Membrane-based conceptual design of reuse water production from candy factory wastewater.

Intense pressure on water resources has led to efforts to reuse reclaimed processing wastewater in the food industry. There are tight rules for water quality, but efficient separation technologies such as reverse osmosis possess good possibilities for water reuse. This study developed a membrane-based reuse water concept for wastewater from the candy industry emphasizing the pre-treatment stage in the concept to reduce fouling. The wastewater contained suspended solids, sugar compounds and the ingredients for candy gelation, which had a tendency to foul membranes, making pre-treatment essential for a successful concept. Cross-rotational ultrafiltration, which featured enhanced fouling prevention for membranes, functioned well for the removal of challenging substances. Conventional filtration technologies were impractical due to a low flux, even when the viscosity of the wastewater was reduced using surfactants. The wastewater had a high chemical oxygen demand, meaning that there was a strong fouling potential for reverse osmosis membranes, but also high osmotic pressure. A spiral wound reverse osmosis functioned well when the wastewater was pre-treated, and it produced good quality water with respect to all the other studied parameters except the chemical oxygen demand. However, chemical oxygen demand rejection was 99% since the concentration in the wastewater was originally very high.

Building a MCHR1 homology model provides insight into the receptor-antagonist contacts that are important for the development of new anti-obesity agents.

Melanin-concentrating hormone (MCH) regulates feeding and energy homeostasis through interaction with its receptor, the melanin-concentrating receptor 1 (MCHR1), making it a target in the treatment of obesity. Molecular modeling and docking studies were performed in order to find a binding model for the docking of two new series of MCHR1 antagonists to the receptor. Results suggested interactions between the ligands and two glutamines (Gln5.42 and Gln6.55) not conserved in many of the GPCRs family members. Histamine 3 receptor (HRH3) presents two apolar residues in the aforementioned positions and the available biological data against this receptor supported the role of the two glutamines in the binding of antagonists to the MCHR1. This knowledge could be useful in the development of new, more active and more selective MCHR1 antagonists.

Melanin-concentrating hormone receptor 1 antagonists: a new perspective for the pharmacologic treatment of obesity.

Obesity is a chronic disease characterized by the accumulation of excess adipose tissue associated with an increased risk of multiple morbidities and mortality. At the present time, only three drugs have been approved by the Food and Drug Administration (FDA) for the treatment of obesity. Agonists and antagonists of some of the substances implicated in the regulation of energy homeostasis represent opportunities for anti-obesity drug development. The most promising targets are alpha-melanocyte stimulating hormone (alpha-MSH) receptors, cannabinoid receptors, the 5-hydroxytryptamine (5-HT) receptors and melanin-concentrating hormone (MCH) receptors. MCH receptors could be major potential targets for the treatment of obesity. Many pharmaceutical companies have described MCH-R1 antagonists that have appeared over the past year. Recently, two compounds went into phase I clinical trials that evaluate MCH receptor antagonists as a new perspective for the pharmacologic treatment of obesity. In this review, structure-activity relationships (SAR) in the development of MCH-R1 antagonists are provided.

Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies.

The combination of antagonism at histamine H(3) receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H(3) receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H(3) antagonism affinity. However, since all these derivatives failed to block K(ATP) channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H(3) antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype.

New amide derivatives as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity.

Melanin-concentrating hormone (MCH) is a recently discovered central nervous system (CNS) target for treating obesity. Two novel series of amide derivatives were synthesized and evaluated biologically as MCH-R1 (melanin-concentrating hormone receptor 1) antagonists. The results showed that diphenyl substituents on the amide lead to better activity than biphenyl substituents.

Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity.

We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3'-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM K(i).