Importance of Neem Leaf: An insight into its role in combating diseases

708-718The neem (Azadirachta indica A. Juss) is a tropical evergreen tree (Fam. Meliacae; Subfam. Melioideae) traditionally well known for its medicinal value. Beneficialt effects of different parts of neem are attributed to its biologically active principle ‘Azadirachtin’. Apart from Indian subcontinent, neem is widely used in African countries as therapeutics, preservatives and insecticides. Neem leaves, natural source of flavonoids, polyphenols, isoprenoids, sulphurous and polysaccharides, play important role in scavenging the free radical and subsequently arresting disease pathogenesis. Considerable research has gone into neem for developing cost effective and non-toxic products. The present review has compiled different phytochemicals isolated from neem leaves, methods of extraction and their therapeutic use in preventing several diseases. Here, we highlighted the mechanism of anti-inflammatory and antioxidant activity of neem leaf that underscores the disease through regulation of physiological responses. Also, multiple roles of neem leaf and commercial use of neem formulation as an alternative in paving a frontier in the field of drug discovery are discussed

Efficient Synthesis of Novel Tetrahydropyrrolo[30,40:3,4]Pyrrolo[2,1-a] Isoquinoline Derivatives via a Simple and Convenient MCR in Aqueous Micellar System

A simple and efficient one-pot three component synthesis of tetrahydropyrrolo[30,40:3,4]pyrrolo[2,1- a]isoquinoline-9,11-dione derivatives has been achieved from variously substituted isoquinolines, 2- bromo acetophenone and N-aryl maleimide derivatives in an aqueous micellar medium. The synthesis represents an environmentally benign alternative to classical method

Hydrodynamic optimization of bulk and tank ship hulls

International shipping transports more than 80 percent of global trade. Traditionally bulk carriers have been built to minimize construction cost and maximize cargo-carrying capacity, neglecting hydrodynamic characteristics. By 2025, all new ships will be required to be 30% more energy efficient than those built in 2014. When designing bulk ships, a number of restrictions have already been applied even before the naval architect has stated designing the ship, e.g. port restrictions, canals and legislative limitations. This thesis investigate how speed performance and power requirements may be improved by lifting some of the restriction on main dimensions when designing ship hulls. Lindstad et al. (2013) introduce the idea that increasing the breadth of bulk carriers while keeping the length, draft and displacement constant, and thereby reducing the block coefficient, will be an efficient way of reducing the resistance and fuel consumption of a ship. Lindstad et al. (2013) uses an empirical model based on Holtrop and Mennen (1984) and conclude that the brake power is reduced with reduced block coefficient. However, when evaluating hull dimensions outside the range the empirical data is based on, the result obtained has high uncertainty. Numerical methods using CFD has been applied in combination with CAD program to optimize hull lines. Using CFD to calculate added resistance in waves is however very computational demanding and time consuming and can hardly be applied in an optimization process. By using a simplified numerical method on a wide range of hull designs, this thesis attempts to bridge the gap between the idea of Lindstad et al. (2013) and the numerical approach used in simulation based design. Based on an adaption of a commercial bulk carrier (CBC) and MOERI KVLCC2 there has been designed two series of ships with a deadweight of 80 000 tons. The block coefficient varies from 0,59 to 0,8 for the MOERI KVLCC2 series and 0,64 to 0,87 for the CBC series. When designing the hull and ship lines the focus has been on optimizing the bow, the transition between the bow and parallel midship area (forward shoulder), the parallel midship body and the stern area. Initially, the two numerical calculations programs ShipX and Michlet was tested. ShipX calculates the wave resistance of conventional monohull ships using potential theory. To make ShipX more robust it satisfies the boundary condition of the surface some distance away from the hull surface. The satisfying of the boundary condition makes it less prone to catch details in different hulls. Using Geritsma & Beukelman method combined with strip-theory approximation the added resistance in waves is calculated. Michlet is an open source research code utilizing thin ship theory to calculate wave resistance. The essential assumption is that the hull is thin, that is, the breadth is small compared to all other characteristic lengths of the problem. A benchmarking with the MOERI KVLCC2 show that results from ShipX are correlating best with experimental results. ShipX is therefore used to calculate the calm water resistance and added resistance in waves for the two design series. When comparing the brake power as a function of block coefficient calculated using empirical and numerical methods there is a clear disagreement in the results. For both of the design series the empirical calculations show a decreasing brake power with decreasing block coefficient, giving no clear optimum. For the CBC series the numerical calculations show an optimal block coefficient of 0,73. For the MOERI KVLCC2 series the numerical calculations show an optimal block coefficient of 0,78. In additions, results indicate that for a given block coefficient moving the longitudinal center of buoyancy (LCB) backward reduce the wave resistance. From the results it is concluded that the optimal block coefficient for ships in the New Panamax and Capesize segment (60 00

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2 a]furoquinolines/ phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

A new series of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and pyrrolo[1,2-a]phenanthrolines were efficiently built up from an 8-hydroxyquinoline derivative or phenanthroline via 1,3-dipolar cycloaddition reaction involving non-stabilized azomethine ylides, generated in situ from the parent furo[3,2-h]quinoliniums/phenanthroliums, in presence of a copper(II) chloride–phenanthroline catalytic system. The methodology combines general applicability with high yields

Isolation, structural elucidation and cytotoxicity evaluation of a new pentahydroxy-pimarane diterpenoid along with other chemical constituents from <i>Aerva lanata</i>

<div><p><i>Aerva</i><i>lanata</i> possesses various useful medicinal and pharmaceutical activities. Phytochemical investigation of the plant has now led to the isolation of a new 2α,3α,15,16,19-pentahydroxy pimar-8(14)-ene diterpenoid (<b>1</b>) together with 12 other known compounds identified as β-sitosterol (<b>2</b>), β-sitosterol-3-<i>O</i>-β-D-glucoside (<b>3</b>), canthin-6-one (<b>4</b>), 10-hydroxycanthin-6-one (aervine, <b>5</b>), 10-methoxycanthin-6-one (methylaervine, <b>6</b>), β-carboline-1-propionic acid (<b>7</b>), 1-<i>O</i>-β-D-glucopyranosyl-(2<i>S</i>,3<i>R</i>,8<i>E</i>)-2-[(2′<i>R</i>)-2-hydroxylpalmitoylamino]-8-octadecene-1,3-diol (<b>8</b>), 1-<i>O</i>-(β-D-glucopyranosyl)-(2<i>S</i>,3<i>S</i>,4<i>R</i>,8<i>Z</i>)-2-[(2′<i>R</i>)-2′-hydroxytetracosanoylamino]-8(<i>Z</i>)-octadene-1,3,4-triol (<b>9</b>), (2<i>S</i>,3<i>S</i>,4<i>R</i>,10<i>E</i>)-2-[(2′<i>R</i>)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (<b>10</b>), 6′-<i>O</i>-(4″-hydroxy-trans-cinnamoyl)-kaempferol-3-<i>O</i>-β-D-glucopyranoside (tribuloside, <b>11</b>), 3-cinnamoyltribuloside (<b>12</b>) and sulfonoquinovosyldiacylglyceride (<b>13</b>). Among these, six compounds (<b>8</b>–<b>13</b>) are reported for the first time from this plant. Cytotoxicity evaluation of the compounds against five cancer cell lines (CHO, HepG2, HeLa, A-431 and MCF-7) shows promising IC₅₀ values for compounds <b>4</b>, <b>6</b> and <b>12</b>.</p></div

Two new cycloartane type triterpenes from <i>Dysoxyllum binectariferum</i>

Dysoxyllum binectariferum is an important medicinal plant known for various biological activities like anti-inflammatory, CNS depressants, contraceptive, analgesic, immunomodulatory, antimalarial, antifeedant, leishmanicidal and antiviral. It is a rich source of rohitukine, a basic skeleton of flavopiridol. Phytochemical investigation of chloroform extracts of Dysoxyllum binectariferum leaves, lead to the isolation of beddomeilactone (1) and two new cycloartane type triterpenoids beddomeilactol (2) and binectarilactone-A (3) with modified A ring. Compounds were assessed for their in-vitro α-glucosidase inhibitory activity. Compound 1 was found to be most potent, showing IC50 of 17.99 ± 0.26 µg/ml which is comparable to the positive control acarbose.</p

Semisynthesis of Novel Dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione Natural Product Hybrids of Parthenin Followed by Their Cytotoxicity Evaluation

Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS). Here, we use weed Parthenium hysterophorus as a source of parthenin for synthesis of novel dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione natural product hybrids of parthenin via chemo-, regio-, and stereoselective azomethine ylide cycloaddition. All synthesized compounds were characterized through a detailed analysis of one-dimensional (1D) and two-dimensional (2D) NMR and HRMS data, and the stereochemistries of the compounds were confirmed by X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against four cell lines (HCT-116, A549, Mia-Paca-2, and MCF-7), and compound 6 inhibited the HCT-116 cells with an IC50 of 5.0 ± 0.08 μM

Semisynthesis of Novel Dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione Natural Product Hybrids of Parthenin Followed by Their Cytotoxicity Evaluation

Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS). Here, we use weed Parthenium hysterophorus as a source of parthenin for synthesis of novel dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione natural product hybrids of parthenin via chemo-, regio-, and stereoselective azomethine ylide cycloaddition. All synthesized compounds were characterized through a detailed analysis of one-dimensional (1D) and two-dimensional (2D) NMR and HRMS data, and the stereochemistries of the compounds were confirmed by X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against four cell lines (HCT-116, A549, Mia-Paca-2, and MCF-7), and compound 6 inhibited the HCT-116 cells with an IC50 of 5.0 ± 0.08 μM

Tamarixetin 3‑O‑β‑D‑Glucopyranoside from Azadirachta indica Leaves: Gastroprotective Role through Inhibition of Matrix Metalloproteinase‑9 Activity in Mice

Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant. Although previous studies have reported the antiulcer activity of neem leaf extract, the lead compound is still unidentified. The present study reports tamarixetin 3-O-β-D-glucopyranoside (1) from a methanol extract of neem leaves and its gastroprotective activity in an animal model. Compound 1 showed significant protection against indomethacin-induced gastric ulceration in mice in a dose-dependent manner. Moreover, ex vivo and circular dichroism studies confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity with an IC50 value of ca. 50 μM. Molecular docking and dynamics showed the binding of 1 into the pocket of the active site of MMP-9, forming a coordination complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity

Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection

Curcumin has been transformed to racemic curcuminoids via an azomethine ylide cycloaddition reaction using isatin/ acenaphthoquinone and proline as the reagents. The products were characterized by extensive 1D/2D NMR analysis and single-crystal X-ray crystallographic studies. The enantiomers of one racemic product were separated by HPLC on a Chiralcel OD-H column and were indeed confirmed by the CD spectra of the separated enantiomers