Cytotoxic Terpene Quinones from Marine Sponges

The 1,4-benzoquinone moiety is a common structural feature in a large number of compounds that have received considerable attention owing to their broad spectrum of biological activities. The cytotoxic and antiproliferative properties of many natural sesquiterpene quinones and hydroquinones from sponges of the order Dictyoceratida, such as avarol, avarone, illimaquinone, nakijiquinone and bolinaquinone, offer promising opportunities for the development of new antitumor agents. The present review summarizes the structure and cytotoxicity of natural terpenequinones/hydroquinones and their bioactive analogues and derivatives

Antitumor Peptides from Marine Organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides

Synthetic Strategies to Terpene Quinones/Hydroquinones

The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described

MS

thesisMarine organisms produce a wide variety of metabolites that display diverse biological activities and represent an astonishing variety of molecular structural classes. As part of the Ireland group's continuing program to discover novel biologically active marine natural product, three sessile invertebrates from the Fijian and Philippine archipelagos were investigated. Isolation of the compounds described was directed to a large degree by the biological activities displayed by extracts and partitions of the organisms and was accomplished by using standard chromatographic techniques. The structures were solved using standard spectroscopic methods, including one-dimensional (1-D) and two-dimensional (2-D) nuclear magnetic resonance (NMR), infrared (IR) and ultraviolet (UV) spectroscopy, circular dischroism (CD), and low resolution and high resolution fast atom bombardment mass spectrometry (FABMS, HRFABMS). Mamanuthaquinone, a new member of class of quinine containing sesquiterpenoid compounds, was the major metabolite of the Fijian sponge Fasciospongia sp. Mamanuthaquinone is a potent cytotoxic agent with moderate antimicrobial activity. Chemical rearrangement was utilized to determine the absolute stereochemistry of mamanuthaquinone. An unidentifiable orange Fijian sponge of mixed taxonomy, having organizational and chemical characteristics of Axinellidae and Jaspidae families, yielded a new tetracyclic bromophyrrole derivative called epipolasidamide. Epipolasidamide exhibited in vitro cytotoxicity vs. HCT-116 cells, with IC50 of 0.1 mg/mL. Mild cytotoxicity exhibited by the crude extract of Philippino tunicate Eusynstyela misakiensis led to the isolation of eusynstyelamide, a novel dimer of a highly modified 6-bromotryptophan and decarboxylated arginine containing dipeptide. Eusynstyelamide was found to be mildly cytotoxic, with an IC50 of 50 mug/mL vs HCT-116 cells in vitro. The structure was determined by interpretation of 2-D NMR data, including HMBC and COSY45 data. A putative biosynthetic pathway for eusynstyelamide was developed, based on chemotaxonomic and structural evidence

A Markovian Decision Model for Deciding How Many Fire Companies to Dispatch

In deciding how many units to dispatch to an incoming alarm of unknown seventy the fire department is faced with a dilemma: If too few units are sent initially the extra units needed will be delayed; if too many units are sent, the extra units make a needless response and are temporarily unavailable for subsequent alarms. In this paper, we present a Markovian decision model for this problem. The model leads to a simple decision rule that considers three key factors: (1) the probability that the incoming alarm is serious (the greater the probability the more units dispatched); (2) the expected alarm rate in the area surrounding the alarm (the greater the alarm rate, the fewer units dispatched); and (3) the number of units available in the area surrounding the alarm (the more units available, the more units dispatched). We compare the decision rule to policies commonly in use and find that it results in significant improvements in response time to serious fires.government services: fire, probability: Markov decision models, simulation: use in policy analysis

An Integer Programming Model for Locating Vehicle Emissions Testing Stations

Connecticut and other states not in compliance with federal air quality standards are required to implement a motor vehicle inspection program to test vehicles for pollutants---hydrocarbons and carbon monoxide. The problem is to determine the number, size, and locations of stations given constraints on the maximum travel distance from each town to its nearest station and the average waiting time at a station. In this paper we use simulation to find the maximum allowable arrival rates (in vehicles per hour) of stations of different sizes and formulate the station location problem as a set covering model. We generate a range of solutions through sensitivity analysis, varying both the average waiting time and maximum distance constraints. Comparing the current configuration of stations in Connecticut to our integer programming solutions we find that the integer programming approach reduces the objective function by at least $3 million. The current configuration has more stations than the IP solutions but they are not as well distributed.optimal location, public facility location, integer programming location models, emissions testing stations location models

Chemical Insights into the Anchinopeptolide Series

International audienceThe chemical composition of the marine sponge Phorbas tenacior was investigated in depth. The anchinopeptolides A–D bearing a central pyrrolidinone were isolated together with a new congener named anchinopeptolide E corresponding to an epimer of anchinopeptolide C. The relative configuration of the central core of anchinopeptolide E was determined by extensive NMR analyses. Additionally, the previously isolated cyclobutane derivative cycloanchinopeptolide C was not detected from the sponge extract but could be synthesised by a photoinduced intramolecular [2+2] cycloaddition giving convincing evidence for its artefactual origin