Anti-Inflammatory Properties of Novel 1,2-Benzothiazine Derivatives and Their Interaction with Phospholipid Model Membranes.

The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics.

Interaction of meloxicam derivatives with phosphatidylcholine bilayers: A calorimetric study.

Background: The drug interactions with the lipid membranes are crucial in many biochemical processes. Phospholipid model membranes are often used to assess such interactions. Our team has been researching new compounds with anti-inflammatory and analgesic effects for many years.

New Meloxicam Derivatives-Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy.

The purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of the chemical structure, the studied compounds penetrated bilayers and affected mainly their polar/apolar regions, closer to the surface of the model membrane. The influence of meloxicam analogues on the thermotropic properties of DPPC bilayers was clearly visible because these compounds reduced the temperature and cooperativity of the main phospholipid phase transition.

Interactions of -Mannich Bases of Pyrrolo[3,4-]pyrrole with Artificial Models of Cell Membranes and Plasma Proteins, Evaluation of Anti-Inflammatory and Antioxidant Activity.

Despite the widespread and easy access to NSAIDs, effective and safe treatment of various inflammatory disorders is still a serious challenge because of the severe adverse effects distinctive to these drugs. The Mannich base derivatives of pyrrolo[3,4-]pyrrole are potent, preferential COX-2 inhibitors with a COX-2/COX-1 inhibitory ratio better than meloxicam. Therefore, we chose the six most promising molecules and subjected them to further in-depth research.

Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes-Calorimetric and Fluorescence Spectroscopic Study.

The modified 1,2-benzothiazine analogues designed as new drug candidates and discussed in this paper are oxicam derivatives. Oxicams are a class of non-steroidal anti-inflammatory drugs (NSAIDs). Their biological target is cyclooxygenase (COX), a membrane protein associated with the phospholipid bilayer.

Synthesis of New Tricyclic 1,2-Thiazine Derivatives with Anti-Inflammatory Activity.

New, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.

Non-Steroidal Anti-Inflammatory Drugs in Colorectal Cancer Chemoprevention.

Since colorectal cancer is one of the world's most common cancers, studies on its prevention and early diagnosis are an emerging area of clinical oncology these days. For this study, a review of randomized controlled, double-blind clinical trials of selected NSAIDs (aspirin, sulindac and celecoxib) in chemoprevention of colorectal cancer was conducted. The main molecular anticancer activity of NSAIDs is thought to be a suppression of prostaglandin E synthesis via cyclooxygenase-2 inhibition, which causes a decrease in tumor cell proliferation, angiogenesis, and increases apoptosis.

Synthesis and biological evaluation as well as in silico studies of arylpiperazine-1,2-benzothiazine derivatives as novel anti-inflammatory agents.

Novel arylpiperazine-1,2-benzothiazine derivatives have been designed and synthesized as potential anti-inflammatory agents. Their structure and properties have been studied using spectroscopic techniques (H NMR, C NMR, FT-IR), MS, elemental analyses, and single-crystal X-ray diffraction (SCXRD, for compound 7b). This study aimed to evaluate the inhibitory activity of new derivatives against both cyclooxygenase isoforms COX-1 and COX-2 due to the similarity of new compounds to oxicams drugs from the NSAIDs group.

Synthesis and pharmacological evaluation of novel arylpiperazine oxicams derivatives as potent analgesics without ulcerogenicity.

Gastrotoxicity continues to be a major issue in therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Medicine is yet to develop absolutely safe analgesics. Numerous strategies are employed to discover new, safer NSAIDs, for example selective inhibition of cyclooxygenase-2, new molecular targets (e.

Synthesis, COX-1/2 inhibition and antioxidant activities of new oxicam analogues designed as potential chemopreventive agents.

Oxicams (e.g. piroxicam, meloxicam) are widely used nonsteroidal anti-inflammatory drugs (NSAIDs).

The interaction of new oxicam derivatives with lipid bilayers as measured by calorimetry and fluorescence spectroscopy.

The purpose of the present work was to assess the ability of five new oxicam analogues to interact with the lipid bilayers. To characterize the interaction of newly synthesized NSAIDs (non-steroidal anti-inflammatory drugs) analogues with DPPC lipid bilayers the two following techniques were applied - differential scanning calorimetry (DSC) and fluorescence spectroscopy. The results obtained by these experimental approaches show that new oxicams analogues interact with the lipid model membranes under consideration.

Effect of new oxicam derivatives on efflux pumps overexpressed in resistant a human colorectal adenocarcinoma cell line.

Background: Oxicams are non-steroidal anti-inflammatory drugs (NSAIDs). Antitumor potential of NSAIDs has often been reported in literature. We studied antitumor activity of newly synthesized oxicam derivatives (PR17 and PR18) against doxorubicin-sensitive and resistant human colorectal adenocarcinoma cells (LoVo and LoVo/Dx).

The interaction of new piroxicam analogues with lipid bilayers--a calorimetric and fluorescence spectroscopic study.

The purpose of the present paper was to assess the ability of new piroxicam analogues to interact with the lipid bilayers. The results of calorimetric and fluorescence spectroscopic experiments of two new synthesized analogues of piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and fluorescence quenching of fluorescent probes (Laurdan and Prodan), which molecular location within membranes is known with certainty, are shown in present work. The presented results revealed that, depending on the details of chemical structure, the studied compounds penetrated the lipid bilayers.

Synthesis of new piroxicam derivatives and their influence on lipid bilayers.

A novel series of potentially biologically active 1,2-benzothiazine 1,1-dioxides--analogs of piroxicam (a recognized non-steroidal anti-inflammatory drug) were synthesized from commercially available saccharin. All of the synthesized compounds were subjected to preliminary evaluation for their ability to interact with lipid bilayers. The influence of the new derivatives of piroxicam on liposomes made of EYPC was investigated by fluorescence spectroscopy with two fluorescent probes--Laurdan and Prodan.

Giant unilamellar vesicles - a perfect tool to visualize phase separation and lipid rafts in model systems.

Model systems such as black lipid membranes or conventional uni- or multilamellar liposomes are commonly used to study membrane properties and structure. However, the construction and dimensions of these models excluded their direct optical microscopic observation. Since the introduction of the simple method of liposome electroformation in alternating electric field giant unilamellar vesicles (GUVs) have become an important model imitating biological membranes.

Genistein derivatives decrease liposome membrane integrity--calcein release and molecular modeling study.

The ability of newly synthesized genistein benzyl and glycosylated derivatives to permeabilize the liposome membrane was studied by calcein-leakage method. All studied derivatives appeared to be more effective than their parent compound--genistein. Comparing the experimental results with theoretical calculations we found that in the case of benzyl derivatives the dipole moment of added benzene ring (with its substitutions) might be important for the strength of flavonoids-lipid interactions.