Phthalocyanine−Polyamine Conjugates as Highly Efficient Photosensitizers for Photodynamic Therapy
A series of silicon(IV) phthalocyanines substituted axially with different polyamine moieties have been prepared. Their fluorescence quantum yields (ΦF = 0.03−0.08) in N,N-dimethylformamide are low because of reductive quenching by the amino moieties. The values are significantly increased in aqueou...
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| Veröffentlicht in: | Journal of medicinal chemistry 2011-01, Vol.54 (1), p.320-330 |
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| creator | Jiang, Xiong-Jie Yeung, Sin-Lui Lo, Pui-Chi Fong, Wing-Ping Ng, Dennis K. P |
| description | A series of silicon(IV) phthalocyanines substituted axially with different polyamine moieties have been prepared. Their fluorescence quantum yields (ΦF = 0.03−0.08) in N,N-dimethylformamide are low because of reductive quenching by the amino moieties. The values are significantly increased in aqueous media (ΦF = 0.12−0.21) as a result of protonation of the amino substituents. All the compounds are highly photocytotoxic against human colon adenocarcinoma HT29 cells and Chinese hamster ovary cells with IC50 values as low as 1.1 nM. Flow cytometric studies of two selected compounds (2 and 5) against HT29 cells have shown that they induce apoptosis extensively. As shown by confocal microscopy, these two compounds also show high affinity toward the lysosomes, but not the mitochondria, of the cells. Their in vivo photodynamic activity has also been investigated using HT29 tumor bearing nude mice. Both of them can effectively inhibit the growth of the tumor without causing apparent injury to the liver of the mice. |
| doi_str_mv | 10.1021/jm101253v |
| format | Article |
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P</creator><creatorcontrib>Jiang, Xiong-Jie ; Yeung, Sin-Lui ; Lo, Pui-Chi ; Fong, Wing-Ping ; Ng, Dennis K. P</creatorcontrib><description>A series of silicon(IV) phthalocyanines substituted axially with different polyamine moieties have been prepared. Their fluorescence quantum yields (ΦF = 0.03−0.08) in N,N-dimethylformamide are low because of reductive quenching by the amino moieties. The values are significantly increased in aqueous media (ΦF = 0.12−0.21) as a result of protonation of the amino substituents. All the compounds are highly photocytotoxic against human colon adenocarcinoma HT29 cells and Chinese hamster ovary cells with IC50 values as low as 1.1 nM. Flow cytometric studies of two selected compounds (2 and 5) against HT29 cells have shown that they induce apoptosis extensively. As shown by confocal microscopy, these two compounds also show high affinity toward the lysosomes, but not the mitochondria, of the cells. Their in vivo photodynamic activity has also been investigated using HT29 tumor bearing nude mice. Both of them can effectively inhibit the growth of the tumor without causing apparent injury to the liver of the mice.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm101253v</identifier><identifier>PMID: 21138268</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Apoptosis - drug effects ; CHO Cells ; Cricetinae ; Cricetulus ; Drug Screening Assays, Antitumor ; HT29 Cells ; Humans ; Indoles - chemical synthesis ; Indoles - chemistry ; Indoles - pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Photochemotherapy ; Photosensitizing Agents - chemical synthesis ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - pharmacology ; Polyamines - chemical synthesis ; Polyamines - chemistry ; Polyamines - pharmacology ; Structure-Activity Relationship ; Transplantation, Heterologous</subject><ispartof>Journal of medicinal chemistry, 2011-01, Vol.54 (1), p.320-330</ispartof><rights>Copyright © 2010 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a380t-f7a7e08729474d97a547d81e6808ac2d6d50728bb14b581bca7295da719605a73</citedby><cites>FETCH-LOGICAL-a380t-f7a7e08729474d97a547d81e6808ac2d6d50728bb14b581bca7295da719605a73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm101253v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm101253v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21138268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Xiong-Jie</creatorcontrib><creatorcontrib>Yeung, Sin-Lui</creatorcontrib><creatorcontrib>Lo, Pui-Chi</creatorcontrib><creatorcontrib>Fong, Wing-Ping</creatorcontrib><creatorcontrib>Ng, Dennis K. P</creatorcontrib><title>Phthalocyanine−Polyamine Conjugates as Highly Efficient Photosensitizers for Photodynamic Therapy</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A series of silicon(IV) phthalocyanines substituted axially with different polyamine moieties have been prepared. Their fluorescence quantum yields (ΦF = 0.03−0.08) in N,N-dimethylformamide are low because of reductive quenching by the amino moieties. The values are significantly increased in aqueous media (ΦF = 0.12−0.21) as a result of protonation of the amino substituents. All the compounds are highly photocytotoxic against human colon adenocarcinoma HT29 cells and Chinese hamster ovary cells with IC50 values as low as 1.1 nM. Flow cytometric studies of two selected compounds (2 and 5) against HT29 cells have shown that they induce apoptosis extensively. As shown by confocal microscopy, these two compounds also show high affinity toward the lysosomes, but not the mitochondria, of the cells. Their in vivo photodynamic activity has also been investigated using HT29 tumor bearing nude mice. Both of them can effectively inhibit the growth of the tumor without causing apparent injury to the liver of the mice.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Drug Screening Assays, Antitumor</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - chemistry</subject><subject>Indoles - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Photochemotherapy</subject><subject>Photosensitizing Agents - chemical synthesis</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Polyamines - chemical synthesis</subject><subject>Polyamines - chemistry</subject><subject>Polyamines - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Transplantation, Heterologous</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM1Kw0AQgBdRbK0efAHJRcRDdHbzs5ujlGqFgj3Uc5hsNk1Ckq27iRCfwLOP6JMYSe3J0wzDxwfzEXJJ4Y4Co_dlTYGywHs_IlMaMHB9Af4xmQIw5rKQeRNyZm0JAB5l3imZMEo9wUIxJXKdtzlWWvbYFI36_vxa66rHetiduW7Kboutsg5aZ1ls86p3FllWyEI1rbPOdautamzRFh_KWCfTZjymfTMYpLPJlcFdf05OMqysutjPGXl9XGzmS3f18vQ8f1i56Alo3YwjVyA4i3zupxHHwOepoCoUIFCyNEwD4EwkCfWTQNBE4oAGKXIahRAg92bkZvTujH7rlG3jurBSVRU2Snc2FhGE3PfBG8jbkZRGW2tUFu9MUaPpYwrxb9L4kHRgr_bWLqlVeiD_Gg7A9QigtHGpO9MMT_4j-gEb438v</recordid><startdate>20110113</startdate><enddate>20110113</enddate><creator>Jiang, Xiong-Jie</creator><creator>Yeung, Sin-Lui</creator><creator>Lo, Pui-Chi</creator><creator>Fong, Wing-Ping</creator><creator>Ng, Dennis K. 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P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a380t-f7a7e08729474d97a547d81e6808ac2d6d50728bb14b581bca7295da719605a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Drug Screening Assays, Antitumor</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - chemistry</topic><topic>Indoles - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>Photochemotherapy</topic><topic>Photosensitizing Agents - chemical synthesis</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Polyamines - chemical synthesis</topic><topic>Polyamines - chemistry</topic><topic>Polyamines - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Xiong-Jie</creatorcontrib><creatorcontrib>Yeung, Sin-Lui</creatorcontrib><creatorcontrib>Lo, Pui-Chi</creatorcontrib><creatorcontrib>Fong, Wing-Ping</creatorcontrib><creatorcontrib>Ng, Dennis K. 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Chem</addtitle><date>2011-01-13</date><risdate>2011</risdate><volume>54</volume><issue>1</issue><spage>320</spage><epage>330</epage><pages>320-330</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>A series of silicon(IV) phthalocyanines substituted axially with different polyamine moieties have been prepared. Their fluorescence quantum yields (ΦF = 0.03−0.08) in N,N-dimethylformamide are low because of reductive quenching by the amino moieties. The values are significantly increased in aqueous media (ΦF = 0.12−0.21) as a result of protonation of the amino substituents. All the compounds are highly photocytotoxic against human colon adenocarcinoma HT29 cells and Chinese hamster ovary cells with IC50 values as low as 1.1 nM. Flow cytometric studies of two selected compounds (2 and 5) against HT29 cells have shown that they induce apoptosis extensively. As shown by confocal microscopy, these two compounds also show high affinity toward the lysosomes, but not the mitochondria, of the cells. Their in vivo photodynamic activity has also been investigated using HT29 tumor bearing nude mice. Both of them can effectively inhibit the growth of the tumor without causing apparent injury to the liver of the mice.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>21138268</pmid><doi>10.1021/jm101253v</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Apoptosis - drug effects CHO Cells Cricetinae Cricetulus Drug Screening Assays, Antitumor HT29 Cells Humans Indoles - chemical synthesis Indoles - chemistry Indoles - pharmacology Male Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Photochemotherapy Photosensitizing Agents - chemical synthesis Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Polyamines - chemical synthesis Polyamines - chemistry Polyamines - pharmacology Structure-Activity Relationship Transplantation, Heterologous |
| title | Phthalocyanine−Polyamine Conjugates as Highly Efficient Photosensitizers for Photodynamic Therapy |
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