{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:34:02Z","timestamp":1778747642309,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noscapine, an opium alkaloid, was discovered to bind tubulin, arrest dividing cells at mitosis, and selectively induce apoptosis to cancer cells. N\u20103\u2010Br\u2010Benzyl\u2010Noscapine (Br\u2010Bn\u2010Nos), one of the derivatives of noscapine, was demonstrated to have improved anticancer potential compared with noscapine. We approached to evaluate the single and combined effect of Br\u2010Bn\u2010Nos and docetaxel (DOX) based on molecular modeling and cellular study. The individual predicted free energy of binding (\u2206<jats:italic>G<\/jats:italic><jats:sub>bind,pred<\/jats:sub>) for Br\u2010Bn\u2010Nos and DOX with tubulin was found to be \u221228.89 and \u221236.07\u00a0kcal\/mol based on molecular mechanics generalized Born solvation area (MM\u2010GBSA) as well as \u221226.21 and \u221234.65\u00a0kcal\/mol based on molecular mechanics Poisson Boltzmann solvation area (MM\u2010PBSA), respectively. However, the \u2206G<jats:sub>bind,pred<\/jats:sub> of Br\u2010Bn\u2010Nos was significantly reduced (\u221233.02 and \u221230.24\u00a0kcal\/mol using MM\u2010GBSA and MM\u2010PBSA) in the presence of DOX on its binding pocket. Parenthetically, the \u2206<jats:italic>G<\/jats:italic><jats:sub>bind,pred<\/jats:sub> of DOX was significantly reduced (\u221237.17 and \u221232.80\u00a0kcal\/mol using MM\u2010GBSA and MM\u2010PBSA) in the presence of Br\u2010Bn\u2010Nos on its binding pocket. The reduced \u2206<jats:italic>G<\/jats:italic><jats:sub>bind,pred<\/jats:sub> in the presence of Br\u2010Bn\u2010Nos and DOX together indicated a combination effect of both the ligands. The combined interaction of both the agents onto tubulin dimmer was also determined experimentally using purified tubulin, in which a\u00a0combination regimen of Br\u2010Bn\u2010Nos and DOX reduced the fluorescence intensity of tubulin to a higher value (68%) compared with the single regimen. Further, isobologram analysis revealed the synergistic effect of Br\u2010Bn\u2010Nos and DOX in antiproliferative activity using MCF\u20107 cell line at 48\u00a0hr (sum FIC\u00a0=\u00a00.49) and at 72\u00a0hr (sum FIC\u00a0=\u00a00.62). The combination dose regimen of Br\u2010Bn\u2010Nos and DOX blocks the cell cycle progression at the G2\/M phase and induces apoptosis to cancer cells more effectively compared with the single regimen. Taken together, our study provides compelling evidence that the anticancer potential of noscapine derivatives may be substantially improved when it is used in a combined application with DOX for breast cancer.<\/jats:p>","DOI":"10.1111\/cbdd.13902","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T17:28:38Z","timestamp":1623259718000},"page":"466-479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synergistic interaction of N\u20103\u2010Br\u2010benzyl\u2010noscapine and docetaxel abrogates oncogenic potential of breast cancer cells"],"prefix":"10.1111","volume":"98","author":[{"given":"Shruti Gamya","family":"Dash","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Bioinformatics Centre of Excellence in Natural Products and Therapeutics Sambalpur University Sambalpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas","family":"Kantevari","sequence":"additional","affiliation":[{"name":"Fluoro and Agrochemicals Division CSIR\u2010Indian Institute of Chemical Technology Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swaroop Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Bencos Research Solutions Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep Kumar","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics Centre of Excellence in Natural Products and Therapeutics Sambalpur University Sambalpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464304"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00523a008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb200099u"},{"key":"e_1_2_8_6_1","volume-title":"AMBER. 2016","author":"Case D. 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