Pd(II) and Pt(II) saccharinate complexes with two phosphine derivatives: Synthesis, anticancer and antiangiogenic activities
As clinically used anticancer Pt(II) drugs have severe side effects, there is a growing interest for new metal complexes with great potential for cancer therapy. The current work aimed to prepare and characterize new Pd(II) and Pt(II) saccharinate (sac) complexes bearing pyridyl‐ and benzyldiphenylp...
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| creator | Icsel, Ceyda Yilmaz, Veysel T. Aygun, Muhittin Erkisa, Merve Ulukaya, Engin Akar, R. Okan |
| description | As clinically used anticancer Pt(II) drugs have severe side effects, there is a growing interest for new metal complexes with great potential for cancer therapy. The current work aimed to prepare and characterize new Pd(II) and Pt(II) saccharinate (sac) complexes bearing pyridyl‐ and benzyldiphenylphosphines (PPh2Py and PPh2Bz, respectively), cis‐[Pd(sac)2(PPh2Py)2] (1), cis‐[PtCl(sac)(PPh2Py)2]·0.5DMF (2), cis‐[Pd(sac)2(PPh2Bz)2]·DMF (3) and trans‐[PtCl(sac)(PPh2Bz)2] (4) as promising anticancer and antiangiogenic drugs. The anticancer activity of the complexes was screened against seven cancer cell lines including HCT116 (colon), HepG2 (liver), MDA‐MB‐231 (breast), PANC‐1 (pancreatic), A549 (lung), C6 (glioma), DU145 (prostate) and normal human lung epithelial cells (BEAS‐2B). 1 and 2 did not show biological activity below 20 μM at 48 h, whereas 3 and 4 displayed significant cytotoxic effect on the cancer cells. 4 was the most potent complex (IC50 = 2.2–12.1 μM) and displayed much greater cytotoxicity than cisplatin in all the cancer cell lines. 4 caused apoptosis in HCT116 cells as evidenced by annexin V positivity and caspase 3/7 activity assays. Furthermore, the inhibition of antiapoptotic Bcl‐2 proteins by the complex suggested the intrinsic apoptosis. In addition, 4 greatly enhanced generation of intracellular reactive oxygen species (ROS) and consequently caused remarkable DNA double‐strand breaks in HCT116 cells. Moreover, the chick chorioallantoic membrane (CAM) assay was used to evaluate antiangiogenic potential of 4. The complex effectively inhibited angiogenesis at a dose of 50 ng, suggesting it as a promising multi‐targeted agent for antiangiogenic cancer treatment.
A trans‐configured Pt(II) saccharinate complex bearing benzyldiphenylphosphine inhibits both growth of human colorectal carcinoma cells (HCT116) and angiogenesis, acting as a multifunctional anticancer and antiangiogenic agent. |
| doi_str_mv | 10.1002/aoc.7433 |
| format | Article |
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A trans‐configured Pt(II) saccharinate complex bearing benzyldiphenylphosphine inhibits both growth of human colorectal carcinoma cells (HCT116) and angiogenesis, acting as a multifunctional anticancer and antiangiogenic agent.</description><identifier>ISSN: 0268-2605</identifier><identifier>EISSN: 1099-0739</identifier><identifier>DOI: 10.1002/aoc.7433</identifier><language>eng</language><publisher>Chichester: Wiley Subscription Services, Inc</publisher><subject>Antiangiogenics ; anticancer activity ; Anticancer properties ; Apoptosis ; Biological activity ; Cancer therapies ; cell apoptosis ; Coordination compounds ; Epithelium ; Lungs ; Palladium ; palladium(II) and platinum(II) complexes ; Phosphines ; Platinum ; Side effects ; X‐ray structures</subject><ispartof>Applied organometallic chemistry, 2024-05, Vol.38 (5), p.n/a</ispartof><rights>2024 John Wiley & Sons Ltd.</rights><rights>2024 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2543-ddf7f7cca734c5be572ee3aa13bba420193887507a71e931153a70ec9aa591533</cites><orcidid>0000-0002-2717-2430 ; 0000-0002-2849-3332 ; 0000-0003-4875-5472 ; 0000-0001-8687-2034 ; 0000-0001-9670-9062 ; 0000-0002-3127-742X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Faoc.7433$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Faoc.7433$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Icsel, Ceyda</creatorcontrib><creatorcontrib>Yilmaz, Veysel T.</creatorcontrib><creatorcontrib>Aygun, Muhittin</creatorcontrib><creatorcontrib>Erkisa, Merve</creatorcontrib><creatorcontrib>Ulukaya, Engin</creatorcontrib><creatorcontrib>Akar, R. Okan</creatorcontrib><title>Pd(II) and Pt(II) saccharinate complexes with two phosphine derivatives: Synthesis, anticancer and antiangiogenic activities</title><title>Applied organometallic chemistry</title><description>As clinically used anticancer Pt(II) drugs have severe side effects, there is a growing interest for new metal complexes with great potential for cancer therapy. The current work aimed to prepare and characterize new Pd(II) and Pt(II) saccharinate (sac) complexes bearing pyridyl‐ and benzyldiphenylphosphines (PPh2Py and PPh2Bz, respectively), cis‐[Pd(sac)2(PPh2Py)2] (1), cis‐[PtCl(sac)(PPh2Py)2]·0.5DMF (2), cis‐[Pd(sac)2(PPh2Bz)2]·DMF (3) and trans‐[PtCl(sac)(PPh2Bz)2] (4) as promising anticancer and antiangiogenic drugs. The anticancer activity of the complexes was screened against seven cancer cell lines including HCT116 (colon), HepG2 (liver), MDA‐MB‐231 (breast), PANC‐1 (pancreatic), A549 (lung), C6 (glioma), DU145 (prostate) and normal human lung epithelial cells (BEAS‐2B). 1 and 2 did not show biological activity below 20 μM at 48 h, whereas 3 and 4 displayed significant cytotoxic effect on the cancer cells. 4 was the most potent complex (IC50 = 2.2–12.1 μM) and displayed much greater cytotoxicity than cisplatin in all the cancer cell lines. 4 caused apoptosis in HCT116 cells as evidenced by annexin V positivity and caspase 3/7 activity assays. Furthermore, the inhibition of antiapoptotic Bcl‐2 proteins by the complex suggested the intrinsic apoptosis. In addition, 4 greatly enhanced generation of intracellular reactive oxygen species (ROS) and consequently caused remarkable DNA double‐strand breaks in HCT116 cells. Moreover, the chick chorioallantoic membrane (CAM) assay was used to evaluate antiangiogenic potential of 4. The complex effectively inhibited angiogenesis at a dose of 50 ng, suggesting it as a promising multi‐targeted agent for antiangiogenic cancer treatment.
A trans‐configured Pt(II) saccharinate complex bearing benzyldiphenylphosphine inhibits both growth of human colorectal carcinoma cells (HCT116) and angiogenesis, acting as a multifunctional anticancer and antiangiogenic agent.</description><subject>Antiangiogenics</subject><subject>anticancer activity</subject><subject>Anticancer properties</subject><subject>Apoptosis</subject><subject>Biological activity</subject><subject>Cancer therapies</subject><subject>cell apoptosis</subject><subject>Coordination compounds</subject><subject>Epithelium</subject><subject>Lungs</subject><subject>Palladium</subject><subject>palladium(II) and platinum(II) complexes</subject><subject>Phosphines</subject><subject>Platinum</subject><subject>Side effects</subject><subject>X‐ray structures</subject><issn>0268-2605</issn><issn>1099-0739</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kE1Lw0AQhhdRsFbBn7DgpYKps9kk23grxY9CoQX1HKabSbOlTeLutrXgjzdtvXqaeeGZd-Bh7FZAXwCEj1jrvoqkPGMdAWkagJLpOetAmAyCMIH4kl05twSANBFRh_3M8t54fM-xyvnMH1eHWpdoTYWeuK7XzYq-yfGd8SX3u5o3Ze2a0lTEc7Jmi95syT3x933lS3LGPbRl3misNNlj7yFitTD1giqjOer2wnhD7ppdFLhydPM3u-zz5flj9BZMpq_j0XAS6DCOZJDnhSqU1qhkpOM5xSokkohCzucYhSBSORioGBQqQakUIpaogHSKGKdtkF12d-ptbP21IeezZb2xVfsykxDJCBIQSUv1TpS2tXOWiqyxZo12nwnIDm6z1m12cNuiwQndmRXt_-Wy4XR05H8BJLp7KQ</recordid><startdate>202405</startdate><enddate>202405</enddate><creator>Icsel, Ceyda</creator><creator>Yilmaz, Veysel T.</creator><creator>Aygun, Muhittin</creator><creator>Erkisa, Merve</creator><creator>Ulukaya, Engin</creator><creator>Akar, R. 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Okan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2543-ddf7f7cca734c5be572ee3aa13bba420193887507a71e931153a70ec9aa591533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antiangiogenics</topic><topic>anticancer activity</topic><topic>Anticancer properties</topic><topic>Apoptosis</topic><topic>Biological activity</topic><topic>Cancer therapies</topic><topic>cell apoptosis</topic><topic>Coordination compounds</topic><topic>Epithelium</topic><topic>Lungs</topic><topic>Palladium</topic><topic>palladium(II) and platinum(II) complexes</topic><topic>Phosphines</topic><topic>Platinum</topic><topic>Side effects</topic><topic>X‐ray structures</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Icsel, Ceyda</creatorcontrib><creatorcontrib>Yilmaz, Veysel T.</creatorcontrib><creatorcontrib>Aygun, Muhittin</creatorcontrib><creatorcontrib>Erkisa, Merve</creatorcontrib><creatorcontrib>Ulukaya, Engin</creatorcontrib><creatorcontrib>Akar, R. Okan</creatorcontrib><collection>CrossRef</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Applied organometallic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Icsel, Ceyda</au><au>Yilmaz, Veysel T.</au><au>Aygun, Muhittin</au><au>Erkisa, Merve</au><au>Ulukaya, Engin</au><au>Akar, R. Okan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pd(II) and Pt(II) saccharinate complexes with two phosphine derivatives: Synthesis, anticancer and antiangiogenic activities</atitle><jtitle>Applied organometallic chemistry</jtitle><date>2024-05</date><risdate>2024</risdate><volume>38</volume><issue>5</issue><epage>n/a</epage><issn>0268-2605</issn><eissn>1099-0739</eissn><abstract>As clinically used anticancer Pt(II) drugs have severe side effects, there is a growing interest for new metal complexes with great potential for cancer therapy. The current work aimed to prepare and characterize new Pd(II) and Pt(II) saccharinate (sac) complexes bearing pyridyl‐ and benzyldiphenylphosphines (PPh2Py and PPh2Bz, respectively), cis‐[Pd(sac)2(PPh2Py)2] (1), cis‐[PtCl(sac)(PPh2Py)2]·0.5DMF (2), cis‐[Pd(sac)2(PPh2Bz)2]·DMF (3) and trans‐[PtCl(sac)(PPh2Bz)2] (4) as promising anticancer and antiangiogenic drugs. The anticancer activity of the complexes was screened against seven cancer cell lines including HCT116 (colon), HepG2 (liver), MDA‐MB‐231 (breast), PANC‐1 (pancreatic), A549 (lung), C6 (glioma), DU145 (prostate) and normal human lung epithelial cells (BEAS‐2B). 1 and 2 did not show biological activity below 20 μM at 48 h, whereas 3 and 4 displayed significant cytotoxic effect on the cancer cells. 4 was the most potent complex (IC50 = 2.2–12.1 μM) and displayed much greater cytotoxicity than cisplatin in all the cancer cell lines. 4 caused apoptosis in HCT116 cells as evidenced by annexin V positivity and caspase 3/7 activity assays. Furthermore, the inhibition of antiapoptotic Bcl‐2 proteins by the complex suggested the intrinsic apoptosis. In addition, 4 greatly enhanced generation of intracellular reactive oxygen species (ROS) and consequently caused remarkable DNA double‐strand breaks in HCT116 cells. Moreover, the chick chorioallantoic membrane (CAM) assay was used to evaluate antiangiogenic potential of 4. The complex effectively inhibited angiogenesis at a dose of 50 ng, suggesting it as a promising multi‐targeted agent for antiangiogenic cancer treatment.
A trans‐configured Pt(II) saccharinate complex bearing benzyldiphenylphosphine inhibits both growth of human colorectal carcinoma cells (HCT116) and angiogenesis, acting as a multifunctional anticancer and antiangiogenic agent.</abstract><cop>Chichester</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/aoc.7433</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2717-2430</orcidid><orcidid>https://orcid.org/0000-0002-2849-3332</orcidid><orcidid>https://orcid.org/0000-0003-4875-5472</orcidid><orcidid>https://orcid.org/0000-0001-8687-2034</orcidid><orcidid>https://orcid.org/0000-0001-9670-9062</orcidid><orcidid>https://orcid.org/0000-0002-3127-742X</orcidid></addata></record> |
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| subjects | Antiangiogenics anticancer activity Anticancer properties Apoptosis Biological activity Cancer therapies cell apoptosis Coordination compounds Epithelium Lungs Palladium palladium(II) and platinum(II) complexes Phosphines Platinum Side effects X‐ray structures |
| title | Pd(II) and Pt(II) saccharinate complexes with two phosphine derivatives: Synthesis, anticancer and antiangiogenic activities |
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