{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:03:54Z","timestamp":1772820234961,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"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":[[2014,7]]},"abstract":"The CRK<\/jats:styled-content>3 cyclin\u2010dependent kinase of Leishmania<\/jats:italic> plays an important role in regulating the cell\u2010cycle progression at the G2\/M phase checkpoint transition, proliferation, and viability inside the host macrophage. In this study, a novel fragment\u2010based QSAR<\/jats:styled-content> model has been developed using 22 pyrazole\u2010derived compounds exhibiting inhibitory activity against Leishmanial <\/jats:italic>CRK<\/jats:styled-content>3. Unlike other QSAR<\/jats:styled-content> methods, this fragment\u2010based method gives flexibility to study the relationship between molecular fragments of interest and their contribution for the variation in the biological response by evaluating cross\u2010term fragment descriptors. Based on the fragment\u2010based QSAR<\/jats:styled-content> model, a combinatorial library was generated, and top two compounds were reported after predicting their activity. The QSAR<\/jats:styled-content> model showed satisfactory statistical parameters for the data set (r<\/jats:italic>2<\/jats:sup>\u00a0=\u00a00.8752, q<\/jats:italic>2<\/jats:sup>\u00a0=\u00a00.6690, F<\/jats:italic>\u2010ratio\u00a0=\u00a030.37, and pred_r<\/jats:italic>2<\/jats:sup>\u00a0=\u00a00.8632) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron\u2010rich substitution at R<\/jats:styled-content>1<\/jats:sub> position improves the inhibitory activity, while decline in inhibitory activity was observed in presence of nitrogen at R<\/jats:styled-content>2<\/jats:sub> position. The analysis carried out in this study provides a substantial basis for consideration of the designed pyrazole\u2010based leads as potent antileishmanial drugs.<\/jats:p>","DOI":"10.1111\/cbdd.12290","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T12:19:07Z","timestamp":1390393147000},"page":"54-62","source":"Crossref","is-referenced-by-count":22,"title":["Novel Fragment\u2010Based QSAR<\/scp> Modeling and Combinatorial Design of Pyrazole\u2010Derived CRK<\/scp>3 Inhibitors as Potent Antileishmanials"],"prefix":"10.1111","volume":"84","author":[{"given":"Sukriti","family":"Goyal","sequence":"first","affiliation":[{"name":"Apaji Institute of Mathematics & Applied Computer Technology Banasthali University Tonk 304022 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaspreet K.","family":"Dhanjal","sequence":"additional","affiliation":[{"name":"School of Biotechnology Jawaharlal Nehru University New Delhi 110067 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chetna","family":"Tyagi","sequence":"additional","affiliation":[{"name":"School of Biotechnology Jawaharlal Nehru University New Delhi 110067 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manisha","family":"Goyal","sequence":"additional","affiliation":[{"name":"Apaji Institute of Mathematics & Applied Computer Technology Banasthali University Tonk 304022 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhinav","family":"Grover","sequence":"additional","affiliation":[{"name":"School of Biotechnology Jawaharlal Nehru University New Delhi 110067 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-011-1187-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/00034983.1984.11811768","article-title":"Inhibition of Leishmania amastigote growth by antipain and leupeptin","volume":"78","author":"Coombs G.H.","year":"1984","journal-title":"Ann Trop Med Parasitol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001475"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules14072317"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00014-08"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011882"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2007.00523.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340612801216247"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(87)90476-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.1.1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2005.08.018"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10153"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3033-3042.2004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm960666x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.t01-2-00527.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5376.533"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204503"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201100344"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756360903524296"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802608786786552"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1023\/A:1021372108686","article-title":"Predictive QSAR modeling based on diversity sampling of experimental datasets for the training and test set selection","volume":"5","author":"Golbraikh A.","year":"2002","journal-title":"Mol Divers"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2008.05.028"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1093-3263(01)00123-1"},{"key":"e_1_2_8_25_1","first-page":"3","article-title":"Expeditious synthesis, antibacterial activity evaluation and GQSAR studies of 3\u2010bisoxindoles, 2\u2010oxindolyl\u20102\u2010hydroxyindan\u20101,3\u2010diones and 2\u2010oxindolyl\u20102\u2010hydroxyacenaphthylen\u20101\u2010ones","volume":"2013","author":"Lakshmi N.V.","year":"2013","journal-title":"R SocChem"}],"container-title":["Chemical Biology & Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcbdd.12290","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.12290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T23:07:27Z","timestamp":1696288047000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.12290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,14]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1111\/cbdd.12290"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.12290","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,14]]}}}