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However, no such MMP\u20102 inhibitor has come out in the market to date for treating leukemia. In this study, synthesis, biological evaluation, and molecular modeling studies of a set of biphenylsulfonamide derivatives as promising MMP\u20102 inhibitors were performed, focusing on their potential applications as antileukemic therapeutics. Compounds DH\u201018 and DH\u201019 exerted the most effective MMP\u20102 inhibition (IC<jats:sub>50<\/jats:sub> of 139.45\u2009nM and 115.16\u2009nM, respectively) with potent antileukemic efficacy against the CML cell line K562 (IC<jats:sub>50<\/jats:sub> of 0.338\u2009\u00b5M and 0.398\u2009\u00b5M, respectively). The lead molecules DH\u201018 and DH\u201019 reduced the MMP\u20102 expression by 21.3% and 17.8%, respectively with effective apoptotic induction (45.4% and 39.8%, respectively) in the K562 cell line. Moreover, both these compounds significantly arrested different phases of the cell cycle. Again, both these molecules depicted promising antiangiogenic efficacy in the ACHN cell line. Nevertheless, the molecular docking and molecular dynamics (MD) simulation studies revealed that DH\u201018 formed strong bidentate chelation with the catalytic Zn<jats:sup>2+<\/jats:sup> ion through the hydroxamate zinc binding group (ZBG). Apart from that, the MD simulation study also disclosed stable binding interactions of DH\u201018 and MMP\u20102 along with crucial interactions with active site amino acid residues namely His120, Glu121, His124, His130, Pro140, and Tyr142. In a nutshell, this study highlighted the importance of biphenylsulfonamide\u2010based novel and promising MMP\u20102 inhibitors to open up a new avenue for potential therapy against CML.<\/jats:p>","DOI":"10.1002\/ddr.22255","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T01:05:47Z","timestamp":1725498347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biphenylsulfonamides as effective MMP\u20102 inhibitors with promising antileukemic efficacy: Synthesis, in vitro biological evaluation, molecular docking, and MD simulation analysis"],"prefix":"10.1002","volume":"85","author":[{"given":"Sandip K.","family":"Baidya","sequence":"first","affiliation":[{"name":"Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology Natural Science Laboratory Jadavpur University Kolkata India"},{"name":"School of Pharmacy Sister Nivedita University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarun","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Epigenetic Research Laboratory Birla Institute of Technology and Science\u2010Pilani Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambati","family":"Himaja","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Epigenetic Research Laboratory Birla Institute of Technology and Science\u2010Pilani Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvankar","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology Natural Science Laboratory Jadavpur University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjib","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology Natural Science Laboratory Jadavpur University Kolkata India"},{"name":"School of Pharmacy Sister Nivedita University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaram","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Epigenetic Research Laboratory Birla Institute of Technology and Science\u2010Pilani Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-738X","authenticated-orcid":false,"given":"Tarun","family":"Jha","sequence":"additional","affiliation":[{"name":"Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology Natural Science Laboratory Jadavpur University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-7716","authenticated-orcid":false,"given":"Nilanjan","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology Natural Science Laboratory Jadavpur University Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201701330"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2017.12.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.07.023"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201300086"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.05.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245330310001621323"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jmi.12133"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.113044"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01855"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2248509"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.01.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2013.01.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5556"},{"issue":"1","key":"e_1_2_8_15_1","first-page":"59","article-title":"The prognostic value of CXCR4, MMP\u20102 and MMP\u20109 in tongue squamous carcinoma","volume":"60","author":"Ciuc\u0103 F. 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