{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:34:47Z","timestamp":1781634887591,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir","award":["internal grant"],"award-info":[{"award-number":["internal grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Based on a set of six vector properties, the partial correlation diagram is calculated for a set of 28 S-alkylcysteine diazomethyl- and chloromethyl-ketone derivatives. Those with the greatest antileukemic activity in the same class correspond to high partial correlations. A periodic classification is performed based on information entropy. The first four characteristics denote the group, and the last two indicate the period. Compounds in the same period and, especially, group present similar properties. The most active substances are situated at the bottom right. Nine classes are distinguished. The principal component analysis of the homologous compounds shows five subclasses included in the periodic classification. Linear fits of both antileukemic activities and stability are good. They are in agreement with the principal component analysis. The variables that appear in the models are those that show positive loading in the principal component analysis. The most important properties to explain the antileukemic activities (50% inhibitory concentration Molt-3 T-lineage acute lymphoblastic leukemia minus the logarithm of 50% inhibitory concentration Nalm-6 B-lineage acute lymphoblastic leukemia and stability k) are ACD logD, surface tension and number of violations of Lipinski\u2019s rule of five. After leave-m-out cross-validation, the most predictive model for cysteine diazomethyl- and chloromethyl-ketone derivatives is provided.<\/jats:p>","DOI":"10.3390\/molecules26010235","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T10:35:12Z","timestamp":1609842912000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Classification of Congeneric and QSAR of Homologous Antileukemic S\u2013Alkylcysteine Ketones"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-880X","authenticated-orcid":false,"given":"Gloria","family":"Castellano","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Traslacional San Alberto Magno (CITSAM), Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir, Guillem de Castro-94, E-46001 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Escuela de Doctorado, Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir, E-46008 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8534-208X","authenticated-orcid":false,"given":"Francisco","family":"Torrens","sequence":"additional","affiliation":[{"name":"Institut Universitari de Ci\u00e8ncia Molecular, Universitat de Val\u00e8ncia, Edifici d\u2019Instituts de Paterna, P. O. Box 22085, E-46071 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","unstructured":"Uckun, F.M., Narla, R.M., and Perry, D.A. (2001). Parker Hughes Institute. Alkyl Ketones as Potent Anti-Cancer Agents. (Patent US6251882B1)."},{"key":"ref_4","unstructured":"Uckun, F.M., Narla, R.M., and Perry, D.A. (2001). Parker Hughes Institute. Alkyl Ketones as Potent Anti-Cancer Agents. (Patent CA2336108A1)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0960-894X(00)00046-9","article-title":"Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity","volume":"10","author":"Perrey","year":"2000","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0960-894X(00)00047-0","article-title":"The S-alkyl chain length as a determinant of the anti-leukemic activity of cysteine chloromethyl ketone compounds","volume":"10","author":"Perrey","year":"2000","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1081\/DDC-120002447","article-title":"A degradation study of a series of chloromethyl and diazomethyl ketone anti-leukemic agents","volume":"28","author":"Kotchevar","year":"2002","journal-title":"Drug Develop. Ind. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1381-1177(02)00041-3","article-title":"Biocatalytic oxidation of S-alkylcysteine derivatives by chloroperoxidase and Beauveria species","volume":"17","author":"Holland","year":"2002","journal-title":"J. Mol. Catal. B Enzym."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/chem.201602694","article-title":"The cysteine S-alkylation reaction as a synthetic method to covalently modify peptide sequences","volume":"23","author":"Calce","year":"2017","journal-title":"Chem. Eur. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.2174\/1568026618666171211145846","article-title":"QSAR of natural sesquiterpene lactones as inhibitors of Myb-dependent gene expression","volume":"17","author":"Castellano","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2174\/1570163816666190101113434","article-title":"Structure\u2013activity relationships of cytotoxic lactones as inhibitors and mechanisms of action","volume":"17","author":"Torrens","year":"2020","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_12","first-page":"231","article-title":"Structural indicators and its relation to antioxidant properties of Posidonia oceanica (L.) Delile","volume":"67","author":"Castellano","year":"2012","journal-title":"MATCH Commun. Math. Comput. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.phytochem.2013.03.024","article-title":"Classification of flavonoid compounds by using entropy of information theory","volume":"93","author":"Castellano","year":"2013","journal-title":"Phytochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.phytochem.2013.10.010","article-title":"Classification of stilbenoid compounds by entropy of artificial intelligence","volume":"97","author":"Castellano","year":"2014","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12891","DOI":"10.3390\/ijms160612891","article-title":"Quantitative structure\u2013antioxidant activity models of isoflavonoids: A theoretical study","volume":"16","author":"Castellano","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.phytochem.2015.05.008","article-title":"Information entropy-based classification of triterpenoids and steroids from Ganoderma","volume":"116","author":"Castellano","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_17","unstructured":"Shaw, P.J.A. (2003). Multivariate Statistics for the Environmental Sciences, Hodder-Arnold."},{"key":"ref_18","first-page":"49","article-title":"QSAR study on benzenesulfonamide ionization constant: Physicochemical approach using surface tension","volume":"14","author":"Thakur","year":"2005","journal-title":"Arch. Org. Chem."},{"key":"ref_19","first-page":"48","article-title":"Neural network learning and statistics","volume":"4","author":"White","year":"1989","journal-title":"AI Expert"},{"key":"ref_20","unstructured":"Kullback, S. (1959). Information Theory and Statistics, Wiley."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Iordache, O. (2011). Modeling Multi-Level Systems, Springer.","DOI":"10.1007\/978-3-642-17946-4"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Iordache, O. (2012). Self-Evolvable Systems: Machine Learning in Social Media, Springer.","DOI":"10.1007\/978-3-642-28882-1"},{"key":"ref_23","unstructured":"IMSL (1989). Integrated Mathematical Statistical Library (IMSL), IMSL."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1023\/A:1010924406885","article-title":"Fast computation of cross-validated properties in full linear leave-many-out procedures","volume":"29","year":"2001","journal-title":"J. Math. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:07:06Z","timestamp":1760159226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,5]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["molecules26010235"],"URL":"https:\/\/doi.org\/10.3390\/molecules26010235","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,5]]}}}