{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:48:52Z","timestamp":1778273332250,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Cear\u00e1 (FUNCAP)","award":["406522\/2021-9-1"],"award-info":[{"award-number":["406522\/2021-9-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Cear\u00e1 (FUNCAP)","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Cear\u00e1 (FUNCAP)","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["406522\/2021-9-1"],"award-info":[{"award-number":["406522\/2021-9-1"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["406522\/2021-9-1"],"award-info":[{"award-number":["406522\/2021-9-1"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]},{"name":"FUNCAP-UNIVERSAL","award":["406522\/2021-9-1"],"award-info":[{"award-number":["406522\/2021-9-1"]}]},{"name":"FUNCAP-UNIVERSAL","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"FUNCAP-UNIVERSAL","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]},{"name":"CNPq-PQ","award":["406522\/2021-9-1"],"award-info":[{"award-number":["406522\/2021-9-1"]}]},{"name":"CNPq-PQ","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"CNPq-PQ","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Nanoemulsions (NEs) possess properties that enhance the solubility, bioavailability and therapeutic efficacy of drugs. Chalcones are compounds known for their antifungal properties. In this study, we evaluated different emulsification techniques to create alginate nanoemulsions containing chalcone (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB4OCH3). Our goal was to develop an antifungal formulation targeting Candida albicans strains. Methods: Ultrasound and ultrasound combined with high-speed homogenization techniques were used to prepare alginate-stabilized nanoemulsions. Particle size, zeta potential and encapsulation efficiency were evaluated. Additionally, in vitro release studies were conducted. Results: The combined emulsification technique produced stable nanoparticles with high encapsulation efficiency and antifungal activity, with a minimum inhibitory concentration of 8.75 \u03bcg\/mL for the nanoemulsions compared to 312 \u00b5g\/mL for free DB4OCH3. NEs\u2019 effectiveness can be attributed to their ability to form nanodroplets efficiently, facilitating the solubilization of the chalcone in the oily phase. The particle size varied between 195.70 \u00b1 2.69 and 243.40 \u00b1 4.49 nm, with an increase in chalcone concentration leading to larger particle sizes. The zeta potential showed values from \u221291.77 \u00b1 5.58 to \u221276.90 \u00b1 4.44 mV. The UHS-7 sample exhibited an encapsulation efficiency of 92.10% \u00b1 0.77, with a controlled in vitro release of 83% after 34 h. Molecular docking simulations showed that the aromatic nature of DB4OCH3 resulted in the formation of apolar interactions with aromatic residues located in the active site of the TMK, as observed in their respective co-crystallized inhibitors, within an affinity energy range that enables optimum specificity of the ligand for these two pathways. Pharmacokinetic analyses indicated high passive cell permeability and low hepatic clearance, and phase I metabolism reduces its oral bioavailability and metabolic stability, suggesting a promising active ingredient as an oral drug with control of the daily oral dose administered. Conclusions: The combined nanoemulsification technique led to the formation of finely dispersed nanodroplets that favored the solubilization of the chalcone in the oil phase, which led to a better performance in the antifungal properties. DB4OCH3 shows promise as an oral drug with controlled dosing.<\/jats:p>","DOI":"10.3390\/ph17111442","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T07:47:18Z","timestamp":1730101638000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Emulsification Techniques to Optimize the Properties of Chalcone Nanoemulsions for Antifungal Applications"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7662-1653","authenticated-orcid":false,"given":"Joice Farias do","family":"Nascimento","sequence":"first","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-2739","authenticated-orcid":false,"given":"Flavia Oliveira Monteiro da Silva","family":"Abreu","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taysse","family":"Holanda","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8865-5954","authenticated-orcid":false,"given":"Raquel","family":"Oliveira dos Santos Fontenelle","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falio C\u00e9sar Sousa","family":"Prado","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-8775","authenticated-orcid":false,"given":"Emmanuel Silva","family":"Marinho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0929-4565","authenticated-orcid":false,"given":"Matheus Nunes","family":"da Rocha","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-0789","authenticated-orcid":false,"given":"Jesyka Mac\u00eado","family":"Guedes","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural Sciences, Cear\u00e1 State University, Fortaleza 60714-903, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Coelho","family":"Cavalcanti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-160, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2784-0013","authenticated-orcid":false,"given":"Wesley Lyeverton Correia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Cear\u00e1, Fortaleza 60430-160, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcia Machado","family":"Marinho","sequence":"additional","affiliation":[{"name":"Center for Exact Sciences and Technology, Vale do Acara\u00fa University, Sobral 62040-370, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-164X","authenticated-orcid":false,"given":"Helcio Silva dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Center for Exact Sciences and Technology, Vale do Acara\u00fa University, Sobral 62040-370, CE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.3109\/10717544.2015.1092619","article-title":"Development of an Optimized Hyaluronic Acid-Based Lipidic Nanoemulsion Co-Encapsulating Two Polyphenols for Nose to Brain Delivery","volume":"23","author":"Nasr","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.2217\/nnm-2018-0088","article-title":"Nanoemulsions in Drug Delivery: Formulation to Medical Application","volume":"13","author":"Tayeb","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1111\/1541-4337.12604","article-title":"Application of Nanoemulsion-Based Approaches for Improving the Quality and Safety of Muscle Foods: A Comprehensive Review","volume":"19","author":"Das","year":"2020","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lugani, Y., Sooch, B.S., Singh, P., and Kumar, S. (2020). Nanobiotechnology Applications in Food Sector and Future Innovations, Elsevier Inc.","DOI":"10.1016\/B978-0-12-819813-1.00008-6"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Maurya, A., Singh, V.K., Das, S., Prasad, J., Kedia, A., Upadhyay, N., Dubey, N.K., and Dwivedy, A.K. (2021). Essential Oil Nanoemulsion as Eco-Friendly and Safe Preservative: Bioefficacy Against Microbial Food Deterioration and Toxin Secretion, Mode of Action, and Future Opportunities. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.751062"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00396-020-04653-0","article-title":"Encapsulation of Caffeine in Polysaccharide Oil-Core Nanocapsules","volume":"298","author":"Milkova","year":"2020","journal-title":"Colloid Polym. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ayala-Fuentes, J.C., and Chavez-Santoscoy, R.A. (2021). Nanotechnology as a Key to Enhance the Benefits and Improve the Bioavailability of Flavonoids in the Food Industry. Foods, 10.","DOI":"10.3390\/foods10112701"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1080\/17425255.2017.1360279","article-title":"Curcumin as a Clinically-Promising Anti-Cancer Agent: Pharmacokinetics and Drug Interactions","volume":"13","author":"Adiwidjaja","year":"2017","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00396-022-04998-8","article-title":"Encapsulation of Curcumin in Gliadin-Pectin in a Core\u2013Shell Nanostructure for Efficient Delivery of Curcumin to Cancer Cells In Vitro","volume":"300","author":"Banaee","year":"2022","journal-title":"Colloid Polym. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1007\/s00396-021-04892-9","article-title":"Amphipathic Methoxypolyethylene Glycol-Curcumin Conjugate as Effective Drug Delivery System Useful for Colonic Diseases","volume":"299","author":"Goyal","year":"2021","journal-title":"Colloid Polym. Sci."},{"key":"ref_11","unstructured":"Mendes, E.V. (2011). As Redes de Aten\u00e7\u00e3o \u00e0 Sa\u00fade, Organiza\u00e7\u00e3o Pan-Americana da Sa\u00fade."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Monteiro-Neto, V., de Souza, C.D., Gonzaga, L.F., da Silveira, B.C., Sousa, N.C.F., Pontes, J.P., Santos, D.M., Martins, W.C., Pessoa, J.F.V., and Carvalho J\u00fanior, A.R. (2020). naldehyde Potentiates the Antimicrobial Actions of Ciprofloxacin against Staphylococcus aureus and Escherichia coli. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232987"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jasim, H.A., Nahar, L., Jasim, M.A., Moore, S.A., Ritchie, K.J., and Sarker, S.D. (2021). Chalcones: Synthetic Chemistry Follows Where Nature Leads. Biomolecules, 11.","DOI":"10.3390\/biom11081203"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s11030-019-09967-y","article-title":"Design, Synthesis, Antifungal Activity, and Structure\u2013Activity Relationship Studies of Chalcones and Hybrid Dihydrochromane\u2013Chalcones","volume":"24","author":"Mellado","year":"2020","journal-title":"Mol. Divers."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"582079","DOI":"10.1155\/2013\/582079","article-title":"Synthesis, Characterization, and Biological Activity of 4-(2-Hydroxy-5-(Aryl-Diazenyl)Phenyl)-6-(Aryl)Pyrimidin-2-Ols Derivatives","volume":"2013","author":"Pandhurnekar","year":"2013","journal-title":"Org. Chem. Int."},{"key":"ref_16","first-page":"1","article-title":"Thermodynamic and Kinetic Stability of Cosmetic Nanoemulsions","volume":"Volume 2024","author":"Ajayi","year":"2024","journal-title":"Design and Applications of Self-Assembly Aggregates\u2014From Micelles to Nanoemulsions"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7367","DOI":"10.1007\/s00289-023-05069-w","article-title":"Formulation of nanoemulsions enriched with chalcone-based compounds: Formulation process, physical stability, and antimicrobial effect","volume":"81","author":"Abreu","year":"2024","journal-title":"Polym. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2217\/fmb-2019-0095","article-title":"Antifungal activity of 2\u2032-hydroxychalcone loaded in nanoemulsion against Paracoccidioides spp.","volume":"15","author":"Singulani","year":"2020","journal-title":"Future Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"626","DOI":"10.4236\/jbnb.2011.225075","article-title":"Current State of Nanoemulsions in Drug Delivery","volume":"2011","author":"Lovelyn","year":"2011","journal-title":"J. Biomater. Nanobiotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.tifs.2020.11.018","article-title":"Ultrasound Modified Polysaccharides: A Review of Structure, Physicochemical Properties, Biological Activities and Food Applications","volume":"107","author":"Cui","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Maphosa, Y., and Jideani, V.A. (2018). Factors Affecting the Stability of Emulsions Stabilised by Biopolymers. Science and Technology Behind Nanoemulsions, IntechOpen.","DOI":"10.5772\/intechopen.75308"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12302-021-00524-9","article-title":"Nanoparticles Engineered from Endophytic Fungi (Botryosphaeria rhodina) against ESBL-Producing Pathogenic Multidrug-Resistant E. coli","volume":"33","author":"Akther","year":"2021","journal-title":"Environ. Sci. Eur."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s10876-019-01694-6","article-title":"Green Nanocolloids Control Multi Drug Resistant Pathogenic Bacteria","volume":"31","author":"Ranjani","year":"2020","journal-title":"J. Clust. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jddst.2017.04.004","article-title":"Evaluation of the Impact of Critical Quality Attributes and Critical Process Parameters on Quality and Stability of Parenteral Nutrition Nanoemulsions","volume":"39","author":"Knez","year":"2017","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1517\/17425247.2012.696605","article-title":"Nanoemulsions as Potential Vehicles for Transdermal and Dermal Delivery of Hydrophobic Compounds: An Overview","volume":"9","author":"Shakeel","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12871","DOI":"10.1039\/C8NR02278J","article-title":"Characterization techniques for nanoparticles: Comparison and complementarity upon studying nanoparticle properties1","volume":"10","author":"Mourdikoudis","year":"2018","journal-title":"Nanoscale"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4103\/2231-4040.161507","article-title":"Chalcone Derivatives as Potential Antifungal Agents: Synthesis, and Antifungal Activity","volume":"6","author":"Gupta","year":"2015","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5373","DOI":"10.1021\/jf300609p","article-title":"Improving the Oral Bioavailability of Curcumin Using Novel Organogel-Based Nanoemulsions","volume":"60","author":"Yu","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ali, M., Khan, N.R., Subhan, Z., Mehmood, S., Amin, A., Rabbani, I., Rehman, F.U., Basit, H.M., Syed, H.K., and Khan, I.U. (2022). Novel Curcumin-Encapsulated \u03b1 -Tocopherol Nanoemulsion System and Its Potential Application for Wound Healing in Diabetic Animals. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/7669255"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1080\/10412905.2022.2107100","article-title":"Preparation, Characterization, and Antimicrobial Activity of Cinnamon Essential Oil and Cinnamaldehyde Nanoemulsions","volume":"34","author":"Badr","year":"2022","journal-title":"J. Essent. Oil Res."},{"key":"ref_31","first-page":"285","article-title":"Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone","volume":"12","author":"Holanda","year":"2024","journal-title":"J. Renew. Mater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5031577","DOI":"10.1155\/2022\/5031577","article-title":"Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation","volume":"2022","author":"Salehi","year":"2022","journal-title":"J. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"MR17","DOI":"10.1116\/1.2815690","article-title":"Nanomaterials and Nanoparticles: Sources and Toxicity","volume":"2","author":"Buzea","year":"2007","journal-title":"Biointerphases"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9954443","DOI":"10.1155\/2021\/9954443","article-title":"Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology","volume":"2021","author":"Egbuna","year":"2021","journal-title":"J. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jddst.2018.03.004","article-title":"Cross-Linked, Cyclodextrin-Based Nanosponges for Curcumin Delivery\u2014Physicochemical Characterization, Drug Release, Stability and Cytotoxicity","volume":"45","author":"Pushpalatha","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mann, G., Chauhan, K., Kumar, V., Daksh, S., Kumar, N., Thirumal, M., and Datta, A. (2022). Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-\u03b2-Targeting Probe. Front. Med., 9.","DOI":"10.3389\/fmed.2022.813465"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, B., Teng, Z., Li, X., Lu, G., Deng, X., Niu, X., and Wang, J. (2017). Chalcone Attenuates Staphylococcus aureus Virulence by Targeting Sortase A and Alpha-Hemolysin. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01715"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.apsb.2015.07.003","article-title":"Insoluble Drug Delivery Strategies: Review of Recent Advances and Business Prospects","volume":"5","author":"Kalepu","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_39","first-page":"217","article-title":"Kinetic Modeling on Drug Release from Controlled Drug Delivery Systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm.-Drug Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.foodhyd.2016.04.023","article-title":"Effects of Environmental Factors on the Physical Stability of Pickering-Emulsions Stabilized by Chitosan Particles","volume":"60","author":"Mwangi","year":"2016","journal-title":"Food Hydrocoll."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"76600","DOI":"10.1039\/C6RA17788C","article-title":"Benzimidazole Based Pt(II) Complexes with Better Normal Cell Viability than Cisplatin: Synthesis, Substitution Behavior, Cytotoxicity, DNA Binding and DFT Study","volume":"6","author":"Mitra","year":"2016","journal-title":"RSC Adv."},{"key":"ref_42","first-page":"279","article-title":"Medida de Viscosidade pelo M\u00e9todo de Ostwald: Um Experimento Did\u00e1tico","volume":"17","author":"Almeida","year":"1995","journal-title":"Rev. Bras. Ensino F\u00eds."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0742-8413(96)00107-7","article-title":"Chemical and Pharmacological Characterization of Halitoxin from Amphimedon Viridis (Porifera) from the Southeastern Brazilian Coast","volume":"115","author":"Berlinck","year":"1996","journal-title":"Comp. Biochem. Physiol.-C Pharmacol. Toxicol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1093\/jac\/dkm066","article-title":"Chemical Composition, Toxicological Aspects and Antifungal Activity of Essential Oil from Lippia sidoides Cham","volume":"59","author":"Fontenelle","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","unstructured":"(2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts (Standard No. CLSI M27)."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.bmcl.2012.11.032","article-title":"Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity","volume":"23","author":"Tari","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104365","DOI":"10.1016\/j.micpath.2020.104365","article-title":"Virtual screening based on molecular docking of possible inhibitors of COVID-19 main protease","volume":"148","author":"Marinho","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1021\/cn100008c","article-title":"Villalobos, Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach to Enable Alignment of Druglike Properties","volume":"1","author":"Wager","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s10822-014-9744-0","article-title":"MLP Tools: A PyMOL plugin for using the molecular lipophilicity potential in computer-aided drug design","volume":"28","author":"Oberhauser","year":"2014","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"139124","DOI":"10.1016\/j.molstruc.2024.139124","article-title":"Synthesis, Vibrational Analysis, Thermal analysis, Quantum-chemical Calculation, Molecular Docking and Dynamics, DMPK and Evaluation of the Antichagasic Potential of a Fluorinated Chalcone","volume":"1318","author":"Nunes","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_52","first-page":"254","article-title":"In Silico Study in MPO and Molecular Docking of the Synthetic Drynaran Analogues Against the Chronic Tinnitus: Modulation of the M1 Muscarinic Acetylcholine Receptor","volume":"66","author":"Dantas","year":"2023","journal-title":"Mol. Biotechnol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:22:18Z","timestamp":1760113338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/11\/1442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ph17111442"],"URL":"https:\/\/doi.org\/10.3390\/ph17111442","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]}}}