{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:43:41Z","timestamp":1789127021813,"version":"build-2803163510"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sindh Higher Education Commission","award":["number SHEC\/SRSP\/MS-1\/7\/2020-21"],"award-info":[{"award-number":["number SHEC\/SRSP\/MS-1\/7\/2020-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16\u201324 \u00b5g\/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 \u00b5g\/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin\/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.<\/jats:p>","DOI":"10.3390\/molecules28010212","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T03:03:31Z","timestamp":1672110211000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0771-8184","authenticated-orcid":false,"given":"Farooq-Ahmad","family":"Khan","sequence":"first","affiliation":[{"name":"Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Yaqoob","sequence":"additional","affiliation":[{"name":"Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujaat","family":"Ali","sequence":"additional","affiliation":[{"name":"Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimra","family":"Tanveer","sequence":"additional","affiliation":[{"name":"Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-2754","authenticated-orcid":false,"given":"Sajda","family":"Ashraf","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-7923","authenticated-orcid":false,"given":"Khwaja Ali","family":"Hasan","sequence":"additional","affiliation":[{"name":"Molecular and Structural Biology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaden A. M.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyang","family":"Shou","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-8711","authenticated-orcid":false,"given":"Zaheer","family":"Ul-Haq","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-9249","authenticated-orcid":false,"given":"Zi-Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham R.","family":"El-Seedi","sequence":"additional","affiliation":[{"name":"International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China"},{"name":"Pharmacognosy Group, Department of Pharmaceutical Biosciences, BMC, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden"},{"name":"International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing (Jiangsu University), Jiangsu Education Department, Nanjing 210024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114145","DOI":"10.1016\/j.ejmech.2022.114145","article-title":"Identification of Thiophene-Benzenesulfonamide Derivatives for the Treatment of Multidrug-Resistant Tuberculosis","volume":"231","author":"Qin","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10706","DOI":"10.1002\/anie.201209979","article-title":"Combating Multidrug-Resistant Bacteria: Current Strategies for the Discovery of Novel Antibacterials","volume":"52","author":"Hodgkinson","year":"2013","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.bcp.2005.09.018","article-title":"Unmet Medical Needs in Antibacterial Therapy","volume":"71","author":"Rice","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1007\/s00044-012-0223-7","article-title":"Integrating GUSAR and QSAR Analyses for Antimalarial Activity of Synthetic Prodiginines against Multi Drug Resistant Strain","volume":"22","author":"Mahajan","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., and Marusza, W. (2022). Molecular Mechanisms of Drug Resistance and Epidemiology of Multidrug-Resistant Variants of Neisseria Gonorrhoeae. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810499"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.2147\/DDDT.S329547","article-title":"The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design","volume":"15","author":"Ling","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yaqoob, S., Nasim, N., Khanam, R., Wang, Y., Jabeen, A., Qureshi, U., Ul-Haq, Z., El-Seedi, H.R., Jiang, Z.-H., and Khan, F.-A. (2021). Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid. Molecules, 26.","DOI":"10.3390\/molecules26051272"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Popio\u0142ek, \u0141. (2021). Updated Information on Antimicrobial Activity of Hydrazide-Hydrazones. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179389"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tetasy.2016.12.001","article-title":"The Role of Hydrazide Compounds in Asymmetric Synthesis","volume":"28","year":"2017","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00044-016-1756-y","article-title":"Hydrazide-Hydrazones as Potential Antimicrobial Agents: Overview of the Literature since 2010","volume":"26","year":"2017","journal-title":"Med. Chem. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10718","DOI":"10.1016\/j.tet.2013.10.062","article-title":"Facile, Efficient and Diastereoselective Synthesis of \u03b1-Hydrazine Tetrazoles through a Novel One-Pot Four-Component Reaction","volume":"69","author":"Ramezanpour","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1039\/C5NJ00845J","article-title":"Efficient Synthesis of Lower Rim \u03b1-Hydrazino Tetrazolocalix[4]Arenes via an Ugi-Azide Multicomponent Reaction","volume":"39","author":"Alavijeh","year":"2015","journal-title":"New J. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s13738-016-0817-y","article-title":"Application of SBA-Pr-SO3H as a Nanoreactor in the One-Pot Synthesis of Spiroquinazolinones","volume":"13","author":"Badiei","year":"2016","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0223-5234(01)01259-4","article-title":"Synthesis and Pharmacological Study of Ethyl 1-Methyl-5-(Substituted 3,4-Dihydro-4-Oxoquinazolin-3-Yl)-1H-Pyrazole-4-Acetates","volume":"36","author":"Maggio","year":"2001","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.comptc.2015.03.013","article-title":"Stabilization of the Transition Structures of Organocatalytic Asymmetric Direct Aldol Reaction in Wet Solvent Free Condition by the Formation of Water Assisted Supramolecular Network: A DFT Study","volume":"1062","author":"Chakrabarty","year":"2015","journal-title":"Comput. Theor. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Murugaiyan, J., Anand Kumar, P., Rao, G.S., Iskandar, K., Hawser, S., Hays, J.P., Mohsen, Y., Adukkadukkam, S., Awuah, W.A., and Jose, R.A.M. (2022). Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020200"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ejmech.2017.04.002","article-title":"Isoniazid Derivatives and Their Anti-Tubercular Activity","volume":"133","author":"Hu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/med.21557","article-title":"Harnessing the Untapped Potential of Nucleotide-binding Oligomerization Domain Ligands for Cancer Immunotherapy","volume":"39","author":"Nabergoj","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Egorova, A., Salina, E.G., and Makarov, V. (2021). Targeting Non-Replicating Mycobacterium Tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413317"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1007\/s10600-011-9779-6","article-title":"Antituberculosis Activity of Glycosides from Stevia Rebaudiana and Hybrid Compounds of Steviolbioside and Pyridinecarboxylic Acid Hydrazides","volume":"46","author":"Sharipova","year":"2011","journal-title":"Chem. Nat. Compd."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1021\/jm101510d","article-title":"Design, Synthesis, and Biological Evaluation of New Cinnamic Derivatives as Antituberculosis Agents","volume":"54","author":"De","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1016\/j.bmcl.2012.02.091","article-title":"Synthesis of Highly Potent Novel Anti-Tubercular Isoniazid Analogues with Preliminary Pharmacokinetic Evaluation","volume":"22","author":"Ramani","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1007\/s13346-018-0500-1","article-title":"Phenolic Acid-Tethered Isoniazid for Abrogation of Drug-Induced Hepatotoxicity: Design, Synthesis, Kinetics and Pharmacological Evaluation","volume":"8","author":"Bhilare","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/2231-4040.126984","article-title":"Plumbagin Analogs-Synthesis, Characterization, and Antitubercular Activity","volume":"5","author":"Nayak","year":"2014","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6910","DOI":"10.1016\/j.bmc.2013.09.034","article-title":"Synthesis and Antimycobacterial Activity of Isoniazid Derivatives from Renewable Fatty Acids","volume":"21","author":"Rodrigues","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.ejmech.2010.01.028","article-title":"Thiosemicarbazones, Semicarbazones, Dithiocarbazates and Hydrazide\/Hydrazones: Anti\u2014Mycobacterium Tuberculosis Activity and Cytotoxicity","volume":"45","author":"Pavan","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.22452\/mjs.vol28no2.8","article-title":"Synthesis and Biological Evaluation of Some Novel Nicotinic Acid Derivatives","volume":"28","author":"Ramalakshmi","year":"2009","journal-title":"Malays. J. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1080\/00397911.2021.1986841","article-title":"Synthesis of Novel Benzimidazole Containing Antimicrobial Peptides (AMPs) with Significant Inhibitory Effect on Multidrug Resistant Strain of Salmonella Typhimurium","volume":"51","author":"Aamra","year":"2021","journal-title":"Synth. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1002\/ejoc.201801764","article-title":"Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus Anthracis","volume":"2019","author":"Dias","year":"2019","journal-title":"Eur. J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114640","DOI":"10.1016\/j.ejmech.2022.114640","article-title":"Pharmaceutical Nanotechnology: Antimicrobial Peptides as Potential New Drugs against WHO List of Critical, High, and Medium Priority Bacteria","volume":"241","author":"Rodrigues","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112699","DOI":"10.1016\/j.ejmech.2020.112699","article-title":"New One-Pot Synthesis of Anti-Tuberculosis Compounds Inspired on Isoniazid","volume":"208","author":"Ghiano","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s00044-011-9662-9","article-title":"Isonicotinic Acid Hydrazide Derivatives: Synthesis, Antimicrobial Activity, and QSAR Studies","volume":"21","author":"Judge","year":"2012","journal-title":"Med. Chem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1016\/j.ejmech.2010.02.006","article-title":"Synthesis and Antimicrobial Activity of Cholic Acid Hydrazone Analogues","volume":"45","author":"Rasras","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-695X.1998.tb01161.x","article-title":"Synergistic Activities of Antituberculous Drugs with Cerulenin and Trans-Cinnamic Acid against Mycobacterium Tuberculosis","volume":"21","author":"Rastogi","year":"1998","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00044-010-9528-6","article-title":"Synthesis and Antibacterial, Antifungal Activities of Some 2r,4c-Diaryl-3-Azabicyclo[3.3.1]Nonan-9-One-4-Aminobenzoyl Hydrazones","volume":"21","author":"Xaiver","year":"2012","journal-title":"Med. Chem. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12429","DOI":"10.1021\/acs.jmedchem.0c00748","article-title":"Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-immunol-030409-101229","article-title":"Innate Antifungal Immunity: The Key Role of Phagocytes","volume":"29","author":"Brown","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112645","DOI":"10.1016\/j.ejmech.2020.112645","article-title":"Design, Synthesis and Bioactivity Evaluation of Novel Arylalkene-Amide Derivatives as Dual-Target Antifungal Inhibitors","volume":"205","author":"Sun","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.ejmech.2019.07.003","article-title":"Antifungal Activity, Mode of Action Variability, and Subcellular Distribution of Coumarin-Based Antifungal Azoles","volume":"179","author":"Elias","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1128\/CMR.12.1.40","article-title":"Current and Emerging Azole Antifungal Agents","volume":"12","author":"Sheehan","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1080\/10426500601047016","article-title":"Synthesis and Antimicrobial Activity of Some 2-(Benzo[d]Oxazol\/Benzo[d]Imidazol-2-Ylthio)-N-(9 H-Fluoren-9-Yl)Acetamide Derivatives","volume":"182","author":"Kaplancikli","year":"2007","journal-title":"Phosphorus. Sulfur. Silicon Relat. Elem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.1016\/j.bmcl.2015.10.057","article-title":"New INH-Pyrazole Analogs: Design, Synthesis and Evaluation of Antitubercular and Antibacterial Activity","volume":"25","author":"Nayak","year":"2015","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1021\/cb300331z","article-title":"Structure\u2013Activity Relationship of a Broad-Spectrum Insect Odorant Receptor Agonist","volume":"7","author":"Taylor","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ejmech.2014.04.077","article-title":"Design, Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity","volume":"81","author":"Martins","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e0022120","DOI":"10.1128\/cmr.00221-20","article-title":"Environmental, Microbiological, and Immunological Features of Bacterial Biofilms Associated with Implanted Medical Devices","volume":"35","author":"Caldara","year":"2022","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the Emerging Threat of Antifungal Resistance to Human Health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"114161","DOI":"10.1016\/j.ejmech.2022.114161","article-title":"Synthetic Approaches and Structural Diversity of Triazolylbutanols Derived from Voriconazole in the Antifungal Drug Development","volume":"231","author":"Ghobadi","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/AAC.44.9.2373-2381.2000","article-title":"Potent Synergism of the Combination of Fluconazole and Cyclosporine in Candida Albicans","volume":"44","author":"Marchetti","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1177\/1091581811423582","article-title":"Trends in Excipient Safety Evaluation","volume":"30","author":"Osterberg","year":"2011","journal-title":"Int. J. Toxicol."},{"key":"ref_50","first-page":"e50166","article-title":"Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of PH-Responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs","volume":"73","author":"Evans","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13206","DOI":"10.1038\/s41598-020-69995-9","article-title":"Correlation between Hemolytic Activity, Cytotoxicity and Systemic in Vivo Toxicity of Synthetic Antimicrobial Peptides","volume":"10","author":"Greco","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Catalano, A., Iacopetta, D., Ceramella, J., Scumaci, D., Giuzio, F., Saturnino, C., Aquaro, S., Rosano, C., and Sinicropi, M.S. (2022). Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies. Molecules, 27.","DOI":"10.3390\/molecules27030616"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Terreni, M., Taccani, M., and Pregnolato, M. (2021). New Antibiotics for Multidrug-Resistant Bacterial Strains: Latest Research Developments and Future Perspectives. Molecules, 26.","DOI":"10.3390\/molecules26092671"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1038\/s41598-021-82550-4","article-title":"New Combination Approaches to Combat Methicillin-Resistant Staphylococcus Aureus (MRSA)","volume":"11","author":"Sharaf","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Glen, K.A., and Lamont, I.L. (2021). \u03b2-Lactam Resistance in Pseudomonas Aeruginosa: Current Status, Future Prospects. Pathogens, 10.","DOI":"10.3390\/pathogens10121638"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e01134-18","DOI":"10.1128\/AAC.01134-18","article-title":"Crystal Structures of Full-Length Lanosterol 14\u03b1-Demethylases of Prominent Fungal Pathogens Candida Albicans and Candida Glabrata Provide Tools for Antifungal Discovery","volume":"62","author":"Keniya","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00894-010-0889-z","article-title":"Biological and Docking Studies of Topoisomerase IV Inhibition by Thiosemicarbazides","volume":"17","author":"Siwek","year":"2011","journal-title":"J. Mol. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1021\/jm300309a","article-title":"Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3\u03b1","volume":"55","author":"Kramer","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s10593-020-02698-1","article-title":"Reaction of 3-[(Alkylsulfanyl)Methyl]Pentane-2,4-Diones with Nicotinic Hydrazide","volume":"56","author":"Baeva","year":"2020","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1021\/ol5006449","article-title":"Pd-Catalyzed Oxidative Annulation of Hydrazides with Isocyanides: Synthesis of 2-Amino-1,3,4-Oxadiazoles","volume":"16","author":"Fang","year":"2014","journal-title":"Org. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00044-013-0715-0","article-title":"Synthesis of Hydrophobic N-Acylated Isonicotinic Acid Hydrazide Derivatives as Potential Enoyl\u2013Acyl Carrier Protein Reductase (InhA) Inhibitors","volume":"23","author":"Parumasivam","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1128\/AAC.41.3.535","article-title":"Reversible Fluconazole Resistance in Candida Albicans: A Potential in Vitro Model","volume":"41","author":"Calvet","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1128\/JCM.43.5.2155-2162.2005","article-title":"Antifungal Susceptibilities of Candida Species Causing Vulvovaginitis and Epidemiology of Recurrent Cases","volume":"43","author":"Richter","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1476644","DOI":"10.1080\/20002297.2018.1476644","article-title":"Fluconazole Impacts the Extracellular Matrix of Fluconazole-Susceptible and -Resistant Candida Albicans and Candida Glabrata Biofilms","volume":"10","author":"Panariello","year":"2018","journal-title":"J. Oral Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1128\/JCM.00865-06","article-title":"Candida Guilliermondii, an Opportunistic Fungal Pathogen with Decreased Susceptibility to Fluconazole: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program","volume":"44","author":"Pfaller","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_66","unstructured":"CLSI, Clinical and Laboratory Standards Institute (formerly NCCLS, National Committee for Clinical and Laboratory Standards) (2002). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Approved Standard M27-A2, National Committee for Clinical and Laboratory Standards."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Montagna, M.T., Lovero, G., Coretti, C., Martinelli, D., De Giglio, O., Iatta, R., Balbino, S., Rosato, A., and Caggiano, G. (2015). Susceptibility to Echinocandins of Candida spp. Strains Isolated in Italy Assessed by European Committee for Antimicrobial Susceptibility Testing and Clinical Laboratory Standards Institute Broth Microdilution Methods. BMC Microbiol., 15.","DOI":"10.1186\/s12866-015-0442-4"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e01961-16","DOI":"10.1128\/AAC.01961-16","article-title":"SCY-078 Is Fungicidal against Candida Species in Time-Kill Studies","volume":"61","author":"Scorneaux","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3109\/03091902.2016.1153741","article-title":"An Approach to Measuring RBC Haemolysis and Profiling RBC Mechanical Fragility","volume":"40","author":"Alfano","year":"2016","journal-title":"J. Med. Eng. Technol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1128\/AAC.49.9.3734-3742.2005","article-title":"Multidrug-Resistant Pseudomonas Aeruginosa Strain That Caused an Outbreak in a Neurosurgery Ward and Its Aac(6\u2032)-Iae Gene Cassette Encoding a Novel Aminoglycoside Acetyltransferase","volume":"49","author":"Sekiguchi","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00064-13","DOI":"10.1128\/mBio.00064-13","article-title":"Characterization of Aeromonas Hydrophila Wound Pathotypes by Comparative Genomic and Functional Analyses of Virulence Genes","volume":"4","author":"Grim","year":"2013","journal-title":"mBio"},{"key":"ref_72","unstructured":"Cockerill, F.R. (2012). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Clinical and Laboratory Standards Institute. [9th ed.]."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/1\/212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:51:49Z","timestamp":1760147509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/1\/212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,26]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["molecules28010212"],"URL":"https:\/\/doi.org\/10.3390\/molecules28010212","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,26]]}}}