1 Ocak 2023 Dergi makalesi Açık Erişim

Wijesinghe, Tharushi P.; Kaya, Busra; Gonzalvez, Miguel A.; Harmer, Jeffrey R.; Gholam Azad, Mahan; Bernhardt, Paul V.; Dharmasivam, Mahendiran; Richardson, Des R.

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/271194</identifier>
  <creators>
    <creator>
      <creatorName>Wijesinghe, Tharushi P.</creatorName>
      <givenName>Tharushi P.</givenName>
      <familyName>Wijesinghe</familyName>
      <affiliation>Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol &amp; Drug Discovery, Brisbane, Qld 4111, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Kaya, Busra</creatorName>
      <givenName>Busra</givenName>
      <familyName>Kaya</familyName>
      <affiliation>Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol &amp; Drug Discovery, Brisbane, Qld 4111, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Gonzalvez, Miguel A.</creatorName>
      <givenName>Miguel A.</givenName>
      <familyName>Gonzalvez</familyName>
      <affiliation>Univ Queensland, Sch Chem &amp; Mol Biosci, Brisbane, Qld 4072, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Harmer, Jeffrey R.</creatorName>
      <givenName>Jeffrey R.</givenName>
      <familyName>Harmer</familyName>
      <affiliation>Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Gholam Azad, Mahan</creatorName>
      <givenName>Mahan</givenName>
      <familyName>Gholam Azad</familyName>
      <affiliation>Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol &amp; Drug Discovery, Brisbane, Qld 4111, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Bernhardt, Paul V.</creatorName>
      <givenName>Paul V.</givenName>
      <familyName>Bernhardt</familyName>
      <affiliation>Univ Queensland, Sch Chem &amp; Mol Biosci, Brisbane, Qld 4072, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Dharmasivam, Mahendiran</creatorName>
      <givenName>Mahendiran</givenName>
      <familyName>Dharmasivam</familyName>
      <affiliation>Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol &amp; Drug Discovery, Brisbane, Qld 4111, Australia</affiliation>
    </creator>
    <creator>
      <creatorName>Richardson, Des R.</creatorName>
      <givenName>Des R.</givenName>
      <familyName>Richardson</familyName>
    </creator>
  </creators>
  <titles>
    <title>Steric Blockade Of Oxy-Myoglobin Oxidation By Thiosemicarbazones: Structure-Activity Relationships Of The Novel Ppp4Pt Series</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2023</publicationYear>
  <dates>
    <date dateType="Issued">2023-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/271194</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1021/acs.jmedchem.3c01612</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;The di-2-pyridylketone thiosemicarbazones demonstrated marked anticancer efficacy, prompting progression of DpC to clinical trials. However, DpC induced deleterious oxy-myoglobin oxidation, stifling development. To address this, novel substituted phenyl thiosemicarbazone (PPP4pT) analogues and their Fe-(III), Cu-(II), and Zn-(II) complexes were prepared. The PPP4pT analogues demonstrated potent antiproliferative activity (IC50: 0.009-0.066 mu M), with the 1:1 Cu:L complexes showing the greatest efficacy. Substitutions leading to decreased redox potential of the PPP4pT:Cu-(II) complexes were associated with higher antiproliferative activity, while increasing potential correlated with increased redox activity. Surprisingly, there was no correlation between redox activity and antiproliferative efficacy. The PPP4pT:Fe-(III) complexes attenuated oxy-myoglobin oxidation significantly more than the clinically trialed thiosemicarbazones, Triapine, COTI-2, and DpC, or earlier thiosemicarbazone series. Incorporation of phenyl- and styryl-substituents led to steric blockade, preventing approach of the PPP4pT:Fe-(III) complexes to the heme plane and its oxidation. The 1:1 Cu-(II):PPP4pT complexes were inert to transmetalation and did not induce oxy-myoglobin oxidation.&lt;/p&gt;</description>
  </descriptions>
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