fractions F1 to F4) were rightly separated by size discrimination, and characterized. From biological assays of cell growth inhibition percentage, the anticancer activity of Methotrexate (chemotherapeutic drug) as part of a nanodevice, generally increases over cancer cell lines and notably, in case of human lymphocytes, the cell growth inhibition percentage decreases drastically (more than 80%), thus, the nanodevices exhibited a favorable discrimination between healthy and diseased cells. From the characterization it can be conclude that the synthesized nanodevices provide a dual scenario of drug transportation: encapsulation and conjugation.

The Ethno-medicinal studies have been carried out for the first time in Charmang, Tehsil Nawagai, district Bajaur, Khyber Pakhtunkhwa (KP), Pakistan. In this project a total of 64 medicinal plants belonging to 39 families and 58 genera and species have been documented, which are being used by the local communities for the treatment of different human sicknesses. Among 64 plant species, 58 medicinal plants species were found as compared with the 12 earlier published articles. This study mainly focused to protect the world's cultural tradition and to document the importance of medicinal plants present in the research area. A complete data has been established on the general and worldwide uses of the projected study to find out new possible species for further studies. A general field surveys was arranged in the desire area, which was based on semistructured meetings of 135 local sneaks. To assess the exact herbal knowledge, the data were investigated using quantifiable Ethno medicinal records as RFC (Relative Frequency Citation) and UV (Use Value), separately. The local interviewed peoples used 64 plant species belonging to 58 genera in 39 families, mainly Lamiaceae, Rhamnaceae and Solanaceae. The type of most common diseases (25%) was Respiratory diseases (Asthma, Throat infection, Cough etc.). The present study was emphasized based on ironic herbal knowledge to know the novel findings of medicinal plants in district Bajaur, KP, Pakistan which could be a standard use for upgrading the knowledge in terms of plant phytochemistry, pharmacology and biological activities for the efficiency and safety of medicinal plants.

Graphite oxide is one of the main precursors of graphene-based materials, which are highly promising for various technological applications because of their unusual electronic properties. Although epoxy and hydroxyl groups are widely accepted as its main functionalities, the complete structure of graphite oxide has remained elusive. By interpreting spectroscopic data in the context of the major functional groups believed to be present in graphite oxide, we now show evidence for the presence of five-and six-membered-ring lactols. On the basis of this chemical composition, we devised a complete reduction process through chemical conversion by sodium borohydride and sulfuric acid treatment, followed by thermal annealing. Only small amounts of impurities are present in the final product (less than 0.5 wt% of sulfur and nitrogen, compared with about 3 wt% with other chemical reductions). This method is particularly effective in the restoration of the p-conjugated structure, and leads to highly soluble and conductive graphene materials.

Circularly polarized light (CPL) emitted from star-forming regions is an attractive candidate as a cause of single chirality in nature. It has remained difficult, however, to translate the relatively small chemical effects observed on irradiation of molecular systems with CPL into high enantiomeric excesses. Here we demonstrate that irradiation of a racemic amino acid derivative with CPL leads to a small amount of chiral induction that can be amplified readily to give an enantiopure solid phase. A racemate composed of equal amounts of left-and right-handed crystals in contact with the irradiated solution is converted completely into crystals of single-handedness through abrasive grinding when racemization is effected in the solution. The rotation sense of the CPL fully determines the handedness of the final solid state. These findings illustrate the potential effectiveness of CPL in the control of molecular asymmetry, which is relevant for the origin of the single chirality inherent to many biological molecules.

In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa-g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC 50 ranging from 2.27 to 10.71 lM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.

A series of new a,b-unsaturated conjugated ketones containing ferrocenyl pyrazole unit were synthesized and fully characterized by IR and NMR spectroscopy. Electrochemical characterization of subject compounds was performed by means of cyclic voltametry. The in vitro cytotoxic activity of all the synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell growth inhibition of K562 cell lines in comparison with cisplatin as a reference compound.

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a derivative of the latter series elicited distinct responses in accordance with the dose. Thus, low concentrations (GI30) induced morphological changes characteristic of autophagic death with massive formation of cytoplasmic acid vacuoles without apparent loss of nuclear material, and with arrest of cell cycle at the G1 phase, whereas higher concentrations (GI70) induced apoptosis with arrest of cell cycle at the G1 phase.

In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a novel series of tricyclic pyrido[3 0 ,2 0 :4,5]thieno[3,2-d]pyrimidin-4-amine derivatives were designed and synthesized. These compounds were characterized by IR, 1 H NMR, 13 C NMR, elemental and mass spectral analyses. Docking studies have given a partial insight into the molecular determinants of the activity of this novel series in VEGFR-2 kinase active site. Moreover, these compounds were assessed at 10 lM for their selective inhibitory activities over a panel of 6 human kinases, namely VEGFR-1/Flt-1, VEGFR-2/KDR, EGFR, CDK5/p25, GSK3a and GSK3b. Compound N-(4,6-dimethylthieno[2,3-b]pyridine)-7,9-dimethylpyrido[3 0 ,2 0 :4,5]thieno[3,2-d]pyrimidin-4-amine (9d) exhibited the most potent and selective inhibitory activity against VEGFR-2/KDR over the six human kinases, with an IC 50 value 2.6 lM. The identification of this hit candidate could aid the design of new tricyclic-based VEGFR-2 kinase modulators.

A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC 50 < 9.3 mM) and compounds 13, 18 and 32 displayed moderate IC 50 values (25e40 mM).

A functionalized calixarene with four platinum(II) centers was synthesized as a potential anticancer
agent. The colorimetric cytotoxicity tests showed that it has amplified activity with respect to carboplatin against three different human carcinoma (non-small-cell lung, hepatocellular, and breast cancer) cell lines. It was most cytotoxic against the lung cancer cell line (IC50= 2.6μM).

The thiamin-diphosphate-dependent enzyme benzaldehyde lyase is a very import catalyst for chemoenzymatic synthesis catalyzing the formation and cleavage of (R)-hydroxy ketones. We have studied the stability of the recombinant enzyme and some enzyme variants with respect to pH, temperature, buffer salt, cofactors and organic cosolvents. Stability of BAL in chemoenzymatic synthesis requires the addition of cofactors to the buffer. Reaction temperature should not exceed 37 degrees C. The enzyme is stable between pH 6 and 8, with pH 8 being the pH-optimum of both the lyase and the ligase reaction. Potassium phosphate and Tris were identified as optimal reaction buffers and the addition of 20 vol% DMSO is useful to enhance both the solubility of aromatic substrates and products and the stability of BAL. The initial broad product range of BAL-catalyzed reactions has been enlarged to include highly substituted hydroxybutyrophenones and aliphatic acyloins.

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Reported here is a native chemical ligation strategy for the total chemical synthesis of the B1 domain of protein L. A synthetic construct of this 76 amino acid protein domain was prepared by the chemoselective ligation of two unprotected polypeptide fragments, one containing an N-terminal cysteine residue and one containing a C-terminal thioester moiety. The polypeptide fragments utilized in the ligation reaction were readily prepared by stepwise solid phase peptide synthesis (SPPS) methods for Boc-chemistry. The milligram quantities of protein required for conventional biophysical studies were readily accessible using the synthetic protocol described here. The folding properties of the synthetic protein L construct were also determined and found to be very similar to those of a similar wild-type protein L constructs prepared by recombinant-DNA methods. This work facilitates future unnatural amino acid mutagenesis experiments on this model protein system to further dissect the molecular basis of its folding and stability.

Study of plant growth regulating activity of synthetic low molecular weight heterocyclic compounds derivatives of pyrimidine, pyrazole, and oxazole was conducted. It was found that all tested synthetic heterocyclic compounds used at concentration 10-9 M/l of distilled water revealed high stimulating auxin-like activity on vegetative growth of two cultivars of pea and maize, and stimulating cytokinin-like activity on growth of the isolated cotyledons of pumpkin. The obtained biometric indexes of 21 st-day-old seedlings of pea (Pisum sativum L.) of cultivar L35/11 middle stalwart bewhiskered grown on the water solution of heterocyclic compounds used at concentration 10-9 M/l of distilled water were higher of the biometric indexes of 21 st-day-old seedlings of pea grown either on the distilled water (control) or on the water solution of auxins IAA and NAA used at the same concentration 10-9 M/l of distilled water in average: at the 7-8% - by total length of seedlings, at the 6-46%-by total length of roots, and at the 15-70% - by total number of roots. The obtained biometric indexes of 21 st-day-old seedlings of pea (Pisum sativum L.) of cultivar L303/04 semi-dwarf bewhiskered grown on the water solution of heterocyclic compounds used at concentration 10-9 M/l of distilled water were higher of the biometric indexes of 21 st-day-old seedlings of pea grown either on the distilled water (control) or on the water solution of auxins IAA and NAA used at the same concentration 10-9 M/l of distilled water in average: at the 18-23% - by total length of seedlings, at the 15-76% - by total length of roots, and at the 16-116% - by total number of roots. The obtained biometric indexes of 14 th-day-old seedlings of maize (Zea mays L.) hybrid Palmyra FAO 190 grown on the water solution of heterocyclic compounds used at concentration 10-9 M/l of distilled water were higher of the biometric indexes of 21 st-day-old seedlings of maize grown either on the distilled water (control) or on the water solution of auxins IAA and NAA used at the same concentration 10-9 M/l of distilled water in average: at the 23 % - by total length of seedlings, 5-37% - by total length of roots, and at the 7-87% - by total number of roots. The specific bioassay on cytokinin-like activity conducted on the 16 th-day-old cotyledons isolated from seeds of muscat pumpkin (Cucurbita moschata Duch. et Poir.) of cultivar Gilea, showed that all heterocyclic compounds derivatives of pyrimidine, pyrazole, and oxazole used at concentration 10-9 M/l of distilled water demonstrated high stimulating cytokinin-like activity. The indexes of biomass growth of isolated cotyledons of pumpkin grown on the water solution of heterocyclic compounds used at concentration 10-9 M/l of distilled water were higher of the indexes of biomass growth of isolated cotyledons of pumpkin grown either on the distilled water (control) or on the water solution of phytohormone cytokinin Kinetin used at the same concentration 10-9 M/l of distilled water in average at the 6-30%. It was shown also the positive effect of some from tested synthetic heterocyclic compounds derivatives of pyrimidine, pyrazole, and oxazole on activation of photosynthetic processes in the leaves of 21 st-day-old pea seedlings and 14 th-day-old maize seedlings due to increase of synthesis of photosynthetic pigments in the plant cells; the content of chlorophyll a was increased in average at the 4-36%; the content of chlorophyll b was increased in average at the 3-74%; the content of chlorophylls a+b was increased in average at the 5-36%; the chlorophylls a/b ratio was increased in average at the 3-44%; the content of carotenoids was increased in average at the 3-37% as compared with control, IAA and NAA, respectively; the carotenoid/chlorophyll ratio was increased in average at the 7-17% as compared with control. The application in agricultural biotechnology of synthetic low molecular weight heterocyclic compounds derivatives of pyrimidine, pyrazole, and oxazole as new effective substitutes of phytohormones auxins and cytokinins for improving of cultivation of pea, maize, and pumpkinis is proposed.

Cyclohexanone oxygenase (EC 1.14.13.-) produced by Acinetobacter NCIB 9871 is a flavin-containing NADPH-dependent monooxygenase that utilizes dioxygen to convert cyclic ketones into lactones. A variety of ketones were examined in order to determine the substrate specificity, regioselectivity, and enantioselectivity of cyclohexanone oxygenase. Lactones were synthesized using immobilized enzymes. The nicotinamide cofactor required by cyclohexanone oxygenase was regenerated in situ with glucose 6-phosphate and glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides.

Solar fuel production often starts with the energy from light being absorbed by an assembly of molecules; this electronic excitation is subsequently transferred to a suitable acceptor. For example, in photosynthesis, antenna complexes capture sunlight and direct the energy to reaction centres that then carry out the associated chemistry. In this Review, we describe the principles learned from studies of various natural antenna complexes and suggest how to elucidate strategies for designing light-harvesting systems. We envisage that such systems will be used for solar fuel production, to direct and regulate excitation energy flow using molecular organizations that facilitate feedback and control, or to transfer excitons over long distances. Also described are the notable properties of light-harvesting chromophores, spatial-energetic landscapes, the roles of excitonic states and quantum coherence, as well as how antennas are regulated and photoprotected.

Sugar is the central unit within a nucleotide connecting the DNA base with the phosphate group, which itself couples to the neighboring nucleotides within single-stranded DNA. The study of the excitation, ionization, and fragmentation of biomolecular systems is essential for the understanding of many problems in the area of life sciences such as the mechanism of radiation damage in cellular systems or the action of radiosensitisers used in tumor therapy.

Fluorescent molecular rotors belong to a group of twisted intramolecular charge transfer complexes (TICT) whose photophysical characteristics depend on their environment. In this study, the influence of solvent polarity and viscosity on several representative TICT compounds (three Coumarin derivatives, 4,4-dimethylaminobenzonitrile DMABN, 9-(dicyanovinyl)-julolidine DCVJ), was examined. While solvent polarity caused a bathochromic shift of peak emission in all compounds, this shift was lowest in the case of molecular rotors. Peak intensity was influenced strongly by solvent viscosity in DMABN and the molecular rotors, but polarity and viscosity influences cannot be separated with DMABN. Coumarins, on the other hand, did not show viscosity sensitivity. This study shows the unique suitability of molecular rotors as fluorescent viscosity sensors.