Aspects of molecular medicine最新文献

{"title":"In-silico identification of phytochemicals as potential therapeutic agents to inhibit the HMG-CoA reductase activity using computational approach","authors":"Sheetal Dagar ,&nbsp;Anil Panwar ,&nbsp;Dushyant Gahalyan ,&nbsp;Neeru Redhu ,&nbsp;Mukesh Kumar ,&nbsp;Sunil Kumar ,&nbsp;Varruchi Sharma ,&nbsp;Heera Ram ,&nbsp;Ravikant Verma ,&nbsp;Anil Sharma","doi":"10.1016/j.amolm.2025.100086","DOIUrl":"10.1016/j.amolm.2025.100086","url":null,"abstract":"<div><div>Phytochemicals, have long been studied for various severe metabolic illnesses and degenerative diseases like heart disease and cancer because of their significant therapeutic effects. In animal cells, cholesterol serves a critical role being a component of cell membranes and essential for the normal functioning of precursor cells to some steroid hormones. Three-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) is converted into mevalonate by the HMG-CoA Reductase (HMGCR) enzyme to produce cholesterol. However, when cholesterol levels are high, it may result in atherosclerosis. Statins, also known as synthetic drugs which decrease cholesterol, are therefore designed to work by targeting this enzyme. For patients with dyslipidemia, the side effects of excessive statin therapy have proven alarming hence using natural plant-based inhibitors is a promising alternative. Computational approach helps to identified many drugs that can target HMG-CO A Reductase. In this study, using <em>in-silico</em> molecular docking via auto-dock, 20 medicinal plants with 120 phytochemicals, reported as having antihyperlipidemic activity through deep literature study, were screened as HMG-CoA reductase enzyme inhibitors. The virtual molecular docking results reveals that five bioactive compounds; Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol, had higher binding affinities towards the HMG-CO A Reductase having binding energies of −9.33, −8.99, −8.87, −8.58, and −8.48 kcal/mol, respectively. ADMET properties of selected compounds were analysed using swiss adme tool. Results showed that out of five compounds three follow Lipinski rule of five, having ADMET properties. The HMG-CoA reductase-ligand complex's stability was validated by RMSD, RMSF, Rg, H-bond results and principal component analysis. The resulting trajectories of converged period of MD were further exploited in MM-P/G/BSA calculations to derive accurate estimates of binding free energies. This leads one to the conclusion that five phytochemicals, Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol can serve as potential inhibitors in regulating HMGCR's function may assist the development of effective anti-hyperlipedemic drugs.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico identification of potential inhibitors for the universal stress G4LZI3 protein from Schistosoma mansoni using molecular docking and molecular dynamics simulation analyses","authors":"Lihle Mahamba,&nbsp;Mustafa Alhaji Isa,&nbsp;Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100084","DOIUrl":"10.1016/j.amolm.2025.100084","url":null,"abstract":"<div><div><em>Human schistosomiasis</em> is a debilitating, neglected tropical disease affecting millions worldwide. Control efforts primarily rely on health education, improved sanitation, snail host management, and mass drug administration with Praziquantel (PZQ). PZQ has some limitations, such as its lower effectiveness against immature parasites and the potential for developing resistance. This requires the urgent need for new treatment approaches. The universal stress protein G4LZI3 helps the <em>Schistosoma mansoni</em> parasite survive when it is under stress from its host. Because of this, it emerges as a promising target for developing new drugs. Despite its biological relevance, G4LZI3 has not been previously investigated as a druggable target, highlighting a significant research gap in schistosomiasis drug discovery. To find potential inhibitors of G4LZI3, we conducted a virtual screening using the RASPD⁺ tool, which led us to select 7889 ligands from the CoCoNut database. These ligands were filtered based on physicochemical properties (Lipinski's Rule of Five, Veber's Rule, Egan's Filter, and the Ghose filter), pharmacokinetics, and Pan-Assay Interference Structures (PAINS) criteria, followed by molecular docking. Fifteen compounds demonstrated strong binding affinities, with binding energies ranging from −10.6 to −8.50 kcal/mol, exceeding that of PZQ (−8.4 kcal/mol). From these, six compounds were selected for further analysis, including molecular dynamics (MD) simulation, solvent-accessible surface area (SASA), and molecular mechanics generalized Born surface area (MM-GBSA) calculations. MD simulation of 200 ns revealed that CNP0475438, CNP0415153, and CNP0353858 achieved significant stability and favourable interactions with G4LZI3. These findings show these compounds as promising candidates for <em>S. mansoni</em> inhibition, pending experimental validation. The results identify novel scaffolds with vigorous predicted activity and provide a rational starting point for experimental optimization and development of new antiparasitic therapies that address praziquantel resistance and efficacy limitations in endemic regions.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and exploration of novel FGFR-1 inhibitors in the Lotus database for Cholangiocarcinoma (CCA) treatment","authors":"Samuel Aduramurewa Osunnaya ,&nbsp;Wilberforce K. Ndarawit ,&nbsp;Ifeoluwa Aderibigbe ,&nbsp;Ibilola A. Omolopo ,&nbsp;Precious O. Aribisala ,&nbsp;Ayodele Oluwasegun Elekan ,&nbsp;Adeola Sakirat Adeyemo ,&nbsp;Sheriffdeen Abiola Amoo ,&nbsp;Olatunde Simbiat Olamiposi ,&nbsp;Njogu M. Kimani ,&nbsp;Taiwo Hamidat Olaide ,&nbsp;Adedoyin John-Joy Owolade ,&nbsp;Damilola Samuel Bodun","doi":"10.1016/j.amolm.2025.100085","DOIUrl":"10.1016/j.amolm.2025.100085","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a rare but aggressive cancer affecting the bile duct, with limited treatment options and a poor prognosis. This study employed a machine learning algorithm and molecular docking using Maestro to screen 215,925 compounds from the Lotus database, aiming to identify potential fibroblast growth factor receptor-1 (FGFR1) inhibitors as therapeutic agents. Five promising compounds were identified, with binding energies ranging from −10.018 to −8.439 kcal/mol, all outperforming the standard drug Dovitinib (−8.419 kcal/mol). Molecular mechanics calculations and MM/GBSA analysis confirmed the structural stability and favorable binding energies of the protein-ligand complexes. Additionally, 100-ns molecular dynamic simulations demonstrated that the top three compounds remained stable within FGFR1's active site, supported by root mean square deviation, root mean square fluctuation, and hydrogen bond interactions. Overall, these five compounds show promise as potential therapeutic agents for CCA and warrant further investigation for drug development.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective potential of vanillic acid against isoniazid-rifampicin-induced liver toxicity","authors":"Mohd Islam Ansari,&nbsp;Nazneen Dubey,&nbsp;Aditya Ganeshpurkar","doi":"10.1016/j.amolm.2025.100087","DOIUrl":"10.1016/j.amolm.2025.100087","url":null,"abstract":"<div><div>Liver toxicity induced by antitubercular drugs, such as isoniazid and rifampicin, poses a significant clinical challenge due to oxidative stress and hepatocellular damage. This study evaluated the hepatoprotective potential of vanillic acid in mitigating drug-induced liver injury in rats. Hepatotoxicity was induced by administering isoniazid and rifampicin, followed by treatment with vanillic acid at two different doses (50 mg/kg and 100 mg/kg). Silymarin, a well-known hepatoprotective agent, was used as a reference standard. Biochemical markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), superoxide dismutase (SOD), catalase, and bilirubin, were assessed to evaluate liver function and oxidative stress.</div><div>Results revealed significant elevation in AST, ALT, ALP, and bilirubin levels and a reduction in antioxidant enzymes (SOD and catalase) in the isoniazid and rifampicin-treated group, indicating severe liver damage. Co-administration of vanillic acid significantly reduced these elevated markers and restored antioxidant enzyme levels in a dose-dependent manner. The higher dose of vanillic acid (100 mg/kg) exhibited a more pronounced hepatoprotective effect, comparable to silymarin. These findings suggest that vanillic acid exerts its protective effects by enhancing antioxidant defense, reducing oxidative stress, and preserving liver cell integrity.</div><div>This study highlights the therapeutic potential of vanillic acid in preventing drug-induced liver toxicity and underscores its role as a promising candidate for hepatoprotection during antitubercular therapy. Further investigation into its molecular mechanisms and clinical applicability is warranted.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the interplay of malarial pathogenesis, host immune response and oxidative stress: Implications for disease progression and therapeutic strategies","authors":"Muzi Nicolas Buthelezi ,&nbsp;Kgaugelo Josephine Masia ,&nbsp;Priscilla Masamba ,&nbsp;Mthokozisi Blessing Cedric Simelane ,&nbsp;Abidemi Paul Kappo","doi":"10.1016/j.amolm.2025.100082","DOIUrl":"10.1016/j.amolm.2025.100082","url":null,"abstract":"<div><div>Despite sustained efforts, malaria elimination in developing countries, particularly in Africa, remains a to be a public burden due to the evolution and emergence of resistance to most of the currently available antimalarials and insecticides. Over time, it has been argued that a thorough understanding of the parasite's biology and pathogenesis is important because it arises from a dynamic interplay between the host and the parasite. The lifecycle of the malarial parasite is complex, involving distinct developmental stages that each express specific antigens, which in turn trigger the immune system to either protect or promote pathophysiology. Malaria pathogenesis is thus a complex interplay of <em>Plasmodum</em>-induced red blood cell alterations and microvascular irregularities that lead to clinical symptoms and disease severity. Immune activation during malarial infection triggers a robust production of reactive oxygen and nitrogen species (ROS/RNS), contributing to oxidative stress, a characteristic seen during malarial infection and believed to exacerbate malarial pathophysiology. Therefore, this manuscript will examine the cellular mechanism underlying malarial pathophysiology, zoom in on oxidative stress, how it is linked to malarial severity and pathophysiology, and how it could be targeted to ameliorate ROS-mediated associated complications in malaria.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic potential of monocyte subsets, TNF-α, and IL-6 in pediatric celiac disease: A case-control study","authors":"Naglaa Makram Farag ,&nbsp;Noura Elbakry ,&nbsp;Mahmoud Mousa ,&nbsp;Mohamed S. Hemeda ,&nbsp;Zamzam Hassan Mohamed","doi":"10.1016/j.amolm.2025.100083","DOIUrl":"10.1016/j.amolm.2025.100083","url":null,"abstract":"<div><div>Celiac disease (CD) is a chronic autoimmune disorder of the small intestine, which is triggered by dietary gluten, especially in individuals with a genetic instinct. Monocytes play an important role in modifying intestinal immunity and inflammation, yet the importance of their subgroups in CD is not clear.</div></div><div><h3>Methods</h3><div>The case-control study was held at the Pediatric Outpatient Clinic of Minia University Hospital, including 57 CD patients and 29 age- and sex-matched healthy controls. Clinical examination, laboratory check, and history were demonstrated for all participants. The serum levels of the IL-6 and TNF-α cytokines were measured using ELISA, and most analysis was done using flow cytometry. The variable with significant differences was further evaluated for its clinical ability.</div></div><div><h3>Results</h3><div>Monocytes are more prevalent in CD patients than in controls. In the case group, the average level of monocyte CD14+/CD16+ and CD14–/CD16+ was much higher than in the control group of CD patients (P-value &lt;0.001). Additionally, CD patients who tested positive for antibodies had much higher levels of certain monocyte types compared to those who tested negative (p-values of 0.003, 0.011, and 0.001, respectively). Cytokines were not balanced, as levels of TNF-α and IL-6 were much higher in CD patients than in the control group. There was a significant positive relationship (p-value &lt;0.001) between different types of monocytes and the amounts of autoantibodies, TNF-α, and IL-6.</div></div><div><h3>Conclusion</h3><div>TNF-α, IL-6, and certain types of monocytes could be useful indicators for diagnosing CD, as we found important differences between the groups we studied.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-based insights into fatty acid modulation of lipid-sensing nuclear receptors PPARδ/γ for glycemic regulation","authors":"Shankar Gharge ,&nbsp;Charushila V. Balikai ,&nbsp;Sachin Gudasi","doi":"10.1016/j.amolm.2025.100079","DOIUrl":"10.1016/j.amolm.2025.100079","url":null,"abstract":"<div><div>This study explores the therapeutic potential of fatty acids (FA1-FA12) in the treatment of diabetes mellitus, focusing on their modulation of lipid-sensing nuclear receptors PPARδ/γ. Network pharmacology analysis highlighted key pathways involved in diabetes, including PI3K-Akt, MAPK, and insulin signaling, with targets such as PPAR, INSR, SLC2A4, and AKT1, suggesting a multi-target approach to disease modulation. To investigate their mechanism of action, a pharmacophore model was developed based on the PPAR-γ inhibitor Pioglitazone, offering insights into the essential structural features for ligand binding. Molecular docking studies revealed that FA1 and FA2 exhibited favorable binding affinities at the active sites of both PPAR-γ and PPAR-δ and MD trajectory analysis to evaluate binding orientation and stability of the molecules and the energy profiles of the molecules FA1 (Palmitic acid) and FA2 (Myristic acid), both in complex with the both PPAR-γ and PPAR-δ protein, were assessed. Additionally, computational analyses, including DFT and ADMET predictions, provided valuable information on the electronic and physicochemical properties of the fatty acids. Although these compounds displayed promising lipophilicity and permeability, their poor aqueous solubility indicates the need for optimization in drug development. Overall, this study lays a foundation for the exploration of fatty acids as potential therapeutic agents for diabetes, particularly through their modulation of PPARδ/γ activity for glycemic regulation.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods","authors":"Manisha Mandal ,&nbsp;Shyamapada Mandal","doi":"10.1016/j.amolm.2025.100080","DOIUrl":"10.1016/j.amolm.2025.100080","url":null,"abstract":"<div><div>SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the COVID-19 pandemic, is still a cause of global concern, and therefore, safe and effective treatment is desperately needed. Bacteriocins produced by probiotic microorganisms displayed therapeutic potentiality against infectious diseases, including COVID-19. NSP1 (non-structural protein-1) of SARS-CoV-2 acts as a host translation inhibitor and reduces host immune function, thereby increasing viral pathogenicity and virulence. This information encouraged us to evaluate the inhibitory role of plantaricin JK (Pln-JK) against SARS-CoV-2 NSP1 using <em>in silico</em> methods. Herein, we used PatchMAN and CABS-dock webtools to perform molecular docking between SARS-CoV-2 NSP1 and Pln-JK, which generated NSP1-Pln-JK models. We used a peptide antiviral, peptide 5 (PEP5) as a reference. The top models (based on the lowest binding score and cluster density) of both systems were subjected to predict the binding affinity (ΔG, kcal/mol) and dissociation constant (K_D, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and K_D value of 2.1 × 10⁻⁷. The binding affinity and K_D values for NSP1-PEP5 were −7.2 kcal/mol and 4.8 × 10⁻⁶ M (for PatchMan complex) and −5.9 kcal/mol and 4.8 × 10⁻⁵ M (for CABS-dock complex), respectively. HawkDock-based MM-GBSA binding free energies of CABS-dock and PatchMAN-generated complexes were −59.74 and −77.49 kcal/mol (for NSP1-Pln-JK) and −37.83 and −44.25 kcal/mol (for NSP1-PEP5), respectively. Further, molecular dynamic simulations-based MM-PBSA binding free energy confirmed NSP1-Pln-JK complex (−31.89 ± 0.91 kcal/mol) to be thermodynamically more stable than NSP1-PEP5 complex (−24.94 ± 0.6 kcal/mol). Pln-JK was predicted as non-allergic and non-toxic and thus emerged as a safe and effective molecule to combat SARS-CoV-2 infection. However, preclinical and clinical studies are needed before it can be considered as a prescription drug for the treatment of COVID-19.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational analysis of antibiotic resistance genes in Helicobacter pylori from Ghanaian dyspepsia patients: Implications for treatment strategies","authors":"Eric Gyamerah Ofori ,&nbsp;Foster Kyei ,&nbsp;Emmanuel Ayitey Tagoe ,&nbsp;Ansumana Sandy Bockarie ,&nbsp;Samuel Mawuli Adadey ,&nbsp;Osbourne Quaye ,&nbsp;Michael Buenor Adinortey ,&nbsp;Gordon Akanzuwine Awandare ,&nbsp;Cynthia Ayefoumi Adinortey","doi":"10.1016/j.amolm.2025.100078","DOIUrl":"10.1016/j.amolm.2025.100078","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic resistance jeopardizes the effectiveness of conventional treatment regimens for <em>Helicobacter pylori</em> infections, and this remains a major global health concern. <em>H. pylori</em> genes mutations negatively affect actions of most first line antibiotics. This study aimed to perform mutational analysis on <em>H. pylori</em> antibiotic resistance genes in Ghanaian patients diagnosed with dyspepsia.</div></div><div><h3>Materials and methods</h3><div>Antrum gastric biopsies were taken from 169 study participants, minced in Brain Heart Infusion broth and cultured. Sensitivity to antibiotics of <em>H. pylori</em> isolates was determined by disc diffusion. Extracted DNA were amplified and antibiotic resistance genes <em>gyrA</em>, <em>pbp1</em>, and <em>rdxA</em> sequenced. Resistance genes were analysed for base and point mutations using online databases and Ugene 45.0 software.</div></div><div><h3>Results</h3><div>Using rapid urease test, <em>H. pylori</em> infection prevalence was estimated to be 61%. Phenotypically, no sensitivity was recorded for metronidazole, amoxicillin, clarithromycin, and amoxicillin-clavulanic acid against the tested isolates. Resistance to levofloxacin was found to be 40% while 20% was recorded for each of tetracycline and ciprofloxacin. Mutations identified included G242 C/A, T254I, and S417T for <em>pbp1</em> gene in amoxicillin resistance; K2N, Q6H, Q50Stop, E75K, R90K, G98S, H99P, R131K, and A183V for <em>rdxA</em> gene; N87I/T, A97V, M191I, V199 M/A, H200Y, and G208E for <em>gyrA</em> gene in levofloxacin resistance.</div></div><div><h3>Conclusions</h3><div>There is high <em>H. pylori</em> antibiotic resistance in the region with amoxicillin, metronidazole, amoxicillin-clavulanic acid and clarithromycin showing no sensitivity to tested isolates. Tetracycline and ciprofloxacin may be more appropriate therapeutic regimen options against <em>H. pylori</em>. Observed resistance could be due to mutations in <em>rdxA</em>, <em>pbp1,</em> and <em>gyrA</em> genes.</div></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential antimicrobial properties of cytosine β-D-riboside derivatives through molecular dynamics and molecular docking exploration with bacterial and fungal proteins","authors":"Sarkar M.A. Kawsar ,&nbsp;Rahnuma Tabassum ,&nbsp;Nasrin Sultana Munia ,&nbsp;Suraj N. Mali ,&nbsp;Chin-Hung Lai ,&nbsp;Jannatul Ferdous ,&nbsp;Ferdausi Ali","doi":"10.1016/j.amolm.2025.100077","DOIUrl":"10.1016/j.amolm.2025.100077","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Nucleoside derivatives have contributed to the clinical and pharmaceutical fields as medicinal agents and approved drugs. The reaction of lauroyl chloride with cytosine β-D-riboside, i.e., cytidine (&lt;strong&gt;1&lt;/strong&gt;) in DMF/Et&lt;sub&gt;3&lt;/sub&gt;N, was the initiator step leading to 5′-&lt;em&gt;O&lt;/em&gt;-(lauroyl)cytidine (&lt;strong&gt;2&lt;/strong&gt;). Compound (&lt;strong&gt;2&lt;/strong&gt;) was reacted with various acylating agents and penetrated to give 2′,3′-di-&lt;em&gt;O&lt;/em&gt;-acyl derivatives (&lt;strong&gt;3&lt;/strong&gt;–&lt;strong&gt;6&lt;/strong&gt;). Physicochemical, spectroscopical, and elemental analysis methods were used to confirm the structure of the synthesized derivatives. &lt;em&gt;In vitro&lt;/em&gt; antimicrobial tests, coupled with PASS prediction, revealed that these derivatives are highly effective against distinct pathogenic bacteria. Compared with the standard nystatin, compound &lt;strong&gt;5&lt;/strong&gt; exhibited excellent antifungal efficacy against &lt;em&gt;Aspergillus flavus&lt;/em&gt; and &lt;em&gt;Aspergillus niger&lt;/em&gt;. Molecular docking analysis was performed to evaluate the binding interactions with the FimH lectin domain from &lt;em&gt;E. coli&lt;/em&gt; K12 and urate oxidase (Uox) from &lt;em&gt;Aspergillus flavus&lt;/em&gt;. For the FimH lectin domain, the binding affinities range from −2.35 to −9.32 kcal/mol (PyRx) and from −0.764 to 115.318 kcal/mol (iGEMDOCK), where compound &lt;strong&gt;2&lt;/strong&gt; exhibited the highest binding affinity and outperformed the standard azithromycin, forming hydrogen bonds with ASN A:138, GLN A:133, ASP A:54, ASN A:46, PHE A:1, and ASP A:47, along with Pi-alkyl interactions with TYR A:48. Similarly, compound &lt;strong&gt;5&lt;/strong&gt;, among the other synthesized compounds, strongly bound to Uox, with docking scores of −8.65 kcal/mol (PyRx) and −119.145 kcal/mol (iGEMDOCK), interacting with key residues such as THR A:173, LEU A:170, PHE A:258, and HIS A:256 through van der Waals forces, Pi‒Pi hydrophobic interactions, and hydrogen bonding. The RMSD, RMSF, and Rg analyses revealed that the docked complexes 4XO8:&lt;strong&gt;2&lt;/strong&gt; and 1R4U:&lt;strong&gt;5&lt;/strong&gt; exhibited stable protein‒ligand interactions, with no significant structural deviations observed during the 100 ns MD simulations. The hydrogen bonding and SASA results further support the stability of these complexes. According to DFT and FMO studies, compound &lt;strong&gt;5&lt;/strong&gt; should exhibit the highest chemical reactivity because it has the smallest Egap (4.84 eV). In silico, ADMET and toxicity studies were used to evaluate the pharmacokinetic characteristics, drug-likeness, and toxicity parameters of the newly synthesized compounds. Finally, SAR study was performed to predict any subsequent changes in the antimicrobial activities of these compounds modified at various positions in their structure, especially those modified with [CH&lt;sub&gt;3&lt;/sub&gt;(CH&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;10&lt;/sub&gt;CO] and {CH&lt;sub&gt;3&lt;/sub&gt;(CH&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;14&lt;/sub&gt;CO}] groups. These results suggest that derivatives of lauroyl cytidine have great promise as antimicrobial agents for treat","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}