{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:39:53Z","timestamp":1768873193544,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T00:00:00Z","timestamp":1516060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Due to its crucial role in DNA synthesis, thymidylate synthase (TS) has been considered as a potential therapeutic target. Inhibition of the enzyme is a promising strategy for the treatment of some hyperproliferative diseases, including infections. As TS species\u2010specific inhibitors would be able to distinguish between the host and the pathogens, developing highly selective inhibitors is of great clinical importance. TS is among the most highly conserved enzymes over evolutionary history, making the design of its species\u2010selective inhibitor significantly challenging. The chemical interaction space, governed by a set of non\u2010selective TS inhibitors, has been explored for human TS and its homologous proteins in both <jats:italic>Toxoplasma gondii<\/jats:italic> and <jats:italic>Escherichia coli<\/jats:italic> using proteochemometrics modeling (PCM). Validity, robustness, and prediction power of the PCM model have been assessed applying a diverse set of internal\/external validation approaches. Our PCM model has provided major structural information, which is indeed of great help to design new TS species\u2010specific inhibitors with the simultaneous inhibition ability toward both <jats:italic>T.\u00a0gondii<\/jats:italic> and <jats:italic>E.\u00a0coli<\/jats:italic>. To show applicability of the PCM model, new compounds have been designed based on structural information provided by the constructed model. Final results have been very promising with regard to selectivity ratios of the designed compounds for different TS isoforms, confirming the applicability of the PCM model.<\/jats:p>","DOI":"10.1111\/cbdd.13163","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T14:32:36Z","timestamp":1513607556000},"page":"1007-1016","source":"Crossref","is-referenced-by-count":11,"title":["Proteochemometric modeling of the origin of thymidylate synthase inhibition"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5061-3142","authenticated-orcid":false,"given":"Behnam","family":"Rasti","sequence":"first","affiliation":[{"name":"Department of Microbiology Faculty of Basic Sciences Lahijan Branch Islamic Azad University (IAU)  Lahijan Guilan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyyedeh Shirin","family":"Shahangian","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Sciences University of Guilan  Rasht Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(00)00249-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.6.1465"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti703"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.08.081"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-181"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-339"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci1000532"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci400369z"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci8000953"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1979"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12759"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/minf.201600102"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA02332D"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(02)00083-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm701052u"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"921.12","DOI":"10.1096\/fasebj.31.1_supplement.925.9","volume":"31","author":"Islam Z.","year":"2017","journal-title":"FASEB J."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11040"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.12.010"},{"key":"e_1_2_7_20_1","first-page":"1","volume":"7","author":"Dalimi A.","year":"2012","journal-title":"Iran J Parasitol"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540500305894"},{"key":"e_1_2_7_22_1","volume-title":"Principals and practice of infectious diseases","author":"Mandell G. 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