Thioxanthene-derived analogs as sigma(1) receptor ligands

An investigation of the structure-affinity relationships for the binding of thioxanthene-related structures indicates that an intact thioxanthene ring is not required for binding at sigma(1) receptors, and that with the appropriate structural modifications, affinity can be enhanced to the subnanomolar level. Certain of the analogs displayed sigma(1)-fold selectivity for sigma(1) versus sigma(2) receptors.     

Design and synthesis of some thiazolyl and thiadiazolyl derivatives of antipyrine as potential non-acidic anti-inflammatory,analgesic and antimicrobial agents

The synthesis of two groups of structure hybrids comprising basically the antipyrine moiety attached to either polysubstituted thiazole or 2,5-disubstituted-1,3,4-thiadiazole counterparts through various linkages is described. Twelve out of the newly synthesized compounds were evaluated for their anti-inflammatory activity using two different screening protocols; namely, the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays, using diclofenac Na as a reference standard. The ulcerogenic effects and acute toxicity (ALD₅₀) values of these compounds were also determined. Meanwhile, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. Additionally, the synthesized compounds were evaluated for their in vitro antimicrobial activity. In general, compounds belonging to the thiazolylantipyrine series exhibited better biological activities than their thiadiazolyl structure variants. Collectively, compounds 6, 10, 26, and 27 proved to display distinctive anti-inflammatory and analgesic profiles with a fast onset of action. All of the tested compounds revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD₅₀ > 3.0 g/kg). Meanwhile, compounds 7, 10, 11, and 23 are considered to be the most active broad spectrum antimicrobial members in this study. Compound 10 could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory analgesic and antibacterial profile.     

Synthesis and biological evaluation of novel pyrazole compounds

A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2.     

Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents

Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds were further studied in vivo by using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays. We identified four novel compounds that showed protective effects in vitro at non-toxic concentrations, and were also effective in the animal models of acute and sub-acute inflammation.     

Salvia officinalis L. Methanolic Extract Reduces Lead and Nicotine-Induced Sperm Quality Degeneration in Male Rats

Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220–250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats’ sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats’ fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.     

Activation of EMT in colorectal cancer by MTDH/NF-κB p65 pathway

Molecular and Cellular Biochemistry - Epithelial-mesenchymal transition (EMT) leads to tumor dissemination and metastasis. Metadherin (MTDH) is an oncogene that plays an important role in...