{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:44Z","timestamp":1787028524263,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["RF----193021X0001"],"award-info":[{"award-number":["RF----193021X0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the past decades, the problem of bacterial resistance to most antibiotics has become a serious threat to patients\u2019 survival. Nevertheless, antibiotics of a novel class have not been approved since the 1980s. The development of antibiotic potentiators is an appealing alternative to the challenging process of searching for new antimicrobials. Production of H2S\u2014one of the leading defense mechanisms crucial for bacterial survival\u2014can be influenced by the inhibition of relevant enzymes: bacterial cystathionine \u03b3-lyase (bCSE), bacterial cystathionine \u03b2-synthase (bCBS), or 3-mercaptopyruvate sulfurtransferase (MST). The first one makes the main contribution to H2S generation. Herein, we present data on the synthesis, in silico analyses, and enzymatic and microbiological assays of novel bCSE inhibitors. Combined molecular docking and molecular dynamics analyses revealed a novel binding mode of these ligands to bCSE. Lead compound 2a manifested strong potentiating activity when applied in combination with some commonly used antibiotics against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The compound was found to have favorable in vitro absorption, distribution, metabolism, excretion, and toxicity parameters. The high effectiveness and safety of compound 2a makes it a promising candidate for enhancing the activity of antibiotics against high-priority pathogens.<\/jats:p>","DOI":"10.3390\/ijms242216331","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"16331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Naphthyl-Substituted Indole and Pyrrole Carboxylic Acids as Effective Antibiotic Potentiators\u2014Inhibitors of Bacterial Cystathionine \u03b3-Lyase"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4952-3561","authenticated-orcid":false,"given":"Andrey S.","family":"Kuzovlev","sequence":"first","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0379-3446","authenticated-orcid":false,"given":"Mikhail D.","family":"Zybalov","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Golovin","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 1\/73 Leninskie gori St., 119234 Moscow, Russia"},{"name":"Laboratory of Bioinformatics, Center of AI and Information Technologies, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-922X","authenticated-orcid":false,"given":"Maxim A.","family":"Gureev","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, Center of AI and Information Technologies, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"},{"name":"Laboratory of Bio- and Chemoinformatics, Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University, 8\/2 Trubetskaya, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariia A.","family":"Kasatkina","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Biryukov","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"},{"name":"Faculty of Biology, Lomonosov Moscow State University, 1\/12 Leninskie gori St., 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albina R.","family":"Belik","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey A.","family":"Silonov","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"},{"name":"Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-8934","authenticated-orcid":false,"given":"Maxim A.","family":"Yunin","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nailya A.","family":"Zigangirova","sequence":"additional","affiliation":[{"name":"Medical Microbiology Department, Laboratory of Chlamydiosis, National Research Center for Epidemiology and Microbiology Named after N. F. Gamaleya, 18 Gamaleya St., 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-0804","authenticated-orcid":false,"given":"Vasiliy V.","family":"Reshetnikov","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"},{"name":"Institute of Cytology and Genetics, Siberian Branch of RAS, 10 Akademika Lavrentyeva, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia E.","family":"Isakova","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri B.","family":"Porozov","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, Center of AI and Information Technologies, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"},{"name":"Laboratory of Bio- and Chemoinformatics, Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University, 8\/2 Trubetskaya, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-4183","authenticated-orcid":false,"given":"Roman A.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Sirius University of Science and Technology, Olympic Ave. 1, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Kraker, M.E.A., Stewardson, A.J., and Harbarth, S. (2016). Will 10 Million People Die a Year Due to Antimicrobial Resistance by 2050?. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002184"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/jac\/dkv484","article-title":"Antibiotics: From Prehistory to the Present Day","volume":"71","author":"Gould","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_3","unstructured":"(2023, October 14). WHO List of Bacteria for Which New Antibiotics Are Urgently Needed. Available online: https:\/\/www.who.int\/en\/news-room\/detail\/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ja.2010.62","article-title":"Antibiotic Discovery in the Twenty-First Century: Current Trends and Future Perspectives","volume":"63","author":"Donadio","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6420","DOI":"10.1016\/j.bmc.2016.08.035","article-title":"The Solithromycin Journey\u2014It Is All in the Chemistry","volume":"24","author":"Fernandes","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41579-019-0293-3","article-title":"Antibiotic Development\u2014Economic, Regulatory and Societal Challenges","volume":"18","author":"Balasegaram","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Capelo-Mart\u00ednez, J., and Igrejas, G. (2019). Antibiotic Drug Resistance, Wiley.","DOI":"10.1002\/9781119282549"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.1021\/acs.jmedchem.8b01781","article-title":"Antibiotic Adjuvants: Make Antibiotics Great Again!","volume":"62","author":"Douafer","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.tim.2016.06.009","article-title":"Antibiotic Adjuvants: Rescuing Antibiotics from Resistance","volume":"24","author":"Wright","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Fasnacht, M., and Polacek, N. (2021). Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.671037"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6022","DOI":"10.1073\/pnas.1703576114","article-title":"Mechanism of H2S-Mediated Protection against Oxidative Stress in Escherichia Coli","volume":"114","author":"Mironov","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1126\/science.1209855","article-title":"H2S: A Universal Defense Against Antibiotics in Bacteria","volume":"334","author":"Shatalin","year":"2011","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1126\/science.abd8377","article-title":"Inhibitors of Bacterial H2S Biogenesis Targeting Antibiotic Resistance and Tolerance","volume":"372","author":"Shatalin","year":"2021","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Borisov, V.B., and Forte, E. (2021). Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312688"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1111\/bph.12171","article-title":"Selectivity of Commonly Used Pharmacological Inhibitors for Cystathionine \u03b2-Synthase (CBS) and Cystathionine \u03b3-Lyase (CSE)","volume":"169","author":"Asimakopoulou","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kudli\u010dkov\u00e1, Z., Michalkov\u00e1, R., Salayov\u00e1, A., Ksia\u017eek, M., Vilkov\u00e1, M., Beke\u0161ov\u00e1, S., and Moj\u017ei\u0161, J. (2023). Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity. Molecules, 28.","DOI":"10.20944\/preprints202309.0098.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1039\/D3OB00381G","article-title":"Synthesis of SARS-CoV-2 M pro Inhibitors Bearing a Cinnamic Ester Warhead with in Vitro Activity against Human Coronaviruses","volume":"21","author":"Citarella","year":"2023","journal-title":"Org. Biomol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"134013","DOI":"10.1016\/j.molstruc.2022.134013","article-title":"Novel Series of N-Acyl Substituted Indole Based Piperazine, Thiazole and Tetrazoles as Potential Antibacterial, Antifungal, Antioxidant and Cytotoxic Agents, and Their Docking Investigation as Potential Mcl-1 Inhibitors","volume":"1271","author":"Jagadeesan","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1002\/chem.201303757","article-title":"Fluorescent Probes Based on Nucleophilic Substitution-Cyclization for Hydrogen Sulfide Detection and Bioimaging","volume":"20","author":"Peng","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dwyer, D.J., Kohanski, M.A., Hayete, B., and Collins, J.J. (2007). Gyrase Inhibitors Induce an Oxidative Damage Cellular Death Pathway in Escherichia Coli. Mol. Syst. Biol., 3.","DOI":"10.1038\/msb4100135"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.cell.2007.06.049","article-title":"A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics","volume":"130","author":"Kohanski","year":"2007","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112245","DOI":"10.1016\/j.ejmech.2020.112245","article-title":"Indole-Based Derivatives as Potential Antibacterial Activity against Methicillin-Resistance Staphylococcus Aureus (MRSA)","volume":"194","author":"Qin","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W597","DOI":"10.1093\/nar\/gkt376","article-title":"Analysis Tool Web Services from the EMBL-EBI","volume":"41","author":"McWilliam","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12675","DOI":"10.1074\/jbc.274.18.12675","article-title":"Kinetics and Inhibition of Recombinant Human Cystathionine \u03b3-Lyase","volume":"274","author":"Steegborn","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/17460441003605098","article-title":"Lipophilicity in Drug Discovery","volume":"5","author":"Waring","year":"2010","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2478\/acph-2019-0024","article-title":"Metabolic Stability and Its Role in the Discovery of New Chemical Entities","volume":"69","author":"Koczurkiewicz","year":"2019","journal-title":"Acta Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1124\/dmd.119.087163","article-title":"Plasma Protein Binding as an Optimizable Parameter for Acidic Drugs","volume":"47","author":"Gardiner","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/nrd3287","article-title":"The Effect of Plasma Protein Binding on in Vivo Efficacy: Misconceptions in Drug Discovery","volume":"9","author":"Smith","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1515\/BC.2003.043","article-title":"Determinants of Enzymatic Specificity in the Cys-Met-Metabolism PLP-Dependent Enzyme Family: Crystal Structure of Cystathionine \u03b3-Lyase from Yeast and Intrafamiliar Structure Comparison","volume":"384","author":"Messerschmidt","year":"2003","journal-title":"Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1016\/S0021-9258(18)99743-7","article-title":"Cystathionine \u03b3-Synthetase of Salmonella","volume":"241","author":"Kaplan","year":"1966","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1073\/pnas.1303186110","article-title":"Funnel Metadynamics as Accurate Binding Free-Energy Method","volume":"110","author":"Limongelli","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1038\/s41596-020-0342-4","article-title":"Ligand Binding Free-Energy Calculations with Funnel Metadynamics","volume":"15","author":"Raniolo","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"The PLUMED consortium (2019). Promoting Transparency and Reproducibility in Enhanced Molecular Simulations. Nat. Methods, 16, 670\u2013673.","DOI":"10.1038\/s41592-019-0506-8"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/jo971176v","article-title":"NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities","volume":"62","author":"Gottlieb","year":"1997","journal-title":"J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.biochi.2021.09.014","article-title":"Biological Evaluation and Spectral Characterization of a Novel Tetracenomycin X Congener","volume":"192","author":"Alferova","year":"2022","journal-title":"Biochimie"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/s41589-020-0578-x","article-title":"Tetracenomycin X Inhibits Translation by Binding within the Ribosomal Exit Tunnel","volume":"16","author":"Osterman","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_40","unstructured":"Qui, Y., Chen, Y., Zhang, G., Yu, L., and Mantri, R. (2017). Developing Solid Oral Dosage Forms, Elsevier."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/jps.21010","article-title":"Variability in Caco-2 and MDCK Cell-Based Intestinal Permeability Assays","volume":"97","author":"Volpe","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1046\/j.1432-1327.2000.01606.x","article-title":"Investigation of the Alamar Blue (Resazurin) Fluorescent Dye for the Assessment of Mammalian Cell Cytotoxicity","volume":"267","author":"Wilson","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1107\/S0021889883010985","article-title":"Analytical Molecular Surface Calculation","volume":"16","author":"Connolly","year":"1983","journal-title":"J. Appl. Crystallogr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1021\/ct200133y","article-title":"Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of pKa Values","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical Sampling through Velocity Rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"114107","DOI":"10.1063\/5.0020514","article-title":"Pressure Control Using Stochastic Cell Rescaling","volume":"153","author":"Bernetti","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10822-016-9948-6","article-title":"Resolving the Problem of Trapped Water in Binding Cavities: Prediction of Host\u2013Guest Binding Free Energies in the SAMPL5 Challenge by Funnel Metadynamics","volume":"31","author":"Bhakat","year":"2017","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: A Software Program for pKa Prediction and Protonation State Generation for Drug-like Molecules","volume":"21","author":"Shelley","year":"2007","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Repasky, M.P., Shelley, M., and Friesner, R.A. (2007). Flexible Ligand Docking with Glide. Curr. Protoc. Bioinform., 18.","DOI":"10.1002\/0471250953.bi0812s18"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Suenaga, A., Okimoto, N., Hirano, Y., and Fukui, K. (2012). An Efficient Computational Method for Calculating Ligand Binding Affinities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042846"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1002\/prot.23106","article-title":"The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling","volume":"79","author":"Li","year":"2011","journal-title":"Proteins"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ejmech.2012.01.014","article-title":"Hybrids of Privileged Structures Benzothiazoles and Pyrrolo[2,1-c] [1,4]Benzodiazepin-5-One, and Diversity-Oriented Synthesis of Benzothiazoles","volume":"50","author":"Idrees","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","first-page":"2152","article-title":"From N\u2013H Nitration to Controllable Aromatic Mononitration and Dinitration\u2500The Discovery of a Versatile and Powerful N-Nitropyrazole Nitrating Reagent","volume":"2","author":"Yang","year":"2022","journal-title":"JACS"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/jm00091a010","article-title":"1,3,6-Trisubstituted Indoles as Peptidoleukotriene Antagonists: Benefits of a Second, Polar, Pyrrole Substituent","volume":"35","author":"Brown","year":"1992","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12329","DOI":"10.1021\/jacs.9b05092","article-title":"Light-Stabilized Dynamic Materials","volume":"141","author":"Houck","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6288","DOI":"10.1021\/acs.orglett.1c02084","article-title":"Synthesis of Isotopically Labeled, Spin-Isolated Tyrosine and Phenylalanine for Protein NMR Applications","volume":"23","author":"Young","year":"2021","journal-title":"Org. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111986","DOI":"10.1016\/j.ejmech.2019.111986","article-title":"Antiproliferative Activity of Diarylnaphthylpyrrolidine Derivative via Dual Target Inhibition","volume":"188","author":"Verma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e202209895","DOI":"10.1002\/anie.202209895","article-title":"Synthesis of Atropisomeric Hydrazides by One-Pot Sequential Enantio- and Diastereoselective Catalysis","volume":"61","author":"Portolani","year":"2022","journal-title":"Angew. Chem. Int. Ed."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16331\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:12Z","timestamp":1760131392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":60,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216331"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216331","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}