Promoting crucial team building, collaboration, and communication skills in graduate students through interactive retreats.

Biomedical graduate students receive intensive training in their scientific area of interest yet need additional skills for successful scientific careers. Our aim was to promote team building, improve collaborations and enhance communication skills. An off-site yearly retreat was organized for the graduate students in our NIH-funded Research Initiative for Scientific Enhancement (RISE) graduate training program.

Safety assessment of coleopteran active IPD072Aa protein from Psuedomonas chlororaphis.

The ipd072Aa gene from Pseudomonas chlororaphis encodes the IPD072Aa protein which confers protection against certain coleopteran pests when expressed in genetically modified (GM) plants. A weight of evidence approach was used to assess the safety of the IPD072Aa protein. This approach considered the history of safe use of the source organism and bioinformatic comparison of the protein sequence with known allergenic and toxic proteins.

E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes.

As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy-4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v).

Antineoplastic agents. 536. New sources of naturally occurring cancer cell growth inhibitors from marine organisms, terrestrial plants, and microorganisms(1a,).

Bioassay-guided fractionation of extracts of various plants, marine organisms, and microorganisms has led to the discovery of new natural sources of a number of known compounds that have significant biological activity. The isolation of interesting and valuable cancer cell growth inhibitors including majusculamide C ( 1), axinastatin 5 ( 5), bengazoles A ( 6), B ( 7), and E ( 8), manzamine A ( 10), jaspamide ( 11), and neoechinulin A ( 19) has been summarized.

Antineoplastic agents. 445. Synthesis and evaluation of structural modifications of (Z)- and (E)-combretastatin A-41.

A series of cis- and trans-stilbenes related to combretastatin A-4 (1a), with a variety of substituents at the 3'-position of the aryl B-ring, were synthesized and evaluated for inhibitory activity employing six human cancer cell lines (NCI-H460 lung carcinoma, BXPC-3 pancreas, SK-N-SH neuroblastoma, SW1736 thyroid, DU-145 prostate, and FADU pharynx-squamous sarcoma) as well as the P-388 murine lymphocyte leukemia cell line. Several of the cis-stilbene derivatives were significantly inhibitory against all cell lines used, with potencies comparable to that of the parent 1a. All were potent inhibitors of tubulin polymerization.

Antineoplastic agents. 534. isolation and structure of sansevistatins 1 and 2 from the African Sansevieria ehrenbergii.

Using bioactivity-directed isolation procedures, three new spirostanol saponins designated sansevierin A (1), sansevistatin 1 (2), and sansevistatin 2 (3) were isolated (10(-5) % yield) from the CH3OH-CH2Cl2 extract of Sansevieria ehrenbergii, accompanied by three known steroidal saponins (4-6). The structures were determined on the basis of chemical methods and spectroscopic analysis, especially 1D and 2D NMR experiments. Each of the saponins was evaluated against the P388 lymphocytic leukemia cell line and a panel of human cancer cell lines.

Antineoplastic agents 470. Absolute configuration of the marine sponge bromopyrrole agelastatin A.

Two bromopyrrole marine alkaloids were isolated from the Mexican sponge, Agelas sp.: hymenidin (1) and agelastatin A (2). The structures were elucidated by analysis of their spectroscopic data and found to correspond to those in the literature.

Antineoplastic Agents. 510. Isolation and structure of dolastatin 19 from the Gulf of California sea hare Dolabella auricularia.

The Gulf of California shell-less mollusc Dolabella auricularia has been found to contain a new 14-membered macrocyclic lactone linked to a 2,4-di-O-methyl-l-alpha-rhamnopyranoside, designated dolastatin 19 (1). The new cancer cell growth inhibitor (1, 8.33 x 10(-8)% yield) was obtained by bioassay (P388 lymphocytic leukemia and human cancer cell lines) directed isolation, accompanied by debromoaplysiatoxin (9.

Antineoplastic agents. 380. Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp. and conversion to the phosphate prodrug hystatin 1.

By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp. were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4). The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized.

Antineoplastic agents. 499. Synthesis of hystatin 2 and related 1H-benzo[de][1,6]-naphthyridinium salts from aaptamine.

The marine sponge constituent aaptamine (1) has been converted to the cancer cell growth inhibitor and antibiotic designated hystatin 2 (8a). Herein, we also report results of an initial SAR evaluation of new benzyl derivatives of aaptamine (1). Single benzylation was found to occur at nitrogen N-4 and led to the formation of the 4-benzylaaptamine derivatives 7a-c, whereas double benzylation gave the quaternary 1H-benzo[de][1,6]-naphthyridinium salts 8a-c.

Antineoplastic agents. 520. Isolation and structure of irciniastatins A and B from the Indo-Pacific marine sponge Ircinia ramosa.

The Indo-Pacific marine sponge Ircinia ramosa has been found to contain two powerful (GI50 from 0.001 to <0.0001 microg/mL) murine and human cancer cell growth inhibitors.

Isolation and structure of palstatin from the Amazon tree Hymeneae palustris(1).

Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines) guided separation of an extract prepared from the leaves of Hymenaea palustris Ducké led to the isolation of six cancer cell growth inhibitory flavonoids (1-6). The structures were elucidated by HRMS and 1D and 2D NMR spectral analysis. The new flavonolignan 1 designated palstatin proved to be a methoxy structural modification of 5'-methoxyhydnocarpin-D (2).

Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia.

The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.

Isolation of labradorins 1 and 2 from Pseudomonas syringae pv. coronafaciens.

Investigation of Pseudomonas syringae pv. coronafaciens cancer cell growth inhibitory constituents led to the isolation of 2-isobutyl-5-(3-indolyl)oxazole (1) and 2-n-pentyl-5-(3-indolyl)oxazole (2f), designated labradorins 1 (1) and 2 (2f), related to pimprinine (2a). The structures were deduced by spectroscopic techniques and X-ray crystal structure determinations.

Synthesis and biological evaluation of a spongistatin AB-spiroketal analogue.

The synthesis of a simplified analogue of the potent, cytotoxic tubulin-depolymerizing agent spongistatin 1, based on the AB spiroketal framework, is presented. The new structural analogue is an extension of a recently described spongistatin congener reported to disrupt microtubules in breast cancer cells in vitro and to alter the microtubule assembly reaction. Cytotoxicity data on the new structural analogue, as well as the parent congener, are reported.

Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate.

As an extension of structure/activity investigations of resveratrol (1), phenstatin (2c), and the cancer antiangiogenesis drug sodium combretastatin A-4 phosphate (2b), syntheses of certain related stilbenes (14) and benzophenones (16) were undertaken. The trimethyl ether derivative of (Z)-resveratrol (4a) exhibited the strongest activity (GI(50) = 0.01-0.