Justicialosides A and B, two new flavone glycosides from the leaves of Ruspolia hypocrateriformis (Vahl) Milne-Redh. (Acanthaceae)

Two new flavone glycosides, luteolin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (1) and chrysoeriol 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (2), along with five known compounds, luteolin 7-O-β-D-apiofuranosyl-(1→2)-β-D-xylopyranoside (3), grandulosides A and B (4 and 5), luteolin 7-O-[β-D-glucopyranosyl-(1→2)-α-L-rhamnosyl-(1→6)]-β-D-glucopyranoside (6) and 10H-quindoline (7) were isolated from the leaves of Ruspolia hypocrateriformis (Acanthaceae). Their structures were elucidated by spectroscopic means, including 1D and 2D NMR, HRESIMS and by comparison with published data

Four new neo-clerodane diterpenes from the stem bark of Croton oligandrus.

Four new neo-clerodanes, crotonolins C-F (3-6), were isolated from the stem bark of Croton oligandrus together with the known clerodane crotonzambefuran A, the abietanes 7-β-hydroxydehydroabietic acid and 7-oxodehydroabietic acid, and ferulic acid. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR and HRESIMS and by comparison with previously reported data. The cytotoxicity of the isolated compounds against A549, MCF7, PC3 and PNT2 cells was evaluated using the MTT assay. Only 7-β-hydroxydehydroabietic acid showed a moderate level of activity against PC3 cells with an IC50 value of 68.9 ± 6.6 μM

Growth inhibitory activity of biflavonoids and diterpenoids from the leaves of the Libyan Juniperus phoenicea against human cancer cells

Three biflavonoids [cupressuflavone (1), amentoflavone (2)and sumaflavone (3)], four diterpenoids [13-epi-cupressic acid (4), imbricatholic acid (5), 3-hydroxy-sandaracopimaric acid (6)and dehydroabietic acid (7)]and onelignan [β-peltatin methyl ether (8)],were isolated from the cytotoxicfractions of the extracts of the leaves of the Libyan Juniperus phoeniceaL. The structures of these compounds were elucidated by spectroscopic means.Cytotoxicity of the compounds 1-6were assessedagainst the human lung cancer cell lineA549 using the MTT assay. Compounds 1and 3showed cytotoxicityagainst the A549cells(IC50= 65 µMand 77 µM, respectively), whereas, compound 2did not show any activity. Diterpenes4-6exhibited weak cytotoxicity against the A549 cells with the IC50values of 159 µM, 263 µMand 223 µM, respectively. The cytotoxicity of each compound was compared with the anticancer drug,etoposide (IC50=61 µM).Cupressuflavone (1)wasevaluatedalso for cytotoxicity against both the human PC3 cancer cell lineand the normal prostatecell line (PNT2), and this compoundrevealed a high degreeof cytotoxic selectivity towards the prostate cancer cells (PC3), with IC50value of 19.9 µM, without any evidence of cytotoxicity towards the normal prostatecell line(PNT2)

One-pot synthesis and negative ion mass spectrometric investigation of a densely functionalized cinnoline, 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile

Known densely substituted 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile was synthesized using a new synthetic protocol involving chloranil and malonitrile via quinone methide formation. This one-pot synthesis occurs under base mediated conditions in a polar medium. The method involves condensation of excess malononitrile with chloranil in ethanol at reflux to 2-(2,4,5-trichloro-3-hydroxy-6-oxocyclohexa-2,4-dien-1-ylidene) malononitrile. This is an atom efficient, simple and effective procedure for the preparation of a highly substituted cinnoline that can serve as a relay to antimalarial prototypes

Liquid chromatography mass spectrometry analysis and cytotoxicity of Asparagus adscendens roots against human cancer cell lines

Background: Asparagus adscendens Roxb. (Asparagaceae), is native to the Himalayas. This plant has been used in the prevention and effective treatment of various forms of cancers. Objective: This paper reports, for the first time, on the cytotoxicity of the methanol (MeOH) extract of the roots of A. adscendens and its solid‑phase extraction (SPE) fractions against four human carcinoma cell lines and LC‑ESI‑QTOF‑MS analysis of the SPE fractions. Materials and Methods: Finely powdered roots of A. adscendens were macerated in methanol and extracted through SPE using gradient solvent system (water: methanol) proceeded for analysis on LC‑ESI‑QTOF‑MS and cytotoxicity against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549), and urinary bladder (EJ138), using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazoliumbromide assay. Results: The MeOH extract and four SPE fractions exhibited cytotoxicity against all cell lines with the IC50 values ranging from 6 to 79 μg/mL. As observedin other Asparagus species, the presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography‑mass spectrometry data. Conclusion: It is reasonable to assume that the cytotoxicity of the MeOH extract of the roots of A. adscendens and its SPE fractions, at least partly, due to the presence of saponins and their aglycones. This suggests that A. adscendens could be exploited as a potential source of cytotoxic compounds with putative anticancer potential

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor in vivo Using Fluorinated Bisquinolines

Antimalarials can interact with heme covalently, by - interactions or hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen due to electronic rather than steric factors. In gas phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluromethyl groups buttressing quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/6- 31+G*) and crystal structure of (±)-trans-N1,N2-bis-(2,8-ditrifluoromethylquinolin-4- yl)cyclohexane-1,2-diamine were used to reveal preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III)state which has important implications for the future rational design of 4- aminoquinoline antimalarials

Cytotoxicity of the Roots of Trillium govanianum Against Breast (MCF7), Liver (HepG2), Lung (A549) and Urinary Bladder (EJ138) Carcinoma Cells.

Trillium govanianum Wall. (Melanthiaceae alt. Trilliaceae), commonly known as 'nag chhatri' or 'teen patra', is a native species of the Himalayas. It is used in various traditional medicines containing both steroids and sex hormones. In folk medicine, the rhizomes of T. govanianum are used to treat boils, dysentery, inflammation, menstrual and sexual disorders, as an antiseptic and in wound healing. With the only exception of the recent report on the isolation of a new steroidal saponin, govanoside A, together with three known steroidal compounds with antifungal property from this plant, there has been no systematic pharmacological and phytochemical work performed on T. govanianum. This paper reports, for the first time, on the cytotoxicity of the methanol extract of the roots of T. govanianum and its solid-phase extraction (SPE) fractions against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549) and urinary bladder (EJ138), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide cytotoxicity assay and liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry analysis of the SPE fractions. The methanol extract and all SPE fractions exhibited considerable levels of cytotoxicity against all cell lines, with the IC50 values ranging between 5 and 16 µg/mL. Like other Trillium species, presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography mass spectrometry data. Copyright © 2016 John Wiley & Sons, Ltd

Purpurogallin-A heme binding component of oak galls

Recently, it has been shown that Purpurogallin (PPG), an orange benztropolone constituent of oak galls and its derivative, CU-CPT22, can compete with the binding of the specific lipoprotein ligand to toll-like receptors (TLRs), which are type I transmembrane proteins. These recognize pathogen-derived macromolecules that play a key role in the innate immune system. This system provides an attractive target for the treatment of various immune disorders. Notably, PPG also interacts with various metals and its mode of action against HIV in vitro may involve inhibition of metal containing integrases. In the current study, an optimised synthesis of PPG is presented together with its gas phase behaviour (probed by mass spectrometry) as well as its redox behaviour with porphyrins such as heme. This interaction may also explain its effects at metal containing integrases within HIV in vitro as well as its action during processing of iron complexes within Plasmodia. This compound could serve as a novel prototype for the synthesis of novel redox active antimalarials

Accounts of severe acute obstetric complications in Rural Bangladesh

<p>Abstract</p> <p>Background</p> <p>As maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh.</p> <p>Methods</p> <p>Using the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model.</p> <p>Results</p> <p>Women attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors.</p> <p>Conclusions</p> <p>Strategies to increase timely and appropriate care seeking for severe obstetric complications may consider targeting of non-certified providers for strengthening of referral linkages between patients and certified facility-based providers. Future research may characterize the treatments and appropriateness of emergency care provided by ubiquitous village doctors and other non-certified treatment providers in rural South Asian settings. In addition, future studies may explore the use of mobile phones in decreasing delays to certified medical care during obstetric emergencies.</p