Molecular Diversity最新文献

{"title":"Immunoinformatics investigation on pathogenic Escherichia coli proteome to develop an epitope-based peptide vaccine candidate.","authors":"Soham Chowdhury, Pinkan Sadhukhan, Nibedita Mahata","doi":"10.1007/s11030-024-11034-0","DOIUrl":"https://doi.org/10.1007/s11030-024-11034-0","url":null,"abstract":"<p><p>Escherichia coli (E. coli), a gram-negative bacterium, quickly colonizes in the human gastrointestinal tract after birth and typically sustains a long-term, symbiotic relationship with the host. However, certain virulent strains of E. coli can cause diseases such as urinary tract infections, meningitis, and enteric disorders. The rising antibiotic resistance among these strains has heightened the urgency for an effective vaccine. This study employs immunoinformatics and a reverse vaccinology technique to identify prospective antigens and create an efficient vaccine construct. In this study, we reported the \"Attaching and Effacing Protein\" a novel outer-membrane protein conserved in all pathogenic E. coli strains, based on proteome screening. We developed an in silico multi-epitope vaccine that includes helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), B cell lymphocyte (BCL), and pan HLA DR-binding reactive epitope (PADRE) sequences, along with appropriate linkers and adjuvants. Machine Learning algorithms were used to evaluate antigenicity, solubility, stability, and non-allergenicity of the vaccine construct. Additionally, molecular docking analysis revealed that vaccine construct has a strong predicted binding affinity for human toll-like receptors on the cell surface. In this context, laboratory validations are necessary to demonstrate the effectiveness of the possible vaccine design that showed encouraging findings through computational validation.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"You must be flexible enough to be trained, Mr. Dynamics simulator.","authors":"Ammar Usman Danazumi, Haruna Isiyaku Umar","doi":"10.1007/s11030-023-10689-5","DOIUrl":"10.1007/s11030-023-10689-5","url":null,"abstract":"<p><p>This article highlights two major problems associated with molecular dynamics studies: poor parameterization of systems and misleading interpretation of data. To address these issues, we advocate for meticulous system parameterization and careful interpretation of statistics within the framework of the study system, with a focus on high-quality and rigorous simulations. Our letter aims to encourage the adoption of the best practices in the field.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"2731-2733"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration","authors":"Ahmed M. El-Saghier,&nbsp;Souhaila S. Enaili,&nbsp;Aly Abdou,&nbsp;Asmaa M. Kadry","doi":"10.1007/s11030-023-10761-0","DOIUrl":"10.1007/s11030-023-10761-0","url":null,"abstract":"<div><h3>Introduction</h3><p>The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed.</p><h3>Problem statement</h3><p>The SARS-CoV-2 main protease (M^pro) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of M^pro enzyme can be an effective strategy for developing new COVID-19 drugs.</p><h3>Methodology</h3><p>An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-<i>N</i>-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski’s rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (M^pro) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis.</p><h3>Findings</h3><p>The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from − 7.33 kcal/mol (compound <b>6</b>) and − 7.22kcal/mol (compound <b>5</b>) to − 6.54 kcal/mol (compounds <b>8</b> and <b>9</b>). The top-ranked compounds (<b>5</b> and <b>6</b>) had lower HOMO–LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level.</p><h3>Recommendation</h3><p>These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 1","pages":"249 - 270"},"PeriodicalIF":3.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green preparation of new pyrimidine triazole derivatives via one-pot multicomponent reactions of guanidine","authors":"Nasrin Karami Hezarcheshmeh,&nbsp;Farideh Godarzbod,&nbsp;Media Noori Abdullah,&nbsp;Zinatossadat Hossaini","doi":"10.1007/s11030-023-10754-z","DOIUrl":"10.1007/s11030-023-10754-z","url":null,"abstract":"<div><p>In this research the goal was to produce novel pyrimidine triazole compounds in high yields using triethylamin as an efficient catalyst. These new compounds were synthesized by using multicomponent reaction of aldehydes, guanidine, electron deficient acetylenic compounds, <i>tert</i>-butyl isocyanide and hydrazonoyle chloride in aqueous media. Due to the presence of an NH group, which was assessed using two different methodologies, newly synthesized pyrimidine triazoles have antioxidant properties. Additionally, the antibacterial activity of newly created pyrimidine triazoles was assessed using the disk distribution method with two different types of Gram-positive bacteria and Gram-negative bacteria, demonstrating that the use of these compounds prevented the growth of bacteria. Applied to the preparation of pyrimidine triazole derivatives, this method has short reaction times, high product yields, and the ability to separate catalyst and product using simple procedures.</p></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 1","pages":"217 - 228"},"PeriodicalIF":3.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An efficient one-pot synthesis and docking studies of bioactive new antiproliferative dispiro[oxindole/acenaphthylenone‒benzofuranone] pyrrolidine scaffolds.","authors":"Tushar R Sutariya, Gaurangkumar C Brahmbhatt, Hiralben D Atara, Narsidas J Parmar, RajniKant, Vivek K Gupta, Irene Lagunes, José M Padrón, Prashant R Murumkar, Mayank Kumar Sharma, Mange Ram Yadav","doi":"10.1007/s11030-023-10741-4","DOIUrl":"https://doi.org/10.1007/s11030-023-10741-4","url":null,"abstract":"<p><p>A new and efficient method has been developed to synthesize dispiro[oxindole/acenaphthylenone-benzofuranone]pyrrolidine compounds. This is done by triggering the 1,3-dipolar cycloaddition reaction of azomethine ylides by reacting isatin/acenaphthoquinone with L-picolinic acid/L-proline/sarcosine/L-thioproline/tetrahydroisoquinolines, in a highly regioselective manner in an ionic liquid [DBU][Ac] with 4'-chloro-auron[2-(4-chlorobenzylidene)benzofuran-3(2H)-one]. Single-crystal X-ray diffraction data support the proposed structures of the new compounds. The heterocycles derived from amino acids such as L-picolinic acid, L-proline, and L-thioproline showed significant inhibitory effects against six human solid tumors, including lung, breast, cervix, colon, and others. These new structures were also tested in the active sites of the MDM2 receptor to further study their antiproliferative effects.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New tetrazolopyrrolidine-1,2,3-triazole analogues as potent anticancer agents: design, synthesis and molecular docking studies.","authors":"Siva Kumar Gandham, Amit A Kudale, Tejeswara Rao Allaka, Kalyani Chepuri, Anjali Jha","doi":"10.1007/s11030-023-10762-z","DOIUrl":"https://doi.org/10.1007/s11030-023-10762-z","url":null,"abstract":"<p><p>1,2,3-Triazole and tetrazole derivatives bearing pyrrolidines are found to exhibit notable biological activity and have become useful scaffolds in medicinal chemistry for application in lead discovery and optimization. We report design, synthesis and molecular docking studies of tetrazolyl-1,2,3-triazole derivatives (7a-i) bearing pyrrolidine moiety and evaluating their anticancer activity against four cancer cell lines viz. Hela, MCF-7, HCT-116 and HepG2. The structures of the new compounds were ascertained by spectral means IR, NMR: ¹H &¹³C and Mass spectrum. From the studies compounds7a and 7i exhibited significant anticancer activity against the Hela cell line with IC₅₀ = 0.32 ± 1.00, 1.80 ± 0.22 μM when compared to reference drug Doxorubicin (IC₅₀ = 2.34 ± 0.11 μM), whereas 7h, 7i, and 7b were found to be active against MCF-7, HCT-116 and HepG2 cell lines with IC₅₀ = 3.20 ± 1.40, 1.38 ± 0.06 and 0.97 ± 0.12 μM respectively. Notably 7a exhibited highest conventional hydrogen bondings TyrA:40, SerA:17, LysA:117, AlaA:146, Tyr218 with 3HB4and SerA:17, LysA:117, AlaA:146, TyrA:40 with 6IBZ and docking energy - 10.85, - 8.21 kcal/mol respectively. These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME. The results of the in vitro and in silico studies suggest that the tetrazole incorporated pyrrolidine-triazoles may possess the ideal structural requirements for further developing new anticancer agents.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-silico scaffold- hopping approach to design novel inhibitors against gp130: A potential therapeutic application in cancer and Covid-19.","authors":"Alankar Roy, Ishani Paul, Shreya Luharuka, Sujay Ray","doi":"10.1007/s11030-023-10737-0","DOIUrl":"https://doi.org/10.1007/s11030-023-10737-0","url":null,"abstract":"<p><p>An upregulation of the gp130-signalling cascade has been reported in multiple cancers, making gp130 an attractive target for the development of anticancer drugs. An inverted-funnel-like approach was utilised along with various structure-based drug designing strategies to discover and optimise novel potential inhibitors of gp130. The study resulted in the discovery of 2 ligands- 435 and 510, both of which exhibit a very high-binding affinity towards the gp130 D1 domain which controls cytokine recognition and interaction thus being involved in complexation. The two resulting complexes remained stable over time with the ligands maintaining a steady interaction with the target. This inference is drawn from their RMSD, R_g, SASA and RMSF analysis. We also tested the protein folding patterns based on their principal component analysis, energy of surface and landscape. The leads also displayed a more favourable ADMET profile than their parent compounds. The two lead candidates show a better therapeutic profile in comparison to the two existing drugs- bazedoxifene and raloxifene. Both these potential leads can be addressed for their activity in-vitro and can be used as a potential anti-cancer treatment as well as to combat Covid-19 related cytokine storm.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, X-ray crystal structure, and antimicrobial evaluation of novel quinazolinone derivatives containing the 1,2,4-triazole Schiff base moiety and an isopropanol linker.","authors":"Lan Yang, Muhan Ding, Jun Shi, Na Luo, Yuli Wang, Dongyun Lin, Xiaoping Bao","doi":"10.1007/s11030-023-10749-w","DOIUrl":"https://doi.org/10.1007/s11030-023-10749-w","url":null,"abstract":"<p><p>A series of novel quinazolinone derivatives (E1-E31) containing the 1,2,4-triazole Schiff base moiety and an isopropanol linker were designed, synthesized and assessed as antimicrobial agents in agriculture. All the target compounds were fully characterized by ¹ H NMR, ¹³ C NMR, and high-resolution mass spectrometry (HRMS). Among them, the structure of compound E12 was further confirmed via single crystal X-ray diffraction method. The experimental results indicated that many compounds displayed good in vitro antibacterial efficacies against the tested phytopathogenic bacteria including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Ralstonia solanacearum (Rs). For example, compounds E3, E4, E10, E13, and E22 had EC₅₀ (half-maximal effective concentration) values of 55.4, 39.5, 49.5, 53.5, and 57.4 µg/mL against Xoo, respectively, superior to the commercialized bactericide Bismerthiazol (94.5 µg/mL). In addition, the antibacterial efficacies of compounds E10 and E13 against Xac were about two times more effective than control Bismerthiazol, in terms of their EC₅₀ values. Last, the antifungal assays showed that compounds E22 and E30 had the inhibition rates of 52.7% and 54.6% at 50 µg/mL against Gibberella zeae, respectively, higher than the commercialized fungicide Hymexazol (48.4%).</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of phytochemical compounds against Marburg virus using QSAR, molecular dynamics, and free energy landscape.","authors":"Ali A Rabaan,&nbsp;Muhammad A Halwani,&nbsp;Mohammed Garout,&nbsp;Jawaher Alotaibi,&nbsp;Bashayer M AlShehail,&nbsp;Nouf Alotaibi,&nbsp;Souad A Almuthree,&nbsp;Ahmad A Alshehri,&nbsp;Mohammed Abdulrahman Alshahrani,&nbsp;Basim Othman,&nbsp;Abdulaziz Alqahtani,&nbsp;Mohammed Alissa","doi":"10.1007/s11030-023-10753-0","DOIUrl":"https://doi.org/10.1007/s11030-023-10753-0","url":null,"abstract":"<p><p>Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔG_TOTAL = - 30.78 kcal/mol) and 74977521 (ΔG_TOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of efflux pump inhibitors for Pseudomonas aeruginosa MexAB-OprM via ligand-based pharmacophores, 2D-QSAR, molecular docking, and molecular dynamics approaches.","authors":"Thien-Vy Phan,&nbsp;Vu-Thuy-Vy Nguyen,&nbsp;Minh-Tri Le,&nbsp;Bao Gia Dang Nguyen,&nbsp;Thanh-Thao Vu,&nbsp;Khac-Minh Thai","doi":"10.1007/s11030-023-10758-9","DOIUrl":"https://doi.org/10.1007/s11030-023-10758-9","url":null,"abstract":"<p><p>Efflux pumps have been reported as one of the significant mechanisms by which bacteria evade the effects of multiple antibiotics. The tripartite efflux pump MexAB-OprM in Pseudomonas aeruginosa is one of the most significant multidrug efflux systems due to its broad resistance to antibiotics such as chloramphenicol, fluoroquinolones, lipophilic β-lactam antibiotics, nalidixic acid, novobiocin, rifampicin, and tetracycline. A promising strategy to overcome this resistance mechanism is to combine antibiotics with efflux pump inhibitors (EPIs), which can increase their intracellular concentration to enhance their biological activities. Based on 143 EPIs with chemically diverse skeletons, the 3D pharmacophore and 2D-QSAR modelings were developed and used for the virtual screening on 9.2 million compounds including ZINC15, DrugBank, and Traditional Chinese Medicine databases to identify new EPIs. The molecular docking was also performed to evaluate the binding affinity of potential EPIs to the distal-binding pocket of MexB and resulted in 611 potential EPIs. The structure-activity relationship analyses suggested that nitrogen heterocyclic compounds, piperazine and pyridine scaffolds, and amide derivatives are the most favorable chemically features for MexAB inhibitory activities. The results from molecular dynamics analysis in 100 ns indicated that ZINC009296881 and ZINC009200074 were the most potential MexB inhibitors with strong binding affinity to the distal pocket and MM/GBSA ∆G_bind values of - 38.97 and - 30.19 kcal mol^-1, respectively. The predicted pharmacokinetic properties and toxicity of these compounds indicated their potential oral drugs. Multistep virtual screening of EPIs for MexAB-OprM, efflux pump multidrug resistant of P. aeruginosa.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}