Natural Product

Despite their perceived inaccessibility, the marine intertidal and benthic environments of Antarctica, southern Africa and South America have continued to provide marine natural products for chemists with unique opportunities to study the secondary metabolite constituents and chemical ecology of a diverse array of marine gastropod molluscs. This review covers the literature up to 31 January 2005 and describes the structures and, where applicable, biological activities of 100 secondary metabolites isolated from 21 species of marine gastropod molluscs. Not unexpectedly, the chemistry of chemically defended shell-less opisthobranchs dominates the natural product studies of molluscs collected from these regions of the southern hemisphere.

Blends of Cheddar cheese comprising of 66% of 2-3 months old and 34% of 4-5 months old cheddar cheese were used to prepare processed cheese spread. Cheese solids were partially replaced by whey protein concentrate (WPC) (38.00 per cent protein) solids at different levels, viz. 1.5, 3.0 and 4.5 per cent. Incorporation of WPC resulted in a significant improvement in body and texture score of spread particularly at 3.0 and 4.5% level. However, addition of WPC at higher levels imparted a milder flavour to the product. Processed cheese spread with good melt ability, desired characteristics with improved spread ability can be prepared by using dried WPC at levels up to 4.5% of cheese solids.

An oil extracted from the leaves of a tropical shrub Ocimum suave was found to repel as well as kill all stages of the tick Rhipicephalus appendiculatus. In an in vitro bioassay for the larvae, the LC50 of the oil in liquid paraffin was 0.024%. A 10% solution was found to kill all immatures and more than 70% of adults feeding on rabbits. Rabbits were protected for 5 days against attaching larvae using a 10% solution. Preliminary experiments undertaken with cattle kept in the field suggest that the oil may have potential in tick control, and a role in integrated tick management.

From the whole plant extract of Daphne oleoides, two dimeric guaianolides seemarin and anabsinthin were isolated and characterized as new natural products. The structures of these lactones were determined by NMR spectral studies as well as by chemical methods.

Prostate cancer chemoprevention represents a relatively new and promising strategy for reducing the immense public health burden of this devastating cancer of men in the United States and Western societies. Chemoprevention is defined as the administration of agents (drugs, biologics, and natural products) that modulate (inhibit) one or more steps in the multistage carcinogenesis process culminating in invasive adenocarcinoma of the prostate. In 2000, there were an estimated 170,000 new cases of prostate cancer and 31,000 deaths in the United States. During the past decade, the National Cancer Institute (NCI) organized the chemoprevention research program and began testing the first generation of promising agents (eg, 4-(hydroxy)-fenretinide [4-HPR], difluoromethylornithine [DFMO], antiandrogens) in high-risk cohorts and launched the first-large scale US phase 3 primary prevention trial, known as Prostate Cancer Prevention Trial (PCPT-1), in 18,000 average-risk men (age more than 55 years and prostate-specific antigen [PSA] less than 3 ng/mL) treated for 7 years with finasteride or placebo. In the summer of 1998, the NCI Prostate Cancer Progress Review Group (PRG) Report to the director of NCI was published in response to the leadership of the prostate cancer advocacy community in conjunction with Congress. To further elucidate and address critical issues identified in this report and to develop a research agenda for the newly created Prostate and Urologic Cancer Research Group in the Division of Cancer Prevention at NCI, the NCI organized the workshop "New Clinical Trial Strategies for Prostate Cancer Chemoprevention." The major objectives were to promote understanding and cooperation among the NCI, US Food and Drug Administration (FDA), academia, pharmaceutical industry, and the public regarding new opportunities for clinical prevention trials for prostate cancer. The workshop was divided into three concurrent breakout panels and a fourth joint integrative panel. The workshop addressed multiple key areas identified in the PRG report in the following panels: (1) Molecular Targets and Promising Agents in Clinical Development; (2) Intermediate Endpoint Biomarkers for Prevention Trials; (3) High-Risk Study Populations for Prevention Trials, and (4) Preventive Clinical Trial Designs and Regulatory Issues. Expert panelists were drawn from leading academic, pharmaceutical, and government scientists in basic research and clinical investigation. Key pharmaceutical, biotechnology, academic, and National Institutes of Health scientists presented overviews of their new agents and products in clinical development (representing the next generation of promising agents). Senior FDA physicians from the Center for Drugs and Center for Biologics presented on current standards for new drug and biologic approval for chemoprevention efficacy. Some of the key topics included recent advances in the state of knowledge of promising agents in the clinic based on molecular targets as well as bottlenecks in drug development for pharmaceutical sponsors; strategic modulable biomarkers that can serve as primary endpoints in phase 1/2 trials to assess preventive efficacy; high-risk cohorts with precancer (high-grade prostatic intraepithelial neoplasia) and representative clinical trial designs that are ready for immediate translation into efficient prevention trials, such as Bayesian sequential monitoring for early assessment of biologic activity and factorial designs for assessment of multiagent combinations. Finally, each expert panel generated recommendations for areas of future research emphasizing opportunities and infrastructure needs.

Labdane diterpenes are an important class of natural products with a wide variety of biological properties. (−)-Limonidilactone is a labdane diterpene with a novel skeleton isolated from Vitex limonifolia. A new semi-synthetic route from andrographolide, the major constituent of Andrographis paniculata, has been described towards the synthesis of novel labdanes having a limonidilactone type skeleton.A facile synthetic route has been established to convert andrographolide 2 into two novel limonidilactone analogues 3 and 4.

Isatis tinctoria L. (woad) is a dye plant whose cultivation is increasing because of its adaptability to marginal conditions and increasing demand for natural products. Suitable breeding schemes need to be set up in order to obtain woad varieties for each proposed environment. Presently, no data about the reproductive system are available. The effects of selfing and crossing on setting and progeny vigour were assessed. Results showed the existence of an outcrossing system in I. tinctoria. Obligate self-pollinated plants produced fewer siliques (7.1 g per plant) with lower weight (6.0 mg) and lower seed germinability (8.2%) than outcrossing plants (44.1 g, 8.0 mg and 46.0% for each character, respectively). Self-pollinated progenies also generally showed lower vigour than outcrossing progenies.

We have previously obtained, by exposure to near continuous increas ing concentrations of cisplatin, a panel of human ovarian cancer cell lines that exhibit a wide range of primary resistance to the drug (9- to >400- fold). These cells had strikingly increased (4- to 50-fold) levels of gluta- thione (GSH) as compared with the drug-sensitive cells of origin (A. K.

Withaferin A (WA) is an important withanolide holding promise in cancer treatment and as a relatively safe radiosensitive/chemotherapeutic agent, which is present in traces in all parts of Withania somnifera except the leaves, where as it is reported to be present in only two non-Indian chemotypes (South African chemotype/Israel chemotype 1). The present studies have marked its presence in all Indian populations (wild/cultivated), as well as two identified Indian chemotypes (AGB002 and AGB025). The quantitative dynamics of WA production in Indian populations and interchemotypic hybrids developed at our institute have been studied, and the results were compared with five previously reported chemotypes from Israel, South Africa and India. An analysis on inheritance characteristics based on presence/absence of WA in hybrid plants and their respective parents is given for future studies on the chemogenetics of this complex species in greater detail. Further, the production potential of ...

Infection is the primary source of mortality in burn patients. One of the main treatment methods of burn wound infections is topical antimicrobial therapy, in which drugs have to permeate a dead tissue called eschar. Unfortunately, most antimicrobial agents can not permeate eschar in therapeutic levels. Surprisingly, permeation properties of this barrier and effects of chemical or environmental conditions on