Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation

Gupta, Ashutosh; Shetty, Shiran; Mutalik, Srinivas; Chandrashekar H, Raghu; K, Nandakumar; Mathew, Elizabeth Mary; Jha, Abhishek; Mishra, Brahmeshwar; Rajpurohit, Siddheesh; Ravi, Gundawar; Saha, Moumita; Moorkoth, Sudheer

doi:10.1016/j.heliyon.2023.e20406

Cited by 20 publications

(8 citation statements)

References 157 publications

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“…Although compounds 5b and 7e are the lead inhibitors of urease in this research, their gastrointestinal absorption determined by in silico analysis needs to be limited. This can be reduced by selecting the best drug delivery system, such as nanoparticles ( Gupta et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Akash,

Zaib,

Ahmad

et al. 2024

Front. Chem.

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Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of −8.0 (5b) and −8.1 (7e) kcal/mol. The binding energy of thiourea was −2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and −6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

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Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Akash,

Zaib,

Ahmad

et al. 2024

Front. Chem.

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“…According to Lee and Park, the 90% effectiveness rate of clarithromycin-based triple therapy has now dropped to 70–80%. An alternative treatment option for resistance to clarithromycin-based therapy is bismuth-based quadruple therapy [ 117 , 118 ]. A second-line therapy is administered if the first treatment fails and, normally, levofloxacin (or moxifloxacin), amoxicillin, a PPI triple regimen, and bismuth-containing quadruple therapy are used [ 119 ].…”

Section: Selected Paediatric Infectious Diseasesmentioning

confidence: 99%

“…A second-line therapy is administered if the first treatment fails and, normally, levofloxacin (or moxifloxacin), amoxicillin, a PPI triple regimen, and bismuth-containing quadruple therapy are used [ 119 ]. The evaluation of regimens using fluoroquinolones, including levofloxacin, as second-line therapy in children is limited due to their side-effects in those less than 14 years old [ 118 , 120 ].…”

Section: Selected Paediatric Infectious Diseasesmentioning

confidence: 99%

“…Different bacterial pathogens have different adaptive mechanisms that allow them to survive the gastric acid, move, and migrate to form biofilms which, in turn, create a barrier for antimicrobial penetration. This is particularly evident in gastrointestinal diseases giardiasis, Helicobacter pylori , and Clostridioides difficile [ 118 , 208 , 209 ]. Consequently, it can lead to an increase in bacterial load [ 210 ].…”

Section: Currents Trends and Gapsmentioning

confidence: 99%

“…Another gastroretentive delivery approach that has been gaining attention for the encapsulation of anti-infectives covered herein is the application of magnetic systems which can control the movement of a gastroretentive formulation with a small internal magnet by applying a strong magnetic field onto the body surface. Numerous studies highlight the system’s benefits, but the magnet position must be chosen with extreme precision for the system to work [ 244 ], and gastroretention may be impacted by the extracorporeal magnet’s intensity [ 118 ]. For instance, Abdelaziz and colleagues created vancomycin-conjugated magnetic nanoparticles with specific antibacterial activity by employing a straightforward conjugation technique [ 245 ].…”

Section: Currents Trends and Gapsmentioning

confidence: 99%

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Leading Paediatric Infectious Diseases—Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions

Rampedi,

Ogunrombi,

Adeleke

2024

Pharmaceutics

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Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

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Development of Novel Hydroxy Amide‐Based HDAC1 Inhibitors: Integrated Pharmacophore Modelling, 3D‐QSAR, and Virtual Screening Studies

Saha,

Gupta,

Gupta

et al. 2024

ChemistrySelect

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Histone deacetylases (HDAC) are well‐established epigenetic targets for cancer therapy, with several HDAC inhibitors already approved for clinical use. Despite their potential, the clinical application of HDAC inhibitors, particularly HDAC1‐selective compounds, faces significant challenges. These include poor pharmacokinetics, limited bioavailability, and a lack of selectivity, which often necessitates to combine these inhibitors with other drugs for improved efficacy. Their limitations as standalone therapies emphasize the urgent need for further research and development. In this study, the dataset of 71 compounds were used to generate various pharmacophore models, among them DDRRR_1 was generated as the best pharmacophore model with a survival score of 6.148. The 3D‐QSAR data of theses compound showed a significant result with the values of R2 = 0.95 and Q2 = 0.87 in the atom‐based model and R2 = 0.901 and Q2 = 0.77 in the field‐based model. R‐group enumeration study generated novel 6426 compounds which was further screened through virtual screening study. The top‐scoring compound was M1 with the highest docking score (−8.804 kcal/mol) where hydroxy amide is important for interaction with HDAC1 protein. The ADME analysis demonstrated the compound's drug‐like characteristics. Overall, all hit compounds showed pharmacokinetic characteristics found within the range that is considered safe for human usage. This study findings have the potential to be applied further in the development of HDAC1 inhibitors for the treatment of gastric cancer.

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Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation

Cited by 20 publications

References 157 publications

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Leading Paediatric Infectious Diseases—Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions

Development of Novel Hydroxy Amide‐Based HDAC1 Inhibitors: Integrated Pharmacophore Modelling, 3D‐QSAR, and Virtual Screening Studies

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