Том 25, № 18 (2025)
- Жылы: 2025
- Мақалалар: 2
- URL: https://kld-journal.fedlab.ru/1871-5206/issue/view/14213
Chemistry
Evaluation of the cagA, dupA, sabA, babA, and iceA1 Gene Expressions in H. pylori Strains Isolated from Patients with Gastric Cancer and Peptic Ulcer Disease
Аннотация
Background: Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting almost half of the population of the world. Some specific virulence genes of this bacterium have a significant causal effect on the outcome of gastrointestinal diseases. Therefore, the aim of this study was to evaluate the expressions of the cagA, dupA, sabA, babA, and iceA1 genes of H. pylori cultured from biopsy specimens of patients with GC and PUD and to compare these expressions with those in NUD patients as the control group.
Methods: The patients with gastrointestinal disorders referred to Shahid-Beheshti Hospital in Qom, Iran, were enrolled in this study. Eleven biopsies per patient were collected and used for culture, pathology, and rapid urease tests. Based on endoscopic and pathological findings, patients were separated into three groups: GC, PUD, and NUD. Colonies suspected of H. pylori were initially investigated using conventional evaluations and then confirmed by PCR assay. Also, the RT-qPCR method was used to evaluate the expression of target genes, including cagA, dupA, sabA, babA, and iceA1 in isolated strains.
Results: One hundred and seventy-seven patients, including 31 GC, 55 PUD, and 91 NUD, were included in this study. Among the enrolled patients, 29 patients were positive for H. pylori based on three evaluation methods. The expression of bacterial cagA, dupA, and babA genes in the GC patients was statistically higher than in the NUD group. The expression of the sabA gene in the strain isolated from the GC group was lower than in the control group. No significant difference was observed between the GC group and the control group regarding the iceA1 gene.
Conclusion: Our finding shows that the expressions of cagA, dupA, and babA virulence genes in H. pylori strains isolated from gastric biopsies of both GC and PUD patients are significantly higher than the NUD ones. Therefore, screening and treating the infection caused by this bacterium and determining the genotype in patients may prevent the progression of the disease.
1420-1428
Design and Synthesis of 2-substituted [1,2,4]Triazolo[1,5-a]pyrimidines Tethered with Umbelliferone as Selective Carbonic Anhydrase IX and XII Inhibitors
Аннотация
Objective: This study presents the design and synthesis of a new series of human carbonic anhydrase (hCA) inhibitors based on a 5-methyl/phenyl-7-(7’-oxycoumarin)-[1,2,4]triazolo[1,5-a]pyrimidine scaffold.
Methods: The chemical structures of novel coumarin-based triazolopyrimidines 3a-u were confirmed after using NMR and MS analyses. Their inhibitory profiles were evaluated against a panel of five hCA isoforms. Molecular docking simulations were conducted to elucidate the binding modes of compounds 3d and 3s with hCA IX and XII isoforms. Selected derivatives 3d and 3g were tested for their antiproliferative effects on the medulloblastoma HD-MB03 and the glioblastoma U87MG cell lines. Additionally, compounds 3d and 3g were evaluated alone or in combination with cisplatin (cis-Pt) for their ability to induce apoptosis in HD-MB03 cells.
Results: In vitro kinetic studies demonstrated that all 5-methyl triazolopyrimidine derivatives (3a-r) selectively inhibited the tumor-associated hCA isoforms (hCA IX and XII), with KI values ranging from 0.75 to 10.5 μM, while hCA I, II, IV isoforms were not significantly inhibited (KIs > 100 μM). Compound 3d emerged as the most potent and selective inhibitor, with KIs of 0.92 and 0.75 μM for hCA IX and XII, respectively. This derivative significantly suppressed cell proliferation in human brain tumor cell lines, particularly HD-MB03, when it was studied for its adjuvant effects in combination with cisplatin.
Conclusion: In this study, we have identified compound 3d as a selective inhibitor of the isoforms hCA IX and XII, showing minimal inhibition over hCA I, II, and IV isoenzymes (selectivity indices > 100). Its moderate inhibitory effects on hCA IX and XII at submicromolar levels were paralleled by significant antiproliferative activity against HD-MB03 cells. These findings underscore the potential of compound 3d as a promising candidate for further therapeutic development, especially in combination with clinically used chemotherapeutic agents.
1429-1446