Journal of Molecular Recognition最新文献

{"title":"Comprehensive analysis on the diagnostic role of circulatory exosome-based miR-92a-3p for osteoblastic metastases in prostate adenocarcinoma","authors":"Gayathri Ashok,&nbsp;Rohini Das,&nbsp;Anand Anbarasu,&nbsp;Sudha Ramaiah","doi":"10.1002/jmr.3042","DOIUrl":"10.1002/jmr.3042","url":null,"abstract":"<p>Prostate adenocarcinoma (PRAD) is the second leading cause of death in men and the key factor that attributes to the severity and higher mortality rates is the tumor's ability to promote osteoblastic metastases (OM). Currently, no blood-based biomarkers are present that bridges the crosstalk between PRAD and OM progression. Conversely, circulatory microRNAs (miRNAs) are gaining interest among the scientific community for its potential as blood-based markers for cancer detection. Using computational pipeline, this study screened exosome-based miRNA that is functionally regulating OM in PRAD. We retrieved the expression profile of miRNA, mRNA from PRAD microarray, and RNA-Seq samples deposited in global repositories and identified the differentially expressed miRNAs (DEMs) and differentially expressed genes. Thereafter, the average expression of the miRNAs was identified in extracellular vesicle specifically in exosomes. Survival analysis and clinical profiling identified functionally significant miR-92a-3p to be a key factor in OM. This was further examined by the interactions with various noncoding RNA elements, transcription factors, oncogenes, tumor suppressor genes, and protein kinases regulated by miR-92a-3p. Identifying the expression pattern, nodal metastasis, Gleason score, and hazard ratio deciphered the critical role of the targets regulated by miR-92a-3p. Further, binding association analyzed through energy, seed match and accessibility showed the miRNA-targets involved in cytokine, TGF-β, and Wnt signaling having close regulatory role in promoting OM. Our findings highlight the potent role of miR-92a-3p as blood-based diagnostic biomarker for OM. The comprehensive insights from our study can be elemental in designing diagnostic biomarker for PRAD.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9852576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies on the synthesis, spectroscopy, thermal properties, docking, and biology of new Schiff base and its mono- and binuclear complexes","authors":"Khlood Abou-Melha","doi":"10.1002/jmr.3026","DOIUrl":"10.1002/jmr.3026","url":null,"abstract":"<p>A novel Schiff base has been synthesized from the condensation of the 3-formyl-2-hydroxybenzoic acid and 4-nitrobenzene-1,2-diamine. The new ligand was found to have two coordination sites. So, it has the capability to form mono- and binuclear complexes with different metal ions. The free ligand and its mono- and binuclear cobalt(II) complexes have been characterized by UV–Visible spectra, IR, elemental analyzes, H¹ NMR, conductimetric, thermal, and magnetic measurements. Results indicated that the cobalt(II) ion is attached to the inside coordination site and the second metal ion attached to the outside coordination site. The complexes are all non-electrolytes, as demonstrated by the molar conductance tests. The thermodynamic parameters of the metal complexes are calculated using Horowitz Metzger and Coats-Redfern methods. The complexes' bonding properties have also been estimated. Molecular docking was employed to forecast the interaction of the prepared with the Candida-albicans receptor (1zap). The biological activities of these metal complexes were tested against some bacteria and fungi. It is evident from the biological screening data that the prepared Co(II) binuclear complexes exhibit predominant activity against <i>Candida albicans</i>, <i>Penicillium oxalicum</i> and <i>Escherichia coli</i>, while they have no activity against <i>Micrococcus roseus</i> and <i>Micrococcus luteus</i>.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isothermal titration calorimetry binding properties of Cibacron Blue F3GA in complex with human serum albumin","authors":"Cenk A. Andac,&nbsp;Sena Çağlar,&nbsp;Adil Denizli,&nbsp;Müge Andaç","doi":"10.1002/jmr.3040","DOIUrl":"10.1002/jmr.3040","url":null,"abstract":"<p>Binding interactions between Cibacron Blue-F3GA (CB-F3GA) and human serum albumin (HSA, at physiologically ten-fold lower concentration) was studied by isothermal titration calorimetry (ITC) and <i>in-silico</i> docking computations. ITC experiments revealed two separate binding sites on HSA with different binding affinities for CB-F3GA. The high-affinity binding site (PBS-II) on HSA binds CB-F3GA at nanomolar scale (K_D1 = 118 ± 107 nM) with favorable binding enthalpy (ΔH^o₁ = − 6.47 ± 0.44 kcal/mol) and entropy (−TΔS^o₁ = −2.98 kcal/mol) energies. CB-F3GA binds to the low-affinity binding site (PBS-I) at μM scale (K_D2 = 31.20 ± 18.40 μM) with favorable binding enthalpy (ΔH^o₁ = − 5.03 ± 3.86 × 10⁻² kcal/mol) and entropy (−TΔS^o₁ = −1.12 kcal/mol) energies. ITC binding data strongly suggest that CB-F3GA binding to PBS-II site increases the formation of dimeric-HSA clusters (N₁ = 2.43 ± 0.50), while binding to PBS-I leads to tetrameric-HSA clusters (N₂ = 4.61 ± 0.90). These results suggest that a higher degree of HSA aggregation upon drug binding may be expected under physiological conditions, a notion that should be further investigated for the delivery and toxicity of drug−HSA interactions.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic aspects of binding of telomeric over parallel G-quadruplex with novel synthesized Knoevenagel condensate 4-nitrobenzylidene curcumin","authors":"Padma Sharma,&nbsp;Niki Sweta Jha","doi":"10.1002/jmr.3041","DOIUrl":"10.1002/jmr.3041","url":null,"abstract":"<p>The introduction of small ligands to stabilise G-quadruplex DNA structures is a promising method for developing anti-cancer drugs. It is challenging to stabilise the G-quadruplex structure, which can take on a variety of topologies and is known to inhibit specific biological processes. To achieve this, 4-nitrobenzylidene curcumin (NBC), the Knoevenagel condensate of curcumin, was synthesized and characterized. The interaction of 4-nitrobenzylidene curcumin with parallel (c-MYC) and hybrid (H-telo) G-quadruplex structures was studied by circular dichroism (CD) spectroscopy, UV-thermal melting, differential scanning calorimetry (DSC), absorption spectroscopy, fluorescence spectroscopy and docking studies. The outcome demonstrates that, in a K⁺-rich solution, the ligand NBC can stabilise the parallel c-MYC and hybrid H-telo G-quadruplex structures by 5°C. The absorption and fluorescence studies show that the ligand NBC binds to c-MYC and H-telo with affinities of 0.3 × 10⁶ M⁻¹ and 0.6 × 10⁶ M⁻¹, respectively. The ligand interacts with the terminal G-quartet of the quadruplex structure via intercalation and the groove mode of binding, well supported by docking studies as well. NBC has more potent antioxidant activity as compared to the curcumin and 4-nitro benzaldehyde. It was also found to have higher cytotoxic activity towards cell line such as HeLa and MCF-7, while less cytotoxic for healthy Vero cells. Overall, the results show that the Knoevenagel product of curcumin can work better as a G-quadruplex binder and could be used as a possible treatment.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10218524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of new compounds bearing methyl sulfonyl pharmacophore as selective COX-2 inhibitor","authors":"Taha Almarsoomi,&nbsp;Derya Osmaniye,&nbsp;Begüm Nurpelin Sağlık,&nbsp;Serkan Levent,&nbsp;Usman Ghani,&nbsp;Yusuf Özkay,&nbsp;Zafer Asım Kaplancıklı","doi":"10.1002/jmr.3025","DOIUrl":"10.1002/jmr.3025","url":null,"abstract":"<p>Cyclooxygenase, also known as prostaglandin H2 synthase (PGH2), is one of the most important enzymes in pharmacology because inhibition of COX is the mechanism of action of most nonsteroidal anti-inflammatory drugs. In this study, ten thiazole derivative compounds had synthesized. The analysis of the obtained compounds was performed by ¹H NMR and ¹³C NMR methods. By this method, the obtained compounds could be elucidated. The inhibitory effect of the obtained compounds on cyclooxygenase (COX) enzymes was investigated. The encoded compounds <b>5a</b>, <b>5b</b>, and <b>5c</b> were found to be the most potent compared to the reference compounds ibuprofen (IC₅₀ = 5.589 ± 0.278 μM), celecoxib (IC₅₀ = 0.132 ± 0.004 μM), and nimesulide (IC₅₀ = 1.692 ± 0.077 μM)against COX-2 isoenzyme. The inhibitory activity of <b>5a</b>, <b>5b</b>, and <b>5c</b> is approximate, but the <b>5a</b> derivative proved to be the most active in the series with an IC₅₀ value of 0.180 ± 0.002 μM. The most potent COXs inhibitor was <b>5a</b>, which was further investigated for its potential binding mode by a molecular docking study. Compound <b>5a</b> was found to be localized at the active site of the enzyme, like celecoxib, which has a remarkable effect on COXs enzymes.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quorum sensing-associated bacterial phenazines are potential ligands of human α1-acid glycoprotein","authors":"Ferenc Zsila","doi":"10.1002/jmr.3027","DOIUrl":"https://doi.org/10.1002/jmr.3027","url":null,"abstract":"<p>α₁-Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen <i>Pseudomonas aeruginosa</i> and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π–π and CH–π interactions. The estimated affinity constants (~10⁵ M⁻¹) predict that these secondary metabolites could be trapped inside the β-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50134042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction","authors":"Ting Hu,&nbsp;Qianghong Zhao,&nbsp;Ming Wang,&nbsp;Kai Zhou,&nbsp;Zhining Xia,&nbsp;Yike Huang","doi":"10.1002/jmr.3024","DOIUrl":"10.1002/jmr.3024","url":null,"abstract":"<p>Based on the synergistic action of hydrogen bond and electrostatic interaction, provided by methacrylic acid and 2-aminoethyl ester hydrochloride (FM2), respectively, novel molecularly imprinted polymers (SA-MIPs) were designed to improve its selective recognition ability. Diclofenac sodium (DFC) was chosen as the template molecule of this study. The interaction and their recognition sites between two functional monomers and templates were confirmed by nuclear magnetic resonance hydrogen spectroscopy. Because of the synergistic action of hydrogen bond and electrostatic interaction, the imprinting factor (IF) of SA-MIPs (IF = 2.26) is superior to the corresponding monofunctional monomer imprinting materials (IF = 1.52, 1.20) and the materials using two functional monomers with an only single type of interaction (IF = 1.54, 1.75). The results of selective adsorption experiments indicate that the selective recognition ability of SA-MIPs is significantly better than that of the other four MIPs, and the difference in selectivity coefficient for methyl orange is the largest between SA-MIPs and the MIPs only using FM2, which is about 70 times. In addition, x-ray photoelectron spectroscopy was used to verify the interaction between SA-MIPs and the template. This work and its explanation of the interaction mechanism at the molecular level will be helpful for the rational design of novel MIPs with higher selectivity. Besides, SA-MIPs have good adsorption performance (37.75 mg/g) for DFC in aqueous solutions, which could be used as potential adsorption materials for the effective removal of DFC in the aquatic environment.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and development of novel potential inhibitors of the human USP21 enzyme using a pharmacophore-based virtual screening technique","authors":"Alankar Roy,&nbsp;Shreya Luharuka,&nbsp;Ishani Paul,&nbsp;Sujay Ray","doi":"10.1002/jmr.3023","DOIUrl":"10.1002/jmr.3023","url":null,"abstract":"<p>An overexpression and increase have been observed in the concentration and activity of the ubiquitin-specific protease 21 (USP21) enzyme in many cancers, necessitating the need for the development of new inhibitor drugs against the same. The current study attempts to discover one such novel potential inhibitor of USP21 by the application of various bioinformatics techniques which include molecular modeling, pharmacophore mapping, pharmacophore-based virtual screening, molecular docking, and ADMET prediction followed by molecular dynamics simulations. Following this inverted funnel-like approach, we finally ended up with one ligand–ZINC02422616 which displays a very high binding affinity toward the USP21 domain. This ligand contains all the pharmacophoric features displayed by the compounds that are potential inhibitors of the USP21 domain. Moreover, it shows a favorable pharmacokinetic, pharmacodynamic, and ADMET profile, along with strong hydrophobic interaction and hydrogen bonding with the domain. Simulation studies showed that the complex remains stable over time, with the bound protein displaying a more constrained motion in the conformational space compared to the unbound form. The ligand showed a highly favorable free energy landscape/surface, forming several energy minima's in contrast to the unbound domain in which most conformations occupied a relatively higher energy state. Moreover, the ligand also displayed a <i>K</i>_d of 422.8 nM and a free energy of binding Δ<i>G</i> of −8.6 kcal/mol, both of which indicate a very high affinity toward the target domain. This potential drug candidate can then be used as a viable treatment method for many types of cancers caused by USP21.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcones bearing nitrogen-containing heterocyclics as multi-targeted inhibitors: Design, synthesis, biological evaluation and molecular docking studies","authors":"Yusuf Sıcak,&nbsp;Hüseyin Kekeçmuhammed,&nbsp;Ayşegül Karaküçük-İyidoğan,&nbsp;Tuğba Taşkın-Tok,&nbsp;Emine Elçin Oruç-Emre,&nbsp;Mehmet Öztürk","doi":"10.1002/jmr.3020","DOIUrl":"10.1002/jmr.3020","url":null,"abstract":"<p>In this work, a series of chalcones (<b>1a–d</b>, <b>2a–d</b>, <b>3a–d</b>, <b>4a–d</b>, and <b>5a–d</b>) were designed and synthesized by Claisen–Schmidt condensation. Also, their chemical structures were elucidated using UV–Vis, FT IR, ¹H NMR, ¹³C NMR, MS spectral data, and elemental analyses. Subsequently, the anticholinesterase, tyrosinase, urease inhibitory activities and antioxidant activities of all chalcones were evaluated. The inhibitory potential of all chalcones in terms of IC₅₀ value was observed to range from 7.18 ± 0.43 to 29.62 ± 0.30 μM against BChE by comparing with Galantamine (IC₅₀ 46.06 ± 0.10 μM) as a reference drug. Also, compounds <b>2c</b>, <b>3c</b>, <b>4c</b>, <b>4b</b>, and <b>4d</b> exhibited high anticholinesterase activity against both AChE and BChE enzymes. The tyrosinase inhibitory activity results revealed that three compounds (IC₅₀ 1.75 ± 0.83 μM for <b>2b</b>, IC₅₀ 2.24 ± 0.11 μM for <b>3b</b>, and IC₅₀ 1.90 ± 0.64 μM for <b>4b</b>) displayed good inhibitory activity against tyrosinase compared with kojic acid (IC₅₀ 0.64 ± 0.12 μM). In addition, other different three chalcones (IC₅₀ 22.34 ± 0.25 μM for <b>2c</b>, IC₅₀ 20.98 ± 0.08 μM for <b>3c</b>, and IC₅₀ 18.26 ± 0.13 μM for <b>4c</b>) showed excellent inhibitory activity against the urease by comparing with thiourea (IC₅₀ 23.08 ± 0.19 μM). Compounds <b>3c</b> and <b>4c</b> showed the best potency in all antioxidant activity tests. In light of these findings, the structure–activity relationship for compounds was also described. Furthermore, molecular modeling studies, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacophore analyses of compounds, gave important information about the interactions and drug-likeness properties. As a result, all chalcones exhibited suitable ADMET findings, predicting good oral bioavailability.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repositioning to discover novel ornithine decarboxylase inhibitors against visceral leishmaniasis","authors":"Sabahat Yasmeen Sheikh,&nbsp;Waseem Ahmad Ansari,&nbsp;Firoj Hassan,&nbsp;Tabrez Faruqui,&nbsp;Mohammad Faheem Khan,&nbsp;Yusuf Akhter,&nbsp;Abdul Rahman Khan,&nbsp;Maqsood A. Siddiqui,&nbsp;Abdulaziz A. Al-Khedhairy,&nbsp;Malik Nasibullah","doi":"10.1002/jmr.3021","DOIUrl":"10.1002/jmr.3021","url":null,"abstract":"<p>Visceral leishmaniasis (VL) is caused by <i>Leishmania donovani</i> (<i>Ld</i>), and most cases occur in Brazil, East Africa, and India. The treatment for VL is limited and has many adverse effects. The development of safer and more efficacious drugs is urgently needed. Drug repurposing is one of the best processes to repurpose existing drugs. Ornithine decarboxylase (ODC) is an important target against <i>L. donovani</i> in the polyamine biosynthesis pathway. In this study, we have modeled the 3D structure of ODC and performed high-throughput virtual screening of 8630 ZINC database ligands against <i>Leishmania donovani</i> ornithine decarboxylase (<i>Ld</i> ODC), selecting 45 ligands based on their high binding score. It is further validated through molecular docking simulation and the selection of the top two lead molecules (ceftaroline fosamil and rimegepant) for Molecular Dynamics (MD) simulation, Density functional theory (DFT), and molecular mechanics generalized born surface area (MMGBSA) analysis. The results showed that the binding affinities of ceftaroline fosamil, and rimegepant are, respectively, −10.719 and 10.159 kcal/mol. The docking complexes of the two lead compounds, ceftaroline fosamil, and rimegepant, with the target ODC, were found stable during molecular dynamics simulations. Furthermore, the analysis of MMGBSA revealed that these compounds had a high binding free energy. The DFT analysis showed that the top lead molecules were more reactive than the standard drug (pentamidine). <i>In-silico</i> findings demonstrated that ceftaroline fosamil, and rimegepant might be recognized as potent antagonists against ODC for the treatment of VL.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}