Predictive Value of Individual Gastric Secretion Indices and Their Constellations for Predicting the Response of Gastric Mucosal Parietal Cells to Pentagastrin Stimulation and Famotidine Blocking Effect in Patients with Gastric and Duodenal Ulcers

UDC: 616.33/.342–002.446–018.73:612.32]–085.243]–037

Introduction. Evaluating acid-reducing medications through their effect on various gastric juice parameters in peptic ulcer patients provides deeper insight into the complex mechanism of gastric secretion, which includes acidity levels, pepsin, electrolytes, bicarbonates, and mucus.

The aim of the study. To determine the prognostic value of gastric secretion parameters and their constellations for predicting parietal cell response to submaximal pentagastrin stimulation and the blocking effect of famotidine in patients with gastric and duodenal peptic ulcer disease.

Materials and methods. The study included 40 randomized Helicobacter pylori-positive patients (28 women, 12 men, aged 18-68) with endoscopically confirmed duodenal ulcer disease in the acute phase. Modified fractional probing was used to assess changes in gastric secretion.

Results. H+ debit in basal secretion showed a significant direct correlation with multiple parameters. Different acid responses to stimulation were associated with specific baseline parameter constellations. Weak response to H2-blocker was confirmed in patients with hyperacidity after stimulation, combined with elevated HCl and increased total acidity in basal secretion. A strong response to H2-blocker was confirmed in several parameter constellations, with the best predictive constellation (p < 0.01) including elevated N-acetylneuraminic acid, normal K+, normal pepsin debit, normal pepsin, and elevated Na+ in basal secretion.

Conclusions. The prognostic value of gastric secretion parameters and their constellations allows tailoring blocker dosage: higher doses for patients predicted to have a weak response and lower doses for those predicted to have a strong response to stimulation.


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Synthesis and biological activity of rhodanine-furan conjugates: A review.

Rhodanines are recognized as privileged heterocycles in medicinal chemistry. The main achievements include the development of drug-like molecules with numerous biological activities as well as approved drugs. The Furan nucleus is considered one of the promising heterocyclic cores in medicinal chemistry that showed numerous ranges of activity. The combination of several heterocycles in a one molecule commonly provides much more interest in the enhanced activity profile of its analogs than their parent separate constituents. Such conjugates are promising objects for modern medicinal chemistry. In this review paper recent advances in the synthesis and biological activities rhodanine-furan conjugates which its application in the different field of drug discovery.

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Synthesis, analysis adme-tox parameters and anti-cancer activity of n-(5-r-benzylthiazole-2-yl)-2-morpholin-4-yl-2-thioxoacetamides

Aim. Study of the synthesis, analysis of ADME - Tox parameters and anti-cancer activity of a series of N-(5-R-benzylthiazole-2-yl)-2-morpholin-4-yl-2-thioxoacetamides.
Methods. Organic synthesis, 1H NMR spectroscopy, analytical method, in silico ADME-Tox analysis and in vitro cytotoxicity assay.
Results. The series of new N-(5-R-benzylthiazole-2-yl)-2-morpholin-4-yl-2-thioxoacetamides was synthesized according to a convenient synthetic method. Their structures were confirmed by 1H NMR spectroscopy and microanalyses. Using the internet resources of SwissADME and pkCSM-pharmacokinetics, the ADME - Tox profiles of the synthesized compounds were calculated. It was determined that the substances were within the optimal limits of  bioavailability. All compounds meet the criteria of drug similarity according to the rules of Lipinski, Weber, Egan and Mugge. It is also determined that low toxicity is predicted for these substances. The synthesized compounds were tested in vitro for their antitumor activity according to the Developmental Therapeutic Program of the National Cancer Institute (NCI) (www.dtp.nci.nih.gov) against 60 cancer lines in the concentration of 10 μM. Human tumor
cell lines from nine different cancer types were used: leukemia, melanoma, lung, colon, CNS, ovarian, kidney, prostate an d breast cancer. Screening results showed that, in most cases, these compounds are of low activity. An exception is the renal cancer line UO-31, which was moderately sensitive to all synthesized compounds.
Conclusions. A series of 2-aminothiazole hybrids containing morpholine moiety was synthesized and studied in silico ADME-Tox profiles. The ADME-Tox profiles indicated good oral bioavailability and low toxicity. Synthesized compounds were tested in vitro for their anti-cancer activity. They showed moderate antiproliferative activity.
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Current trends of chemoinformatics and computer chemistry in drug design: A review.

A crucial direction in the progress of modern medical chemistry is the development and improvement of theoretical investigation methods of drugs mechanisms of action, predicting their activity, and virtual design of new drugs. This review describes the history of targeted search for biologically active compounds, current in silico approaches and tools used in the rational design of potential drugs, in particular the main computational strategies used in modern drug design are presented and outlines the main methodologies for implementing these strategies. 

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