Intergrain scattering in polycrystals.

Transport through grain boundaries in polycrystals is described from first principles using quantum scattering theory, explicitly including Feshbach resonances to account for intermittently trapped electronic surface states. An effective-matrix is derived then used to calculate the electrical conductivity which exhibits breakdown, a sharp increase at a critical intergrain bias. Under typical conditions where the electron thermal energy,kBT, is much less than the intergrain barrier height,φb, the electrical conductivity has the formσ∼T-1/2e-φb/kBT.

Plant Endophytes and Epiphytes: Burgeoning Sources of Known and "Unknown" Cytotoxic and Antibiotic Agents?

In the last 20 or so years, the influence of endophytes and, quite recently, epiphytes of plants upon the compounds found in those plants, which were usually assumed to be phytochemicals produced by the plant for a variety of reasons, often as a defense against predators, is becoming more evident, in particular in the case of antitumor agents originally isolated from plant sources, though antibiotic agents might also be found, particularly from epiphytes. In this review, we started with the first report in 1993 of a taxol-producing endophyte and then expanded the compounds discussed to include camptothecin, the vinca alkaloids, podophyllotoxin, and homoharringtonine from endophytic microbes and then the realization that maytansine is not a plant secondary metabolite at all, and that even such a well-studied plant such as has a vast repertoire of potential bioactive agents in its leaf epiphytic bacteria. We have taken data from a variety of sources, including a reasonable history of these discoveries that were not given in recent papers by us, nor in other papers covering this topic.

Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates.

In this review, we have attempted to describe all of the antibody-drug conjugates using a marine-derived compound as the "warhead", that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, we used the beta-test version currently available, as it permitted more specific search parameters, since the regular version did not always find trials that had been completed in the past with some agents.

Drugs and Drug Candidates from Marine Sources: An Assessment of the Current "State of Play".

The potential of the marine environment to produce candidate compounds (structures) as leads to, or even direct drugs from, has been actively discussed for the last 50 or so years. Over this time frame, several compounds have led to drugs, usually in the area of cancer (due to funding sources). This review is designed to show where there have been successes, but also to show that in a number of disease areas, there are structures originally isolated from marine invertebrates and free-living microbes that have potential, but will need to be "adopted" by pharmaceutical houses in order to maximize their potential.

Natural Products as Sources of New Drugs from 1981 to 2014.

This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the U.

Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents.

Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy.

Endophytic and epiphytic microbes as "sources" of bioactive agents.

Beginning with the report by Stierle and Strobel in 1993 on taxol((R)) production by an endophytic fungus (Stierle et al., 1993), it is possible that a number of the agents now used as leads to treatments of diseases in man, are not produced by the plant or invertebrate host from which they were first isolated and identified. They are probably the product of a microbe in, on or around the macroorganism.

New horizons for old drugs and drug leads.

There is mounting urgency to find new drugs for the treatment of serious infectious diseases and cancer that are rapidly developing resistance to previously effective drugs. One approach to addressing this need is through drug repurposing, which refers to the discovery of new useful activities for "old" clinically used drugs through screening them against relevant disease targets. A large number of potential drug that, for various reasons, have failed to advance to clinical and commercial use can be added to the candidates available for such purposes.

A correlation between cytotoxicity and reductase-mediated metabolism in cell lines treated with doxorubicin and daunorubicin.

The role of metabolism in daunorubicin (DAUN)- and doxorubicin (DOX)-associated toxicity in cancer patients is dependent on whether the parent drugs or major metabolites, doxorubicinol (DOXol) and daunorubicinol (DAUNol), are the more toxic species. Therefore, we examined whether an association exists between cytotoxicity and the metabolism of these drugs in cell lines from nine different tissues. Cytotoxicity studies using MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide] cell viability assays revealed that four cell lines [HepG2 (liver), HCT-15 (colon), NCI-H460 (lung), and A-498 (kidney)] were more tolerant to DAUN and DOX than the five remaining cell lines [H9c2 (heart), PC-3 (prostate), OVCAR-4 (ovary), PANC-1 (pancreas), and MCF-7 (breast)], based on significantly higher LC50 values at incubation times of 6, 24, and 48 hours.

Natural products: a continuing source of novel drug leads.

Background: Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench.

Natural products as sources of new drugs over the 30 years from 1981 to 2010.

This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.

Antitumor Agents. 282. 2'-(R)-O-acetylglaucarubinone, a quassinoid from Odyendyea gabonensis as a potential anti-breast and anti-ovarian cancer agent.

A new quassinoid, designated 2'-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre]. The structure of 1 was determined by spectroscopic analysis and by semisynthesis from glaucarubolone.

Suppression of auger processes in confined structures.

We explore how the size and shape of the microscopic confinement potential affects the nonradiative Auger decay rate of confined carriers. Calculations conducted in the two-band, effective mass Kane model unambiguously show that smoothing out the confinement potential could reduce the rate by more than 3 orders of magnitude relative to the rate in structures with abruptly terminating boundaries. As the confinement potential width is increased, the calculated rate decreases overall, exhibiting very deep minima at regular widths.

Therapeutic agents from the sea: biodiversity, chemo-evolutionary insight and advances to the end of Darwin's 200th year.

Drugs from the sea? Darwin may not have considered this concept when he was thinking about mechanisms that drove diversification of life on earth. In recognition of his 200th year, and celebration of the publication in 1859 of his "On the origin of species", we review the global status of marine biodiscovery in medicinal fields, with a focus on the South Pacific. Furthermore, in the Darwinian spirit, we touch on putative evolutionary drivers and the chemical ecology of the successful leads.