دورية أكاديمية
Design, Synthesis, and Biological Evaluation of Pyrimidine Dihydroquinoxalinone Derivatives as Tubulin Colchicine Site-Binding Agents That Displayed Potent Anticancer Activity Both In Vitro and In Vivo.
العنوان: | Design, Synthesis, and Biological Evaluation of Pyrimidine Dihydroquinoxalinone Derivatives as Tubulin Colchicine Site-Binding Agents That Displayed Potent Anticancer Activity Both In Vitro and In Vivo. |
---|---|
المؤلفون: | Pochampally S; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Hartman KL; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Wang R; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Wang J; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Yun MK; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States., Parmar K; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Park H; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Meibohm B; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., White SW; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States., Li W; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States., Miller DD; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States. |
المصدر: | ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2023 Mar 22; Vol. 6 (4), pp. 526-545. Date of Electronic Publication: 2023 Mar 22 (Print Publication: 2023). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101721411 Publication Model: eCollection Cited Medium: Internet ISSN: 2575-9108 (Electronic) Linking ISSN: 25759108 NLM ISO Abbreviation: ACS Pharmacol Transl Sci Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, [2018]- |
مستخلص: | Polymerization of tubulin dimers to form microtubules is one of the key events in cell proliferation. The inhibition of this event has long been recognized as a potential treatment option for various types of cancer. Compound 1e was previously developed by our team as a potent inhibitor of tubulin polymerization that binds to the colchicine site. To further improve the potency and therapeutic properties of compound 1e , we hypothesized based on the X-ray crystal structure that modification of the pyrimidine dihydroquinoxalinone scaffold with additional hetero-atom (N, O, and S) substituents could allow the resulting new compounds to bind more tightly to the colchicine site and display greater efficacy in cancer therapy. We therefore synthesized a series of new pyrimidine dihydroquinoxalinone derivatives, compounds 10 , 12b-c , 12e , 12h , and 12j-l , and evaluated their cytotoxicity and relative ability to inhibit proliferation, resulting in the discovery of new tubulin-polymerization inhibitors. Among these, the most potent new inhibitor was compound 12k , which exhibited high cytotoxic activity in vitro, a longer half-life than the parental compound in liver microsomes (IC Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.) |
References: | Methods Mol Med. 2007;137:235-43. (PMID: 18085233) Nat Rev Cancer. 2005 Jun;5(6):423-35. (PMID: 15928673) Nat Rev Mol Cell Biol. 2015 Dec;16(12):711-26. (PMID: 26562752) Mol Pharmacol. 2019 Dec;96(6):711-719. (PMID: 31585985) J Biol Chem. 2014 Jan 17;289(3):1852-65. (PMID: 24297176) Drug Deliv Transl Res. 2015 Jun;5(3):199-208. (PMID: 25924699) Nat Rev Drug Discov. 2010 Oct;9(10):790-803. (PMID: 20885410) Eur J Med Chem. 2014 Oct 6;85:391-8. (PMID: 25108078) Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14. (PMID: 23793146) Science. 2013 Feb 1;339(6119):587-90. (PMID: 23287720) Nat Rev Cancer. 2004 Apr;4(4):253-65. (PMID: 15057285) ACS Med Chem Lett. 2014 Feb 27;5(5):480-4. (PMID: 24900865) Br J Cancer. 2010 Jan 19;102(2):316-24. (PMID: 20029418) Anticancer Res. 2003 Mar-Apr;23(2B):1433-40. (PMID: 12820406) Drug Metab Dispos. 2001 Jul;29(7):1057-67. (PMID: 11408374) Cancer Res. 2007 Jun 15;67(12):5865-71. (PMID: 17575155) J Med Chem. 2016 Oct 13;59(19):8685-8711. (PMID: 27348355) ChemMedChem. 2014 Apr;9(4):847-54. (PMID: 24678059) Curr Med Chem. 2015;22(11):1348-60. (PMID: 25620094) Mol Cancer Ther. 2020 Feb;19(2):348-363. (PMID: 31645441) Clin Cancer Res. 2011 Aug 1;17(15):5152-60. (PMID: 21690571) J Med Chem. 2014 Sep 11;57(17):7355-66. (PMID: 25122533) J Med Chem. 2021 Sep 9;64(17):13072-13095. (PMID: 34406768) J Med Chem. 2018 Feb 22;61(4):1704-1718. (PMID: 29406710) Biol Proced Online. 2010 Apr 08;12(1):113-7. (PMID: 21406120) Cancer Res. 2002 Dec 15;62(24):7247-53. (PMID: 12499266) J Biol Chem. 2019 May 17;294(20):8161-8170. (PMID: 30940730) ACS Chem Biol. 2019 Dec 20;14(12):2810-2821. (PMID: 31714738) J Med Chem. 2021 Aug 26;64(16):12049-12074. (PMID: 34378386) J Mol Biol. 2011 Sep 9;412(1):35-42. (PMID: 21787788) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) J Biol Chem. 2009 Jun 19;284(25):17039-17051. (PMID: 19339240) Expert Opin Investig Drugs. 2009 Feb;18(2):189-97. (PMID: 19236265) Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67. (PMID: 22505256) Bioorg Med Chem. 1996 Oct;4(10):1659-71. (PMID: 8931935) Org Biomol Chem. 2015 Nov 21;13(43):10620-30. (PMID: 26340222) Br J Pharmacol. 2013 Feb;168(3):673-85. (PMID: 23004938) J Clin Pharmacol. 2016 Aug;56(8):966-73. (PMID: 26632033) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692) J Med Chem. 2005 Jan 27;48(2):457-65. (PMID: 15658859) Cell Motil Cytoskeleton. 1999;43(1):63-71. (PMID: 10340704) Eur J Med Chem. 2015 Mar 6;92:246-56. (PMID: 25559205) J Biol Chem. 1996 Jun 21;271(25):14707-11. (PMID: 8663038) Nat Commun. 2017 Jun 06;8:15787. (PMID: 28585532) Mol Cancer Ther. 2010 Dec;9(12):3410-9. (PMID: 21159616) Future Oncol. 2010 Aug;6(8):1219-28. (PMID: 20799867) Pharm Res. 2012 Nov;29(11):3064-74. (PMID: 23054088) J Med Chem. 2014 Feb 27;57(4):1390-402. (PMID: 24502232) Biochemistry. 2001 Oct 9;40(40):11975-84. (PMID: 11580273) J Org Chem. 2017 Mar 17;82(6):3152-3158. (PMID: 28233495) J Med Chem. 2017 Jul 13;60(13):5586-5598. (PMID: 28653846) Drug Discov Today. 2022 Mar;27(3):759-776. (PMID: 34890803) |
معلومات مُعتمدة: | R01 CA193609 United States CA NCI NIH HHS; R01 CA240447 United States CA NCI NIH HHS; R01 CA148706 United States CA NCI NIH HHS; S10 OD010678 United States OD NIH HHS; S10 RR026377 United States RR NCRR NIH HHS |
تواريخ الأحداث: | Date Created: 20230421 Latest Revision: 20240323 |
رمز التحديث: | 20240323 |
مُعرف محوري في PubMed: | PMC10111625 |
DOI: | 10.1021/acsptsci.2c00108 |
PMID: | 37082747 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2575-9108 |
---|---|
DOI: | 10.1021/acsptsci.2c00108 |