Novel approaches to the control of infectious diseases

As part of our ongoing efforts to find new drug leads against infectious diseases, several terrestrial and marine macro- and microorganisms were investigated. Several bioactive molecules, presented below, were isolated from these natural products. The mass-screening of dozens of marine Actinomycetes was completed and several Streptomyces with interesting biological activity profiles identified. A few examples are the Streptomyces code H747 and the Streptomyces code H668, a bacterium from which a new (5) and two known polyethers, the antimalarial agent K41-A (6) and its C-29 analog (7) were isolated. Five new six-membered ring cyclic peroxides: plakinastreloic acid A (8), methyl plakinastreloate A (9), the C-12 epimers of methyl 13, 14-epoxyplakinastreloate (10 & 11), and plakinastreloic acid B (12) were isolated from a marine sponge of the genus Plakinastrella. Compounds 8 and 9 exhibited antifungal activities against Candida albicans (IC50 = 6.5 µg/mL and 3.5 µg/mL, respectively), Aspergillus fumigatus (IC50 = 4.0 µg/mL and 9.0 µg/mL, respectively) and Cryptococcus neoformans (IC50 = 4.0 µg/mL and 9.0 µg/mL, respectively). A moderate antimalarial activity against CQ-resistant and CQ-sensitive strains of Plasmodium falciparum was observed, as well. It was also established that 8 possesses anti-HCV (Hepatitis C Virus) activity. Two other compounds were isolated from HCV active methanol extracts of Inga fagifiolia (twigs) and Diplostephium rhodendroides (leaves). These compounds were identified as 2,3,4,5,6-pentahydroxy-2-(hydroxymethyl)hexanamide (14), the amide of a known molecule and 4,5-dihydroxy-3-[(3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy] pentanoic acid (15). The bioassay-guided approach used for their isolation and structure elucidation is reported here. The potential of scCO2 to inactivate bacteria trapped in the gut of oysters was studied. It was established that exposing oysters to CO2 at 100 bar and 37 °C for 30 minutes and at 172 bar and 60 °C for 60 minutes induced 2-log and 3-log reductions in the APC loads, respectively. The decrease in the microbial load as a result of treatment with scCO2 was found to be significant (P = 0.002). A blind study allowing sensory analysis of treated vs. untreated oysters was also completed; no significant difference in the physical appearance, smell, or texture was recorded

Cytotoxicity and antiproliferative effects of extracts from coffee cherry fruit on cell lines from normal breast tissue and from non-invasive and invasive breast cancers

Thesis (M.S.)--University of Hawaii at Manoa, 2005.Includes bibliographical references (leaves 106-109).xxi, 109 leaves, bound ill. (some col.) 29 c

Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

BACKGROUND: As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. OBJECTIVE: Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. CONCLUSION: Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics

Eating oysters without risk of vibriosis: Application of a bacteriophage against Vibrio parahaemolyticus in oysters

Vibrio parahaemolyticus is a major cause of foodborne illness and related with the consumption of raw contaminated seafood, especially oysters. To evaluate the effectiveness of various applications of a bacteriophage (phage), pVp-1, against a multiple-antibiotic-resistant V. parahaemolyticus pandemic strain (CRS 09-17), we designed artificial contamination models that are most likely to be encountered during oyster processing. When live oysters were treated with bath immersion with pVp-1 after CRS 09-17 challenge, the growth of bacterial strain was significantly reduced. After 72 h of phage application with bath immersion, bacterial growth reduction was observed to be 8.9 x 10(6) CFU/ml (control group) to 1.4 x 10 CFU/ml (treatment group). When pVp-1 was surface-applied on the flesh of oysters after CRS 09-17 inoculation, bacterial growth was properly inhibited. After 12 h of phage application on the surface of oysters, bacterial growth inhibition was revealed to be 1.44 x 10(6) CFU/ml (control group) to 1.94 CPU/ml (treatment group). This is the first report, to the best of our knowledge, of oyster surface-application of a phage against a multiple-antibiotic-resistant V. parahaemolyticus pandemic strain, and our successful phage application to various situations emphasizes the potential use of the phage to avoid V. parahaemolyticus infection from aquaculture to consumption. (C) 2014 Elsevier B.V. All rights reserved.N

Quality Performance Assessment of Gas Injection During Juice Processing and Conventional Preservation Technologies

International audienceDespite the numerous processes proposed as alternatives to heat pasteurization, thermally treated juices produced by full or flash pasteurization are still the most widely marketed product. It is well known that the flavor of fruit juices is influenced by heat treatment used for microbial stabilization; as an example, volatile compounds, such as alpha-terpineol and the terpinen-4-ol synthesized during heat treatments are responsible for the “oxidized” and “cooked” flavors of the orange juice. In addition, between the setting out of bottle and the consumption of the fruit juice, it can occur several days even several weeks. Food is subjected to the laws of aging and chemical additives are often used to stabilize fruit drinks, and in such an objective, gases may offer new perspectives; in this chapter the use of oxygen, nitrogen, carbon dioxide, and hydrogen are investigated