In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors.

Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. METHODS: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. RESULTS: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca2+ channel regulation, Ca2+ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. CONCLUSION: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS.

Liquid-phase combinatorial library synthesis: recent advances and future perspectives.

Liquid-phase combinatorial library synthesis is commonly developed into the viable alternatives or adjunct across the broad spectrum of polymer-supported organic chemistry. It includes the use of soluble polymer supports in the combinatorial synthesis of peptides and small-molecular library compounds which act as catalyst and reagent supports. It also includes high throughput biological screening with generation and evaluation of chemical leads for drug discovery development. In this review, liquid-phase combinatorial library synthesis is shown as the most efficient method of choice for the synthesis of most of the combinatorial library compounds with specific approaches from different groups that state potentials of solution-phase combinatorial synthesis.

Benzopyran derivatives as cardio-selective ATP-sensitive potassium channel openers: a review.

Benzopyran derivatives are the potassium channel openers (KCOs) having antihypertensive, cardio-protective, myocardial protectors, powerful peripheral vasodilators and anti-ischemic activity. Their usage as anti-ischemic including angina, hypertension and diabetes is thought to be due to the stimulation of KATP channels which are contemplated to produce vasorelaxation and myocardial protection. It is observed that potassium channels are involved in mediating the cardio-protective effects of pre-conditioning in animal models and man. KCOs protect heart from an ischemic insult without contribution from vasodilatation. This review provides an overview of the characteristics of KCOs and their actions on subtypes used widely for the treatments of various diseases including hypertension, cardiac ischemia, arrhythmia, smooth muscle relaxation, diabetes, cardio-protective and anti-angiogenic activities.

Novel anticancer agents and targets: recent advances and future perspectives.

An urgent need for the discovery of novel anticancer agents is required for the long term therapy of cancer. Large number of novel bio-active and potential anticancer agents are being used in clinical and pre-clinical trials. Although many heterocyclic compounds are already available commercially as anticancer agents, great efforts have been put to identify novel anticancer targets. This review provides an insight of the novel anticancer targets and molecules of the first and final stage of clinical and pre-clinical trials.

Silica-supported polyphosphoric acid in the synthesis of 4-substituted tetrahydroisoquinoline derivatives.

We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides. We compared the cyclisation step using conventional (milieu of acetic-trifluoracetic acid = 4:1) and solid supported reagents (SiO2/PPA), as recovered, regenerated and reused without loss of its activity catalyst. We found that in comparison to conventional methods, the yields of the reaction are greater and the reaction time is shorter.