MODEL DEVELOPMENT AND PROCESS OPTIMIZATION FOR SOLVENT EXTRACTION OF POLYPHENOLS FROM RED GRAPES USING BOX–BEHNKEN DESIGN

The objective of the present study is to find out the optimum extraction conditions for extraction of polyphenols from red grapes using Box–Behnken design. Red grapes polyphenols were extracted using acid–ethanol solvent at various extraction temperature (40–60°C), extraction time (20–100 min) and different solid–liquid ratio (1:5–1:15 g:ml). The effect (main and interactive) of extraction conditions on total anthocyanin, phenolic and flavonoid content were studied using Box–Behnken design (three factors at three levels). The results showed that the contribution of the quadratic model was significant for all the responses. Second-order mathematical regression models were developed and were found to fit well with observed data. Derringer's desirability function methodology was performed to find out the optimal conditions based on both individual and combinations of all responses (extraction temperature: 57°C, time: 61 min, and solid–liquid ratio: 1:8.7 g:ml) were established. At this optimal condition, the anthocyanin yield, total phenolic and flavonoid content were 73.92 mg/100 g, 221.4 mg GAE/100 g, and 79.08 mg CE/100 g, respectively. A desirability value of 0.902 was achieved at this point.     

Molecular encapsulation of berberine by a modified β-cyclodextrin and binding of host: guest complex to G-quadruplex DNA

Abstract

The capacity to control quadruplex formation, especially in cancer cells, is captivating and entails a reasonable comprehension of the ligand-G-quadruplex binding. Herein, we report an iminopyrenyl-β-cyclodextrin conjugate interacting with duplex and G-quadrulex DNAs. In addition, the host: guest association of the established G-quadruplex binder, berberine, with the β-cyclodextrin derivative is studied employing 2-D ROESY. NMR, UV-visible, and fluorescence spectroscopic techniques are utilized to explore the β-cyclodextrin conjugate's interaction with the quadruplexes. The Binding constants are accounted for the association of the ligands to each of the DNAs viz., calf thymus DNA (duplex), kit22, telo24, and myc22 (quadruplexes). The modulation of the iminopyrenyl-β-cyclodextrin binding to the DNAs are observed when berberine is loaded in the host molecule. A vivid distinction between the interactions of the ligands with duplex and quadruplex structures is inferred. Berberine-loaded iminopyrenyl-β-cyclodextrin shows a higher affinity for binding to kit22.     

Synthesis of Brunfelsamidine Ribonucleoside and Certain Related Compounds by the Stereospecific Sodium Salt Glycosylation Procedure

Abstract

A synthesis of 2,4-dideazaribavirin ( 2 ), brunfelsamidine ribonucleoside ( 8c ) and certain related derivatives are described for the first time using the stereospecific sodium salt glycosylation procedure. Glycosylation of the sodium salt of pyrrole-3-carbonitrile ( 4 ) with 1-chloro-2, 3-O-t-isopropylidene-5-O-t-butyldimethylsilyl-α-D-ribofuranose ( 5 ) gave exclusively the corresponding blocked nucleoside ( 6 ) with β-anomeric configuration, which on deprotection provided 1-β-D-ribofuranosylpyrrole-3-carbonitrile ( 7 ). Functional group tranformation of 7 gave 2 , 8c and related 3-substituted pyrrole ribonucleosides. These compounds are devoid of any significant antiviral/antitumor activity invitro.     

Short and Straightforward Synthesis of Triphosphates of Artificial Nucleobase Pairs Displaying Unconventional Pairing Scheme

Concise, facile and efficient synthesis of 5′-O-triphosphates of 6-amino-5-nitro-3-(1′-β-D-2′-deoxyribofuranosyl)-2(1H)-pyridone (dZ) and its Watson-Crick complement 2-amino-8-(1′-β-D-2′-deoxyribofuranosyl)-imidazo[1,2a]-1,3,5-triazin-4(8H)-one (dP) is reported using a one-pot synthetic procedure.     

Synthesis of Zidovudine Derivatives with Anti-HIV-1 and Antibacterial Activities

Twelve novel zidovudine derivatives were prepared by modifying 5 ′-hydroxyl group of sugar moiety (1–8) and 5-methyl group of thymidine nucleus (9–12) and characterized spectrally. The compounds were evaluated for anti-HIV-1, antitubercular and antibacterial activities. Compound (3-azido-tetrahydro-5- (3,4-dihydro-5-methyl-2,4-dioxopyrimidin- 1 (2H)-yl) furan-2-yl)methyl 7- (4- (2-phenylacetoyloxy) -3,5- dimethylpiperazin-1-yl) -5- (2-phenylacetoyloxyamino) -1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (5) was found to be the most potent anti-HIV-1 agent with EC₅₀ of 0.0012 μM against HIV-1_IIIB and CC₅₀ of 34.05 μM against MT-4 with selectivity index of 28,375. Compound 5 inhibited Mycobacterium tuberculosis with MIC of 1.72 μM and inhibited four pathogenic bacteria with MIC of less than 1 μM.     

Design,Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors

Targeting papain family cysteine proteases is one of the novel strategies in the development of chemotherapy for a number of diseases. Novel cysteine protease inhibitors derived from 1-pyridylimidazo[1,5-a]pyridine representing pharmacologically important class of compounds are being reported here for the first time. The derivatives were initially designed and screened in silico by molecular docking studies against papain to explore the possible mode of action. The molecular interaction between the compounds and cysteine protease (papain) was found to be very similar to the interactions observed with the respective epoxide inhibitor (E-64c) of papain. Subsequently, compounds were synthesized to validate their efficacy in wet lab experiments. When characterized kinetically, these compounds show their K_i and IC₅₀ values in the range of 13.75 to 99.30 µM and 13.40 to 96.50 µM, respectively. The thermodynamics studies suggest their binding with papain hydrophobically and entropically driven. These inhibitors also inhibit the growth of clinically important different types of Gram positive and Gram negative bacteria having MIC₅₀ values in the range of 0.6–1.4 µg/ml. Based on Lipinski’s rule of Five, we also propose these compounds as potent antibacterial prodrugs. The most active antibacterial compound was found to be 1-(2-pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine (3a).     

Behavioural Lateralization in Budgerigars Varies with the Task and the Individual

Handedness/footedness and side biases are a well-known phenomenon in many animals, including humans. However, these so-called biases have mostly been studied at the population level - individual biases have received less attention, especially with regard to consistency over different tasks. Here we investigate behavioral lateralization in 12 male Budgerigars, Melopsittacus undulatus, a social parrot inhabiting the Australian bushlands. We performed 5 types of experiments to investigate lateralization, in tasks that involved climbing onto a perch, or landing on perches arranged in various configurations. The birds displayed highly significant, individually varying biases. The bias displayed by any particular individual varied with the task, in strength as well as polarity. Analysis of the data revealed that the preferred foot used for climbing did not coincide with the foot that was used while landing. Thus, landing choices are probably not determined by foot bias. Furthermore, these individual preferences were overridden completely when a bird had to perform a task simultaneously with another bird.     

Non-contiguous finished genome sequence and description of Kallipyga massiliensis gen. nov., sp. nov., a new member of the family Clostridiales Incertae Sedis XI

Kallipyga massiliensis strain ph2^T is the type strain of Kallipyga massiliensis gen. nov., sp. nov., the type species of the new genus Kallipyga within the family Clostridiales Incertae Sedis XI. This strain, whose genome is described here, was isolated from the fecal flora of a 26-year-old woman suffering from morbid obesity. K. massiliensis is an obligate anaerobic coccus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 1,770,679 bp long genome (1 chromosome but no plasmid) contains 1,575 protein-coding and 50 RNA genes, including 4 rRNA genes.     

The Histone Variant His2Av is Required for Adult Stem Cell Maintenance in the Drosophila Testis

Many tissues are sustained by adult stem cells, which replace lost cells by differentiation and maintain their own population through self-renewal. The mechanisms through which adult stem cells maintain their identity are thus important for tissue homeostasis and repair throughout life. Here, we show that a histone variant, His2Av, is required cell autonomously for maintenance of germline and cyst stem cells in the Drosophila testis. The ATP-dependent chromatin-remodeling factor Domino is also required in this tissue for adult stem cell maintenance possibly by regulating the incorporation of His2Av into chromatin. Interestingly, although expression of His2Av was ubiquitous, its function was dispensable for germline and cyst cell differentiation, suggesting a specific role for this non-canonical histone in maintaining the stem cell state in these lineages.