Synthesis and Herbicidal Activity of Phenoxypropionic Acid Derivatives with Imidazo[1,2-α]pyridine Moiety

Phenoxypropionic acid derivatives (Ia-s) with an imidazo[1,2-a]pyridine moiety were synthesized and their herbicidal activities were examined. The activities were affected dramatically by the substituents on the imidazo[1,2-a]pyridine ring, and good substituents to enhance the herbicidal activity were a cyano group at the 3-position and a chlorine atom at the 6-position. Among the compounds, n-propyl 2-[4-(6-chloro-3-cyano-2-imidazo[1,2-a]pyridinyloxy)phenoxy]propionate(Iq) was most active against gramineous weeds and the activity was comparable to that of the commercial herbicide fluazifop-butyl.     

Studies on Chemical Structure Modification and Structure?Activity Relationship of Derivatives of Gambogic Acid at C(39)

The natural product gambogic acid exhibits high potency in inhibiting cancer cell lines. Rational medicinal modifications on gambogic acid will improve its physicochemical properties and drug‐like characters. To investigate the structure? activity relationship of gambogic acid and also to find rational modification position on its chemical skeleton, we designed, synthesized, and characterized 16 derivatives of gambogic acid that were modified at C(39). The structure? activity relationships (SARs) were discussed. The anti‐proliferation data were accquired through MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assays of A549, BGC823, U251, HepG2, and MDA‐MB‐231 cancer cell lines. Most of the synthesized compounds showed strong inhibitory effects. The SAR study revealed that derivatives with aliphatic amino moieties at C(39) were more potent than those with other substituents. The C(39) position can undergo different kinds of chemical modifications without leading to loss of activity. Compounds 4 and 6 can serve as potential lead compounds for further development of new anticancer drugs.     

Studies on Chemical‐Structure Modification and Structure?Activity Relationship of Gambogic Acid Derivatives at Carbon(34)

Gambogic acid (GA), a natural product, was identified as a promising antitumor agent. To further explore the structure? activity relationship of GA and discover novel GA derivatives as antitumor agents, 19 novel GA derivatives modified at C(34) were synthesized and evaluated against A549, BGC‐823, U251, HepG2, and MB‐231 cancer cell lines by cellular assays. Among them, 15 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 3 possessed potent inhibitory activities against five cell lines with IC₅₀ values ranging between 0.24 and 1.09 μM . Compounds 9 and 18 were seven to eightfold more active than GA against A549 cell line. Chemical modification at C(34) of GA by introducing of hydrophilic aliphatic amines resulted in increased activity and improved drug‐like properties. These findings will enhance our understanding of the SAR of GA and can lead to the discovery of novel GA derivatives as potential antitumor agents.     

Structure–Activity Relationship of novel phenylacetic CXCR1 inhibitors

We reported recently the Structure–Activity Relationship (SAR) of a class of CXCL8 allosteric modulators. They invariably share a 2-arylpropionic moiety so far considered a key structural determinant of the biological activity. We show the results of recent SAR studies on a novel series of phenylacetic derivatives supported by a combined approach of mutagenesis experiments and conformational analysis. The results suggest novel insights on the fine role of the propionic/acetic chain in the modulation of CXCL8 receptors.     

Stereochemical Structure–Activity Relationship of N-(2,3-Epoxypropyl)-N-(α-methylbenzyl)benzenesulfonamide Derivatives

The absolute configurations of two asymmetric centers in four stereoisomers of N-(2,3-epoxypropyl)-N-(α-methylbenzyl)benzenesulfonamide were determined and their biological activities were tested. Consequently, N-[(R)-2,3-epoxypropyl]-N-[(R)-α-methylbenzyl]benzenesulfonamide was found to be the most active isomer and the stereochemistry of the benzyl position was found to be more important than that of C₂ in the epoxypropyl group for biological activity.     

Differential Response to the Herbicidal Activity of λ-Aminolevulinic Acid in Plants with High and Low Sod Activity

6-aminolevulinic acid (ALA) is the obligatory precursor for tetrapyrroles and for chlorophylls in plants. 1 Under illumination, these photosensitizers generate singlet oxygen, thus causing bleaching and death of treated tissues. We have examined whether superoxide is involved in the mode of action of ALA and whether SOD provides protection. Bean genotypes with similar carotenoid content but differing in SOD activity and cucumber seedlings were used throughout. Cucumber plants treated with 10 mM ethanolamine (EA) prior to ALA, had higher levels of chlorophyll fluorescence and lower values of electrolyte leakage than control. Bean cultivars with high SOD activity were considerably more tolerant to membrane damage caused by ALA than those with low SOD activity. SOD activity was greatly reduced in cucumber leaves treated with diethyldithiocarbamate (DDTC). Electrolyte leakage was markedly increased and chlorophyll fluorescence values were significantly lower in DDTC and ALA treated tissues as compared with those treated with ALA only. The results indicate that superoxide is involved in the toxicity caused by ALA and that, by breeding for high SOD activity. resistance to ALA can be achieved. thus allowing the use of ALA as a selective herbicide in the field.     

Synthesis,Antioxidant Activity,and Structure–Activity Relationship of SCAP1 Analogues

Nine analogues of antioxidant peptide SCAP1 were successfully synthesised using a solid-phase method on a 2-chlorotrytil resin. The compounds were obtained in a range of yields of 7.0–57.8%. The occurrence of aggregation during the synthesis is suspected to be responsible for the poor yields. All peptides were characterized by high-resolution time-of-flight mass spectrometry (HR-TOFMS) and nuclear magnetic resonance (NMR). The antioxidant activities of the SCAP1 analogues as well as SCAP1 were analysed utilising the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. The results revealed that all of the analysed peptides exhibited moderate antioxidant properties. Moreover, the evaluation of the structure–activity relationship showed that the Asn residue is an important requirement for the antioxidant activity of SCAP1. The replacement of Asn with other amino acid residues (Thr, Pro, Tyr, Trp and Phe) resulted in a decrease in the IC₅₀ values of the peptides. Notably, however, the replacement of the Lys residue with Val marginally increased the activity.

     

Structure Activity Relationship amongst Some Fungitoxic α-Naphthoquinones of Angiosperm Origin

Rubusoside, the β-D-glucosyl ester of 13-O-D-glucosyl-steviol which was isolated from leaves of Rubus suavissimus collected in China as the major sweet principle (yield: 5.4%), was subjected to α-1 4 transglucosylation with the cyclodextrin glucosyltransferase produced by Bacillus megaterium Strain No. 5 using soluble starch as a donor. A significant improvement in the quality of sweetness was observed for the crude reaction mixture, which was separated into mono-, di-, tri-, tetra-, penta-, and hexa-glucosylated products. All isomers of the mono- and di-glucosylated products were further separated. Evaluation of the sweetness of these products compared with stevioside, rebaudioside A, etc. disclosed that the ratio of the number of glucose units at the 13-hydroxyl group to that at 19-carboxyl group seems to have a significant relationship with the sweetness as well as the quality of taste for glucosides of this type.     

Relationship between Chemical Structure and Selectivity in Herbicidal Activity of trans-β-(2,4-Dichlorophenoxy)-acrylates against Rice Plant and Barnyard-grass

Twenty one esters of trans β-(2,4-dichlorophenoxy)acrylic acid were prepared and their inhibitory activity against shoot elongation in the rice plant and barnyard-grass was measured. The relationship between herbicidal activity and chemical structure was analysed using the Hansch approach. The selectivity (activity against barnyard-grass/activity against the rice plant) was mainly due to the lipophilic property of the esters between the two plant species.     

Chemical studies on malformin—III. : Structure of malformin A

The amino acid sequence of malformin A, cyclo-l-isoleucyl-d-cysteinyl-l-valyl-d-cysteinyl-d-leucyl, was confirmed. The presence of an SS bond in the molecule was proved by iodine oxidation of thiolmalformin A to malformin A. A stereoisomer, isomalformin A, was also produced during oxidation. Both SS compounds were interconvertible via the SH compound. Possible steric configurations of malformin A were discussed.     

Tropolones of cupressaceae—III.

Twenty-two samples of heartwood from various Cupressus species were analyzed by paper chromatography to determine the tropolones present. Nootkatin and β-thujaplicin seem to occur in all species. Pygmaein, α-thujaplicinol, and α-dolabrinol occur only in the three cypresses from the California coast—C. pygmea, C. goveniana, and C. abramsiana. γ-Thujaplicin is found in large amounts in two closely related species, C. forbesii (southern California) and C. guadalupensis (Guadalupe Island, Baja California), as well as in C. lusifanica, a species known in cultivation only; it appears sporadically in C. arizonica and in the related species C. glabra. Hydronootkatinol and β-thujaplicinol are fairly common, usually in small amounts. α-Thujaplicin and β-dolabrin seem to be rare trace constituents.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy — Part III: The Relationship of Minor to Serious Bleeding

In a study of reports of 805 instances of spontaneous bleeding occurring among 2,189 patients receiving long-term anticoagulant drug therapy, 124 episodes were considered serious and 681 minor. There was no significant correlation of minor bleeding and serious bleeding.Minor bleeding unassociated with excessive reduction of coagulability or an underlying organic lesion could not be considered, according to this evidence, an indication for discontinuance of anticoagulant drug therapy.In apparently minor internal bleeding, however, hidden underlying organic lesions must be excluded. If gross hematuria occurs, renal lesions must be excluded.Rectal bleeding must not be considered minor until gastrointestinal lesions have been excluded.     

Chromone-Fused Cytosine Analogues: Synthesis,Biological Activity,and Structure–Activity Relationship

The preparation of a series of novel chromone-fused cytosine analogues, i.e., chromeno[2,3-d]pyrimidines has been carried out from substituted 2-amino-4-oxo-4H-chromene-3-carbonitriles with urea, thiourea, and guanidine under different reaction conditions. These chromone-fused cytosine analogues were evaluated for their in vitro activity against Mycobacterium tuberculosis H₃₇Rv strain and different microbial pathogenic strains in cell culture for their structure–activity relationships, respectively. Among the synthesized compounds, 2d, 3a, and 4e showed better results against Mycobacterium tuberculosis H₃₇Rv. The compounds 2a, 2b, and 3a showed potential antibacterial activity against E. coli and P. aeruginosa, while the majority of compounds were found to be active against S. aureus as compared to ampicillin. The synthesized cytosine analogues having an imine (–C&dbnd;NH) have been less sensitive to the bacterial and fungal strains but have a more beneficial effect on Mycobacterium tuberculosis H₃₇Rv.     

Structure and physiology of euglena spirogyra. III–VI

Archives of Microbiology -     

Inhibition of Vesicular Glutamate Uptake by Rose Bengal-Related Compounds: Structure–Activity Relationship

Synaptic vesicular accumulation of glutamate is a vital initial step in glutamate transmission. We have previously shown that Rose Bengal, a polyhalogenated fluorescein analog, is a potent inhibitor of glutamate uptake into synaptic vesicles. Here, we report the structural features of Rose Bengal required for this inhibition. Various Rose Bengal-related compounds, with systematic structural variations, were tested. Results indicate that the four iodo groups and the phenyl group attached to the xanthene moiety are critical for potent inhibitory activity. Replacement of these groups with two iodo groups and an alkyl group, respectively, results in substantial reduction in potency. Of further interest in creating high potency is the critical nature of the oxygen atom which links the two benzene rings of xanthene. Thus, the phenyl group and multiple iodo groups, as well as the bridging oxygen of xanthene, are crucial elements of Rose Bengal required for its potent inhibitory action.     

Discovery and Structure Activity Relationship of Small Molecule Inhibitors of Toxic β-Amyloid-42 Fibril Formation

Increasing evidence implicates Aβ peptides self-assembly and fibril formation as crucial events in the pathogenesis of Alzheimer disease. Thus, inhibiting Aβ aggregation, among others, has emerged as a potential therapeutic intervention for this disorder. Herein, we employed 3-aminopyrazole as a key fragment in our design of non-dye compounds capable of interacting with Aβ42 via a donor-acceptor-donor hydrogen bond pattern complementary to that of the β-sheet conformation of Aβ42. The initial design of the compounds was based on connecting two 3-aminopyrazole moieties via a linker to identify suitable scaffold molecules. Additional aryl substitutions on the two 3-aminopyrazole moieties were also explored to enhance π-π stacking/hydrophobic interactions with amino acids of Aβ42. The efficacy of these compounds on inhibiting Aβ fibril formation and toxicity in vitro was assessed using a combination of biophysical techniques and viability assays. Using structure activity relationship data from the in vitro assays, we identified compounds capable of preventing pathological self-assembly of Aβ42 leading to decreased cell toxicity.