Anti-Helicobacter pylori Activity of Isocoumarin Paepalantine: Morphological and Molecular Docking Analysis

Abstract

The Helicobacter pylori bacterium is one of the main causes of chronic gastritis, peptic ulcers, and even gastric cancer. It affects an average of half of the world population. Its difficult eradication depends upon multi-drug therapy. Since its classification as a group 1 carcinogenic by International Agency for Research on Cancer (IARC), the importance of H. pylori eradication has obtained a novel meaning. There is considerable interest in alternative therapies for the eradication of H. pylori using compounds from a wide range of natural products. In the present study, we investigated the antibacterial property of the isocoumarin paepalantine against H. pylori and it exhibited significant anti-H. pylori activity at a minimum inhibitory concentration (MIC) of 128 μg/mL and at a minimum bactericidal concentration (MBC) of 256 μg/mL. The scanning electron microscopy (SEM) revealed significant morphological changes of the bacterial cell as a response to a sub-MIC of paepalantine, suggesting a penicillin-binding protein (PBP) inhibition. Computational studies were carried out in order to study binding modes for paepalantine in PBP binding sites, exploring the active and allosteric sites. The data from the present study indicates that paepalantine exhibits significant anti-H. pylori activity, most likely by inhibiting membrane protein synthesis.

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

“…MiR-134 suppresses gastric carcinogenesis by targeting the KRAS gene and Golgi phosphoprotein 3 (GOLPH3) downregulation; another essential target gene of miR-134 is FoxM1 [200,201]. The inhibition of PBP via paepalantine is suggested to be a promising Cells 2020, 9, 1055 6 of 28 method of H. pylori activity decline [202]. Marcus et al showed that at pH 3.0, the expression of PBPs genes is significantly decreased [203].…”

Transformation of Helicobacter pylori into Coccoid Forms as a Challenge for Research Determining Activity of Antimicrobial Substances

“…In a set of eleven studies [45][46][47][48][49][50][51][52][53][54][55] determining an activity and morphological effect of plant extracts and plant-derived compounds on H. pylori, four of them reported a bacteriostatic activity [45][46][47][48] and six indicated a bactericidal effect [49][50][51][52][53][54] of the tested compounds. In one case, the use of this classification was avoided [55].…”

“…The six studies indicated the bactericidal effect of the tested compounds on H. pylori [49][50][51][52][53][54]. A capacity to completely inhibit growth was only proven in half of them [49,51,52], which was achieved in a range of 18 h [49] to 72 h [51] with MICs. A relationship between the decrease in viability and number of spherical forms was particularly well illustrated in the Lee et al article [51].…”

Nanohybrid-based immunosensor prepared for Helicobacter pylori BabA antigen detection through immobilized antibody assembly with @ Pdnano/rGO/PEDOT sensing platform

“…Helicobacter pylori ( H. pylori ) prevalence in hosts contributes to chronic gastritis and gastric cancer. Gram-negative bacterium is the type of H. pylori that ultimately leads to the progression of ulcers and cancer by infecting the gastric mucosa 1 – 3 . H. pylori develops mechanisms for gastric colonization with the help of virulence factors, causes gastric ulceration and plays a major role in the progression of stomach cancer.…”