{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:58:01Z","timestamp":1775894281417,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2013,5,15]],"date-time":"2013-05-15T00:00:00Z","timestamp":1368576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Eighteen (3R) and (3R,4R)-N-phenyl-, N-phenylalkyl and N-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with  A. fumigatus. This environmentally friendly, clean and economical procedure was performed by the whole-cell fungal bioconversion methodology. Their corresponding eighteen racemic succinimides were prepared instead by synthetic methods. Both, the racemic and the chiral succinimides were tested simultaneously by the microbroth dilution method of CLSI against a panel of human opportunistic pathogenic fungi of clinical importance. Chiral succinimides showed higher antifungal activity than the corresponding racemic ones and the differences in activity were established by statistical methods. The bottlenecks for developing chiral drugs are how to obtain them through a low-cost procedure and with high enantiomeric excess. Results presented here accomplish both these objectives, opening an avenue for the development of asymmetric succinimides as new antifungal drugs for pharmaceutical use.<\/jats:p>","DOI":"10.3390\/molecules18055669","type":"journal-article","created":{"date-parts":[[2013,5,15]],"date-time":"2013-05-15T12:29:39Z","timestamp":1368620979000},"page":"5669-5683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effects of Chirality on the Antifungal Potency of Methylated Succinimides Obtained by Aspergillus fumigatus Biotransformations. Comparison with Racemic Ones"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4271-1690","authenticated-orcid":false,"given":"Maximiliano","family":"Sortino","sequence":"first","affiliation":[{"name":"Pharmacognosy Area, Faculty of Biochemical and Pharmaceutical Sciences,  National University of Rosario, Suipacha 531, 2000-Rosario, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agustina","family":"Postigo","sequence":"additional","affiliation":[{"name":"Pharmacognosy Area, Faculty of Biochemical and Pharmaceutical Sciences,  National University of Rosario, Suipacha 531, 2000-Rosario, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-5500","authenticated-orcid":false,"given":"Susana","family":"Zacchino","sequence":"additional","affiliation":[{"name":"Pharmacognosy Area, Faculty of Biochemical and Pharmaceutical Sciences,  National University of Rosario, Suipacha 531, 2000-Rosario, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0968-0896(95)00024-B","article-title":"Design, synthesis and biological evaluation of succinimide derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinas","volume":"3","author":"Groutas","year":"1995","journal-title":"Bioorg. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1016\/S0960-894X(02)00622-4","article-title":"Succinimide hydroxamic acids as potent inhibitors of histone deacetylase (HDAC)","volume":"12","author":"Curtin","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/S0040-4039(02)02781-8","article-title":"Biologically interesting chiral 3,4-disubstituted pyrrolidines from optically active hydroxycitric acid lactones","volume":"44","author":"Ibnusaud","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1016\/j.tet.2005.03.099","article-title":"Hirsutellones A\u2013E, antimycobacterial alkaloids from the insect pathogenic fungus Hirsutella nivea BCC 2594","volume":"61","author":"Isaka","year":"2005","journal-title":"Tetrahedron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1016\/j.bmc.2006.06.043","article-title":"Cytotoxic labdane alkaloids from an ascidian Lissoclinum sp.: Isolation, structure elucidation, and structure-activity relationship","volume":"14","author":"Uddin","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/asia.201200684","article-title":"Asymmetric organocatalytic addition reactions of maleimides: A promising approach towards the synthesis of chiral succinimide derivatives","volume":"8","author":"Chauhan","year":"2013","journal-title":"Chem. Asian J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1021\/ja00248a055","article-title":"Andrimid, a new peptide antibiotic produced by an intracellular bacterial symbiont isolated from a brown planthopper","volume":"109","author":"Fredenhagen","year":"1987","journal-title":"J. Am. Chem. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1002\/chem.200701505","article-title":"Highly enantio- and s-trans C=C bond selective catalytic hydrogenation of cyclic enones: Alternative synthesis of (\u2212)-menthol","volume":"14","author":"Ohshima","year":"2008","journal-title":"Chem. Eur. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.tetasy.2009.02.009","article-title":"Stereoselective biotransformations using fungi as biocatalysts","volume":"20","author":"Borges","year":"2009","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bej.2009.05.009","article-title":"Enantioselective whole-cell biotransformation of acetophenone to S-phenylethanol by Rhodotorula glutinis: Part I. Product formation kinetics and feeding strategies in aqueous media","volume":"46","author":"Livingston","year":"2009","journal-title":"Biochem. Eng. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1021\/cs200219b","article-title":"Biocatalysis: Synthesis of key intermediates for development of pharmaceuticals","volume":"1","author":"Patel","year":"2011","journal-title":"ACS Catal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1039\/c000408c","article-title":"Pharmacologically active compounds in the environment and their chirality","volume":"39","year":"2010","journal-title":"Chem. Soc. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.tetasy.2009.04.009","article-title":"Highly enantioselective reduction of the C-C double bond of N-phenyl-2-methyl-and N-phenyl-2,3-dimethyl-maleimides by fungal strains","volume":"20","author":"Sortino","year":"2009","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.tetasy.2010.02.017","article-title":"Efficient asymmetric hydrogenation of the C-C double bond of 2-methyl-and 2,3-dimethyl-N-phenylalkylmaleimides by Aspergillus fumigatus","volume":"21","author":"Sortino","year":"2010","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/jac\/37.1.7","article-title":"Drug chirality: A consideration of the significance of the stereochemistry of antimicrobial agents","volume":"37","author":"Hutt","year":"1996","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Whittall, J., and Sutton, P. (2012). Practical Methods for Biocatalysis and Biotransformations 2, Wiley & Sons.","DOI":"10.1002\/9781119943426"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Balenovi\u0107, K., and Bregant, N. (1965). Correlation of the configurations of \u03b1-methyl-\u03b2-alanine and methylsuccinic acid. J. Chem. Soc., 5131\u20135132.","DOI":"10.1039\/JR9650005131"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/j.tetasy.2006.06.030","article-title":"Asymmetric hydrogenation of the C-C double bond of 1-and 1,2-methylated maleimides with cultured suspension cells of Marchantia polymorpha","volume":"17","author":"Hegazy","year":"2006","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: A persistent public health problem","volume":"20","author":"Pfaller","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/jhin.2002.1278","article-title":"Systemic mycoses in the immunocompromised host: An update in antifungal therapy","volume":"53","author":"Kontoyiannis","year":"2003","journal-title":"J. Hosp. Inf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S1473-3099(03)00802-8","article-title":"Treatment of opportunistic mycoses: How long is long enough?","volume":"3","author":"Singh","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.8.2.240","article-title":"The dermatophytes","volume":"8","author":"Weitzman","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","unstructured":"(2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard M27-A3, CLSI. [3rd ed.]."},{"key":"ref_24","unstructured":"(2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard M38-A2, CLSI. [2nd ed.]."},{"key":"ref_25","unstructured":"Stokes, M., Davis, Ch., and Koch, G. (2000). Categorical Data Analysis Using the SAS System, SAS Institute. [2nd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1021\/ol051504a","article-title":"Organocatalytic ring expansion of \u03b2-lactams to \u03b3-lactams through a novel N1-C4 bond cleavage. Direct synthesis of enantiopure succinimide derivatives","volume":"7","author":"Alcaide","year":"2005","journal-title":"Org. Lett."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/5\/5669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:46:44Z","timestamp":1760219204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/5\/5669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,15]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,5]]}},"alternative-id":["molecules18055669"],"URL":"https:\/\/doi.org\/10.3390\/molecules18055669","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,15]]}}}