دورية أكاديمية
أعرض في EDS

Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.

التفاصيل البيبلوغرافية
العنوان: Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.
المؤلفون: Denison M; Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, Michigan 48202, United States., Garcia SP; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States., Ullrich A; Department of Oncology, Wayne State University, Detroit, Michigan 48201, United States., Podgorski I; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan 48201, United States.; Karmanos Cancer Institute, Detroit, Michigan 48201, United States., Gibson H; Department of Oncology, Wayne State University, Detroit, Michigan 48201, United States.; Karmanos Cancer Institute, Detroit, Michigan 48201, United States., Turro C; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States., Kodanko JJ; Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, Michigan 48202, United States.; Karmanos Cancer Institute, Detroit, Michigan 48201, United States.
المصدر: Inorganic chemistry [Inorg Chem] 2024 Apr 29; Vol. 63 (17), pp. 7973-7983. Date of Electronic Publication: 2024 Apr 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0366543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-510X (Electronic) Linking ISSN: 00201669 NLM ISO Abbreviation: Inorg Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Easton, Pa.] American Chemical Society.
مواضيع طبية MeSH: Cathepsins*/antagonists & inhibitors , Cathepsins*/metabolism , Green Light* , Photochemotherapy* , Photosensitizing Agents*/pharmacology , Photosensitizing Agents*/chemistry , Photosensitizing Agents*/chemical synthesis , Ruthenium*/chemistry , Ruthenium*/pharmacology, Animals ; Humans ; Mice ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/chemical synthesis ; Cell Line, Tumor ; Cell Survival/drug effects ; Coordination Complexes/pharmacology ; Coordination Complexes/chemistry ; Coordination Complexes/chemical synthesis ; Molecular Structure
مستخلص: Dysregulated cathepsin activity is linked to various human diseases including metabolic disorders, autoimmune conditions, and cancer. Given the overexpression of cathepsin in the tumor microenvironment, cathepsin inhibitors are promising pharmacological agents and drug delivery vehicles for cancer treatment. In this study, we describe the synthesis and photochemical and biological assessment of a dual-action agent based on ruthenium that is conjugated with a cathepsin inhibitor, designed for both photodynamic therapy (PDT) and photochemotherapy (PCT). The ruthenium-cathepsin inhibitor conjugate was synthesized through an oxime click reaction, combining a pan-cathepsin inhibitor based on E64d with the Ru(II) PCT/PDT fragment [Ru(dqpy)(dppn)], where dqpy = 2,6-di(quinoline-2-yl)pyridine and dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine. Photochemical investigations validated the conjugate's ability to release a triazole-containing cathepsin inhibitor for PCT and to generate singlet oxygen for PDT upon exposure to green light. Inhibition studies demonstrated the conjugate's potent and irreversible inactivation of purified and intracellular cysteine cathepsins. Two Ru(II) PCT/PDT agents based on the [Ru(dqpy)(dppn)] moiety were evaluated for photoinduced cytotoxicity in 4T1 murine triple-negative breast cancer cells, L929 fibroblasts, and M0, M1, and M2 macrophages. The cathepsin inhibitor conjugate displayed notable selectivity for inducing cell death under irradiation compared to dark conditions, mitigating toxicity in the dark observed with the triazole control complex [Ru(dqpy)(dppn)(MeTz)] 2+ (MeTz = 1-methyl-1 H -1,2,4-triazole). Notably, our lead complex is among a limited number of dual PCT/PDT agents activated with green light.
References: J Enzyme Inhib Med Chem. 2022 Dec;37(1):2566-2573. (PMID: 36120947)
Bioconjug Chem. 2016 May 18;27(5):1267-75. (PMID: 27070848)
J Med Chem. 2006 Aug 24;49(17):5262-72. (PMID: 16913715)
Chembiochem. 2023 Feb 14;24(4):e202200647. (PMID: 36479913)
J Phys Chem A. 2014 Nov 13;118(45):10603-10. (PMID: 25027458)
Chem Commun (Camb). 2022 Aug 11;58(65):9100-9103. (PMID: 35880482)
Int J Mol Sci. 2017 Dec 29;19(1):. (PMID: 29286292)
Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6752-6. (PMID: 24844571)
Lasers Med Sci. 2017 Nov;32(8):1909-1918. (PMID: 28900751)
J Med Chem. 2023 Feb 23;66(4):3088-3105. (PMID: 36752718)
Genes Dev. 2006 Mar 1;20(5):543-56. (PMID: 16481467)
Biochimie. 2010 Nov;92(11):1618-24. (PMID: 20447439)
Chemistry. 2022 Apr 27;28(24):e202104430. (PMID: 35235227)
Biomaterials. 2021 Aug;275:120915. (PMID: 34102525)
Bioconjug Chem. 2002 Jul-Aug;13(4):855-69. (PMID: 12121142)
Mol Cancer. 2014 Mar 02;13:43. (PMID: 24580730)
J Pharmacobiodyn. 1986 Aug;9(8):672-7. (PMID: 3023601)
J Am Chem Soc. 2018 Oct 31;140(43):14367-14380. (PMID: 30278123)
Chem Sci. 2018 Jul 20;9(32):6711-6720. (PMID: 30310605)
Chemistry. 2012 Jul 9;18(28):8617-21. (PMID: 22700010)
Chem Commun (Camb). 2015 May 25;51(42):8777-80. (PMID: 25912170)
Front Immunol. 2021 May 07;12:642285. (PMID: 34025653)
Pharmacol Ther. 2015 Nov;155:105-16. (PMID: 26299995)
Dalton Trans. 2018 Aug 21;47(31):10330-10343. (PMID: 29978870)
Cancers (Basel). 2020 Sep 10;12(9):. (PMID: 32927704)
ACS Chem Biol. 2015 Sep 18;10(9):1977-88. (PMID: 26039341)
Cells. 2020 Jul 13;9(7):. (PMID: 32668602)
Biochemistry. 2022 Feb 15;61(4):228-238. (PMID: 35119840)
ChemTexts. 2022;8(2):12. (PMID: 35287314)
Bioorg Med Chem. 2019 Jun 15;27(12):2666-2675. (PMID: 31103403)
Photochem Photobiol Sci. 2015 Nov;14(11):2014-23. (PMID: 25666432)
EJNMMI Res. 2020 Sep 29;10(1):111. (PMID: 32990883)
J Am Chem Soc. 2014 Dec 10;136(49):17095-101. (PMID: 25393595)
Biol Chem. 2002 May;383(5):839-42. (PMID: 12108549)
Dalton Trans. 2009 Dec 28;(48):10690-701. (PMID: 20023896)
Nat Rev Cancer. 2006 Oct;6(10):764-75. (PMID: 16990854)
Expert Opin Ther Targets. 2013 Mar;17(3):281-91. (PMID: 23293836)
Chem Rev. 2017 Aug 9;117(15):10358-10376. (PMID: 28640998)
Exp Cell Res. 2003 Feb 15;283(2):206-14. (PMID: 12581740)
Genes Dev. 2013 Oct 1;27(19):2086-98. (PMID: 24065739)
Photodermatol Photoimmunol Photomed. 1997 Oct-Dec;13(5-6):181-5. (PMID: 9542754)
Angew Chem Int Ed Engl. 2017 Sep 11;56(38):11549-11553. (PMID: 28666065)
Bioconjug Chem. 2008 Dec;19(12):2543-8. (PMID: 19053314)
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2497-502. (PMID: 20133781)
Front Immunol. 2019 Aug 28;10:2037. (PMID: 31555270)
Genes Dev. 2011 Dec 1;25(23):2465-79. (PMID: 22156207)
Inorg Chem. 2021 Dec 20;60(24):18964-18974. (PMID: 34846875)
Chem Commun (Camb). 2010 Apr 14;46(14):2426-8. (PMID: 20379547)
Angew Chem Int Ed Engl. 2023 Jun 12;62(24):e202218768. (PMID: 36890113)
Photochem Photobiol. 2022 Mar;98(2):378-388. (PMID: 34866185)
J Cell Physiol. 2018 Sep;233(9):6425-6440. (PMID: 29319160)
Chem Sci. 2022 Apr 1;13(18):5085-5106. (PMID: 35655575)
Biol Chem. 2002 Jul-Aug;383(7-8):1305-8. (PMID: 12437121)
Cancer Res. 2007 Aug 1;67(15):7378-85. (PMID: 17671208)
Cancer Res. 2012 Mar 1;72(5):1199-209. (PMID: 22266111)
Int J Mol Sci. 2019 Jul 23;20(14):. (PMID: 31340550)
Chem Rev. 2019 Jan 23;119(2):797-828. (PMID: 30295467)
Biochim Biophys Acta. 2014 Aug;1840(8):2560-70. (PMID: 24680817)
Chem Biodivers. 2019 Jan;16(1):e1800520. (PMID: 30566287)
J Biol Inorg Chem. 2021 Sep;26(6):667-674. (PMID: 34378103)
Oncogene. 2008 Jul 10;27(30):4191-9. (PMID: 18345026)
Exp Cell Res. 2019 Sep 15;382(2):111472. (PMID: 31229505)
Oncogene. 2015 Dec 10;34(50):6066-78. (PMID: 25798843)
Biochimie. 2008 Feb;90(2):194-207. (PMID: 17825974)
CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
Chimia (Aarau). 2021 Oct 27;75(10):845-855. (PMID: 34728011)
Oncotarget. 2019 Sep 17;10(53):5560-5568. (PMID: 31565189)
Chemistry. 2014 Jan 3;20(1):34-41. (PMID: 24302514)
J Am Chem Soc. 2023 Jul 12;145(27):14963-14980. (PMID: 37379365)
Photochem Photobiol Sci. 2016 Apr;15(4):481-95. (PMID: 26947517)
Chem Sci. 2021 Aug 3;12(35):11810-11820. (PMID: 34659720)
J Am Chem Soc. 2023 Nov 1;145(43):23397-23415. (PMID: 37846939)
Trends Cell Biol. 2011 Apr;21(4):228-37. (PMID: 21232958)
Clin Cancer Res. 2022 Sep 1;28(17):3729-3741. (PMID: 35792882)
Neoplasia. 2013 Oct;15(10):1125-37. (PMID: 24204192)
Mol Cancer. 2010 Aug 04;9:207. (PMID: 20684763)
J Am Chem Soc. 2020 Mar 11;142(10):4639-4647. (PMID: 32065521)
Chem Commun (Camb). 2017 Jun 20;53(50):6768-6771. (PMID: 28597879)
Arch Biochem Biophys. 1992 Dec;299(2):377-80. (PMID: 1444478)
معلومات مُعتمدة: R01 GM098285 United States GM NIGMS NIH HHS; S10 OD028488 United States OD NIH HHS; T32 GM142519 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (Antineoplastic Agents)
EC 3.4.- (Cathepsins)
0 (Coordination Complexes)
0 (Photosensitizing Agents)
7UI0TKC3U5 (Ruthenium)
تواريخ الأحداث: Date Created: 20240415 Date Completed: 20240429 Latest Revision: 20240731
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC11066580
DOI: 10.1021/acs.inorgchem.4c01008
PMID: 38616353
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-510X
DOI:10.1021/acs.inorgchem.4c01008