A review of the genus Aleurolobus Quaintance and Baker (Hemiptera: Aleyrodidae) from Taiwan, based mainly on pupal morphology with a description of a new species

The whitefly species of the genus Aleurolobus Quaintance and Baker are reviewed from Taiwan. A total of nine species are included. Aleurolobus shiiae Takahashi is new to Taiwan. Aleurolobus osmanthi Young is considered as a junior synonym of Aleurolobus taonabae (Kuwana). A new species, Aleurolobus rubus Dubey and Ko, is described, and the puparia of the new species are diagnosed in a combination of characters: the dorsal pores scattered over dorsum; each located on a large subcircular, chitinised cuticular dorsal marking; faint eye spots; broader submargin; and the vasiform orifice set anterior to the caudal end of puparium by nearly twice of its own length. The record of Aleurolobus philippinensis Quaintance and Baker, and Aleurolobus setigerus Quaintance and Baker from Taiwan is discussed. The puparial diagnosis of each species, identification key to species so far known from Taiwan and illustrations for each species are provided.     

Compositae of the Guayana Highland—VII. Noteworthy species of Chromolaena and Mikania (Eupatorieae) from Venezuela

Chromolaena ternicapitulata is described from Sierra de Maigualida in T. F. Amazonas and a key to the species of Chromolaena from Guayana is given. Newly documented for the flora of Venezuela are M. aschersonii Hieron. and M. amazonica Baker, the second herein resurrected from the synonymy of common and widespread M. sprucei Baker. Mikania karsteniana Klot. ex Hieron. is not considered synonymous with M. pannosa Baker, thus the latter is again considered to be endemic to Guayana.     

A new species and a new combination in the genus Eucrosia (Amaryllidaceae)

Eucrosia dodsonii is described from Ecuador andLeperiza eucrosioides Baker is combined withEucrosia asE. brachyandra.     

Taxonomic considerations of piptocarpha (Compositae: Vernonieae) and new taxa in Brazil

The distribution, affinities and delimiting characters and prospects for a new classification ofPiptocarpha are discussed. Two new species and one subspecies from Brazil are described and figured:Piptocarpha densifolia, P. ramboi andP. rotundifolia (Less.) Baker subsp.hatschbachii.     

Furofuran lignans as a new series of antidiabetic agents exerting α-glucosidase inhibition and radical scarvenging: Semisynthesis,kinetic study and molecular modeling

A new series of furofuran lignans containing catechol moiety were prepared from the reactions between lignans and a variety of phenolics. All 22 products obtained were evaluated against three different α-glucosidases (maltase, sucrase and Baker’s yeast glucosidase) and DPPH radical. Of furofuran lignans evaluated, β-14, having two catechol moieties and one acetoxy group, was the most potent inhibitor against Baker’s yeast, maltase, and sucrase with IC₅₀ values of 5.3, 25.7, and 12.9 µM, respectively. Of interest, its inhibitory potency toward Baker’s yeast was 28 times greater than standard drug, acarbose and its DPPH radical scavenging (SC₅₀ 11.2 µM) was 130 times higher than commercial antioxidant BHT. Subsequent investigation on mechanism underlying the inhibitory effect of β-14 revealed that it blocked Baker’s yeast and sucrase functions by mixed-type inhibition while it exerted non-competitive inhibition toward maltase. Molecular dynamics simulation of the most potent furofuran lignans (4, α-8b, α-14, and β-14) with the homology rat intestinal maltase at the binding site revealed that the hydrogen bond interactions from catechol, acetoxy, and quinone moieties of furofuran lignans were the key interaction to bind tightly to α-glucosidase. The results indicated that β-14 possessed promising antidiabetic activity through simultaneously inhibiting α-glucosidases and free radicals.     

New polyhydroxytriterpenoid derivatives from fruits of Terminalia chebula Retz. and their α-glucosidase and α-amylase inhibitory activity

Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O-β-d-glycopyranosyl ester (1), 23-O-4′-epi-neochebuloylarjungenin (2), and 23-O-galloylpinfaenoic acid 28-O-β-d-glucopyranosyl ester (17) were isolated from the fruits of Terminalia chebula Retz. along with fourteen known ones. Their structures were elucidated by 1D and 2D NMR spectroscopic data and acid hydrolysis. After evaluating for Baker’s yeast α-glucosidase, rat intestinal α-glucosidase, and porcine pancreatic α-amylase inhibitory activities of all the isolated compounds, 23-O-galloylarjunolic acid (11, IC₅₀ 21.7 μM) and 23-O-galloylarjunolic acid 28-O-β-d-glucopyranosyl ester (12, IC₅₀ 64.2 μM) showed potent inhibitory activities against Baker’s yeast α-glucosidase compared to the positive control, acarbose (IC₅₀ 174.0 μM). However, all the tested compounds except for the positive control, acarbose, had no or only weak inhibitory activity against rat intestinal α-glucosidase and porcine pancreatic α-amylase.     

Neotropical Segregates from Sida L. (Malvaceae)

Three genera are segregated out ofSida as natural units,viz. Sidastrum E. G. Baker, enlarged from one species to seven,Krapovickasia nom. nov. including four species, andRhynchosida gen. nov. including two species, one described as new from Bolivia,R. kearneyi. Mericarp and calyx morphology are emphasized in delimiting these genera and in defining the residual genusSida, which now assumes a more natural character.     

Association Of Peripheral 5-Hydroxyindole-3-Acetic Acid,A Serotonin Derivative,with Metabolic Syndrome and Low-Grade Inflammation

Objective: The constellation of metabolic abnormalities seen in metabolic syndrome (MetS) has been linked to atherosclerosis and adverse cardiovascular outcomes due to heightened inflammation. Accumulating evidence suggests that peripheral 5-hydroxyindole-3-acetic acid (5-HIAA), the derivative end-product of serotonin (5-HT), might be involved in the pathogenesis of obesity, and abnormal lipid and glucose metabolism. We examined the association between serum 5-HIAA concentrations and MetS and also highly sensitive C-reactive protein (hsCRP).Methods: We assessed 180 healthy adults (110 males and 70 females) in a cross-sectional setting. Anthropometric indices and blood pressure were measured, as were laboratory parameters including fasting 5-HIAA concentrations. The associations between 5-HIAA and individual components of MetS, as well as MetS as a single entity, were investigated with bivariate correlation and logistic regression analyses.Results: Eighty-nine individuals (49.4%) were diagnosed with MetS. Significant correlations were found between 5-HIAA concentrations and age (r = 0.184), waist circumference (r = 0.415), high-density lipoprotein (HDL) cholesterol (r = -0.148), systolic blood pressure (r = 0.374), diastolic blood pressure (r = 0.355), homeostasis model assessment of insulin resistance (r = 0.201), and hsCRP (r = 0.453) were found (P<.05 in all tests). In logistic regression, 5-HIAA was significantly associated with 4 MetS components including central obesity, raised triglycerides, raised blood pressure, and raised fasting plasma glucose (FPG) (P<.05). Moreover, 5-HIAA was a predictor of MetS as a single entity, and the relationship persisted after adjusting for hsCRP (odds ratio [OR] = 4.41, 95% confidence interval [CI]: 2.58-7.67, P<.001).Conclusion: Elevated concentrations of 5-HIAA are seen in individuals with MetS. Increased 5-HIAA is also associated with hsCRP, a marker of chronic lowgrade inflammation underlying MetS.Abbreviations: BMI = body mass index CI = confidence interval FI = fasting insulin FPG = fasting plasma glucose HbA1c = glycated hemoglobin HDL = high-density lipoprotein 5-HIAA = 5-hydroxyindole-3-acetic acid 5-HT = 5-hydroxytryptamine HOMA-IR = homeostatic model assessment of insulin resistance hsCRP = highly sensitive C-reactive protein LDL = low-density lipoprotein MetS = metabolic syndrome OR = odds ratio     

Synthesis,antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety

Tuberculosis is the infectious disease caused by mycobacterium tuberculosis (Mtb), responsible for the utmost number of deaths annually across the world. Herein, twenty-one new substituted 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl-quinoline derivatives were designed and synthesized through multistep synthesis followed by in vitro evaluation of their antitubercular potential against Mtb WT H37Rv. The compound QD-18 was found to be promising with MIC value of 0.5?µg/ml and QD-19 to QD-21 were also remarkable with MIC value of 0.25?µg/ml. Additionally, we have carried out experiments to confirm the metabolic stability, cytotoxicity and pharmacokinetics of these compounds along with kill kinetics of QD-18. These compounds were found to be orally bioavailable and highly effective. Altogether, these results indicate that QD-18, QD-19, QD-20 and QD-21 are promising lead compounds for the development of a novel chemical class of antitubercular drugs.     

A new name in vernonia (Compositae)

Vernonia rigiophylla Schultz-Bip. ex Baker is a later homonym ofV. rigiophylla DC. and therefore a new name,Vernonia elsieae, is proposed for this species.     

Diabetes,obesity, and erectile dysfunction

Background: Diabetes mellitus (DM) and obesity affect large parts of the population in the United States and around the world. These disorders are among the most common risk factors for erectile dysfunction (ED), because of their effects on the vasculature and the hormonal milieu.Objective: This article reviews the current literature on the connection between DM, obesity, and ED.Methods: Using the search terms erectile dysfunction, endothelial dysfunction, hypogonadism, diabetes, and obesity, a systematic review of the available literature in the PubMed database was conducted. Relevant English-language publications (to August 2008) were identified.Results: ED is highly prevalent in men with both DM and obesity, and may act as a harbinger for cardiovascular disease (CVD) in this high-risk population. In addition to male hypogonadism and macrovascular disease, endothelial dysfunction is central to the connection between the metabolic syndrome and ED. Conversely, improved glycemic control and weight loss have been found to improve erectile function.Conclusion: ED is very prevalent in men with DM and obesity. It is increasingly being recognized as an early clinical indicator and motivator for patients with CVD. The role of pharmacologic ED treatments in improving endothelial function is currently being investigated.     

The first target specific,highly diastereoselective synthesis,design and characterization of pyranoquinolinyl acrylic acid diastereomers as potential α-glucosidase inhibitors

In the present investigation we report the first target specific, highly diastereoselective synthesis of new class of pyranoquinolinyl/furoquinolinyl-acrylic acid diastereomers and evaluation of their invitro α-glucosidase inhibitory activity. All the products were thoroughly characterized by ¹H NMR, ¹³C NMR, FT-IR, Mass spectral and CHN analysis. A highly diastereoselective target specific route of synthesis for the biologically active diastereomers were developed by usingchiral catalyst Europium tris[3-heptafluoropropylhydroxyl methylene]-(−)-camphorate (A) or Europiumtris[3-(trifluoromethyl)hydroxylmethylene]-(+)-camphorate (B). It was found that among a set of 4 diastereomeric products obtained, exodiasteromers of pyranoquinolinyl acrylic acid adducts exhibited relatively high α-glucosidase inhibitory activity. The newly synthesized compounds exhibited IC₅₀ values in the range of (0.40 ± 0.02–30.3 ± 0.84 μM) as compared to standard acarbose (IC₅₀ = 0.65 ± 0.02 μM). It was found that compounds 11a, 11c, 11d and 12d were found to be more active than standard acarbose. It was also found that unsubstituted compound (11a) or compounds with chlorine or methoxy substituent (11c, 11d, 12d) showed potential α-glucosidase inhibitory activity. However a reversal in activity was observed with Nitro substituent (11b, 13b) wherein the endodiastereomers were found to be more active than exodiastereomers. Molecular docking studies were used for design of the compound and understand the mode of binding between the compound and target enzyme. A plausible mechanism for the diastereoselective synthesis was also proposed.     

Antimicrobial,anticoagulant, and cytotoxic evaluation of multidrug resistance of new 1,4-dihydropyridine derivatives

A new series of 1,4-dihydropyridine derivatives (2a–h, 3a–e, and 4a–e) were systematically designed and synthesized via ultrasound irradiation methods with easy work-up and good yields. Compounds structures were confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectra. The synthesized compounds were screened for both antimicrobial and anticoagulant activities. Compound 2e (MIC: 0.25?μg/mL) was highly active against Escherichia coli and compound 2c (MIC: 0.5?μg/mL) was also highly active against Pseudomonas aeruginosa compared with ciprofloxacin. (MIC: 1?μg/mL) The antifungal activity of 2c (MIC: 0.5?μg/mL) against Candida albicans was high relative to that of clotrimazole (MIC: 1?μg/mL). Anticoagulant activity was determined by activated partial thromboplastin time (APTT) and prothrombin time (PT) coagulation assays. Compound 4-(4-hydroxyphenyl)-2,6-dimethyl-N³,N⁵-bis(5-phenyl-1,3,4-thiadiazol-2-yl)-1,4-dihydropyridine-3,5-dicarboxamide 3d (>1000?s in APTT assays) was highly active in anticoagulant screening compared with the reference of heparin.Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2c (GI₅₀?=?0.02?μm) against HeLa cell line and 2e (GI₅₀?=?0.03?μm) equipotant against MCF-7 cell line. Therefore, the compounds 2e, 2c and 3d can serve as lead molecules for the development of new classes of antimicrobial and anticoagulant agent.     

Design,synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC₅₀ = 38.3 nM and 8.79 nM).     

Discovery of selective,orally bioavailable inhibitor of mouse chitotriosidase

This article describes our work towards the identification of a potent and selective inhibitor of mouse chitotriosidase (mCHIT1). A series of small molecule inhibitors of mCHIT1 and mAMCase have been developed from early lead compound 1. Examination of synthetized analogues led to discovery of several novel highly potent compounds. Among them compound 9 (OAT-2068) displays a remarkable 143-fold mCHIT1 vs. mAMCase selectivity. To explain the observed SAR molecular docking experiments were performed, which were in line with the experimental data from the enzymatic assays. Inhibitor 9 (OAT-2068) was found to have an excellent pharmacokinetic profile. This, together with high activity and selectivity, makes the compound an ideal and unique tool for studying the role of CHIT1 in biological models.     

Structure-based design,synthesis, and binding mode analysis of novel and potent chymase inhibitors

Based on insight from the X-ray crystal structure of human chymase in complex with compound 1, a lactam carbonyl of the diazepane core was exchanged with O-substituted oxyimino group, leading to amidoxime derivatives. This modification resulted in highly potent chymase inhibitors, such as O-phenylamidoxime 5f. X-ray crystal structure analysis indicated that compound 5f induced movement of the Leu99 and Tyr94 side chains at the S2 site, and the increase in inhibitory activity of O-phenyl amidoxime derivatives suggested that the O-phenyl moiety interacted with the Tyr94 residue. Surface plasmon resonance experiments showed that compound 5f had slower association and dissociation kinetics and the calculated residence time of compound 5f to human chymase was extended compared to that of amide compound 1.     

Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray,ECD, NMR J-based configurational analysis and HSQC overlay experiments

BackgroundThe plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential. In this work, the absolute configurations of three highly oxygenated schiartane-type nortriterpenoids were unequivocally assigned using X-ray, ECD, and J-based configuration analysis and HSQC overlay data.MethodsThe ethanol extract of Kadsura longipedunculata Finet et Gagnep was purified by column chromatography using silica, Sephadex LH-20, and ODS as substrates. To help assign the absolute configuration of schiartane-type nortriterpenoids, X-ray diffraction analysis, ECD experiment compared to ab initio computed data, DP4+ analysis, HSQC overlay, NOESY, and J-based configuration analysis were carried out. Hetero- and homo-nuclear coupling constants were extracted from HETLOC experiments.ResultsThree new highly oxygenated triterpenoids, micrandilactone I (1), micrandilactone J (2), and 22,23-di-epi-micrandilactone J (3) were isolated. Their 2D structures were solved using NMR and HRESIMS data and their absolute configurations were elucidated using X-ray diffraction analysis, ECD experimental results compared to ab initio computed spectra, HSQC overlay, DP4+, NOESY, and J-based configuration analysis. Micrandilactone I (1) and 22,23-di-epi-micrandilactone J (3) showed moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells with cell survival rates of 53.0 and 50.2%, respectively, at 10 μM (bicyclol, 49.0%), while micrandilactone J (2) was inactive.General significanceThis is the first comprehensive stereochemical assignment of a non-crystalline schiartane-type nortriterpenoid like 3. This general protocol may contribute towards solving the problems hampering the assignment of the absolute configurations of other members of this class of nortriterpenoids.     

Discovery of 2,6–difluorobenzyl ether series of phenyl ((R)–3–phenylpyrrolidin–3–yl)sulfones as surprisingly potent,selective and orally bioavailable RORγt inverse agonists

In an effort to discover oral inverse agonists of RORγt to treat inflammatory diseases, a new 2,6–difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)–3–phenylpyrrolidin–3–yl)sulfone template, the 2,6–difluorobenzyl ethers yielded a set of very potent RORγt inverse agonists (e.g., compound 26, RORγt Gal4 EC₅₀ 11 nM) that are highly selective against PXR, LXRα and LXRβ. After optimizing for stability in human and mouse liver microsomes, compounds 29 and 38 were evaluated in vivo and found to have good oral bioavailability (56% and 101%, respectively) in mice. X–ray co–crystal structure of compound 27 in RORγt revealed that the bulky benzyl ether group causes helix 11 of the protein to partially uncoil to create a new, enlarged binding site, which nicely accommodates the benzyl ether moiety, leading to net potency gain.     

Synthesis,antioxidant, antifungal,molecular docking and ADMET studies of some thiazolyl hydrazones

Some thiazolyl hydrazones were synthesized by one pot reaction of thiophene-2-carbaldehyde or 2, 4-dichlorobenzaldehyde, thiosemicarbazide and various phenacyl bromides which were preliminarily screened for in vitro antioxidant and antifungal activities. Excellent DPPH and H₂O₂ radical scavenged antioxidant activities were observed with almost all the tested compounds. Compounds 4a, 4b, 4c, 4e, 4f and 4i showed comparable DPPH scavenged antioxidant potential (90.26–96.56%) whereas H₂O₂ scavenged antioxidant activity (90.98–92.08%) was noticeable in case of 4a and 4f; showing significant antioxidant potential comparable with the standard ascorbic acid (95.3%). In vitro antifungal activity of synthesized compounds against fungal species Candida albicance, Aspergillus niger and Aspergillus flavus was found to be moderate to good as compared with the standard fluconazole and MIC values were found in the range of 3.12–25 μg/mL. Molecular docking studies revealed that the compounds 4a, 4b and 4c have a potential to become lead molecules in drug discovery process. In silico ADMET study was also performed for predicting pharmacokinetic and toxicity profile of the synthesized antioxidants which expressed good oral drug like behaviour and non-toxic nature.