Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells
A series of 14 conjugates of 2α,3β,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, β-alanine, or 11-aminoundecanoic acid) at position C-3. The conj...
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| creator | Tran, Chien Van Tran, Thao Thi Phuong Nguyen, Anh The Tran, Loc Van Pham, Ninh Thi Nguyen, Luu Thi Nguyen, Dung Thi Garrett, Michelle D Nguyen, Nga Thi Do, Thao Thi Serpell, Christopher J Tran, Sung Van |
| description | A series of 14 conjugates of 2α,3β,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, β-alanine, or 11-aminoundecanoic acid) at position C-3. The conjugates were tested
in vitro
for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound
8
, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile
versus
madecassic acid alone.
Madecassic acid and silybin have been conjoined to produce hybrid compounds with improved and different activity against liver cancer cells. |
| doi_str_mv | 10.1039/d4md00170b |
| format | Article |
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in vitro
for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound
8
, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile
versus
madecassic acid alone.
Madecassic acid and silybin have been conjoined to produce hybrid compounds with improved and different activity against liver cancer cells.</description><identifier>ISSN: 2632-8682</identifier><identifier>ISSN: 2040-2503</identifier><identifier>EISSN: 2632-8682</identifier><identifier>EISSN: 2040-2511</identifier><identifier>DOI: 10.1039/d4md00170b</identifier><identifier>PMID: 39185454</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Alanine ; Amino acids ; Apoptosis ; Biological activity ; Biological effects ; Caspase-3 ; Cell cycle ; Conjugates ; Cytotoxicity ; Glycine ; Hepatocellular carcinoma ; Hepatocytes ; Liver cancer ; S phase ; Synthesis ; Toxicity testing ; Tumor cell lines</subject><ispartof>MedChemComm, 2024-10, Vol.15 (1), p.3418-3432</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c262t-cd84d17fe62b1769a458ec2d20a77b34607dd19f37838e42f0fcbddf218d066e3</cites><orcidid>0000-0002-8760-264X ; 0000-0002-2848-9077</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39185454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tran, Chien Van</creatorcontrib><creatorcontrib>Tran, Thao Thi Phuong</creatorcontrib><creatorcontrib>Nguyen, Anh The</creatorcontrib><creatorcontrib>Tran, Loc Van</creatorcontrib><creatorcontrib>Pham, Ninh Thi</creatorcontrib><creatorcontrib>Nguyen, Luu Thi</creatorcontrib><creatorcontrib>Nguyen, Dung Thi</creatorcontrib><creatorcontrib>Garrett, Michelle D</creatorcontrib><creatorcontrib>Nguyen, Nga Thi</creatorcontrib><creatorcontrib>Do, Thao Thi</creatorcontrib><creatorcontrib>Serpell, Christopher J</creatorcontrib><creatorcontrib>Tran, Sung Van</creatorcontrib><title>Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells</title><title>MedChemComm</title><addtitle>RSC Med Chem</addtitle><description>A series of 14 conjugates of 2α,3β,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, β-alanine, or 11-aminoundecanoic acid) at position C-3. The conjugates were tested
in vitro
for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound
8
, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile
versus
madecassic acid alone.
Madecassic acid and silybin have been conjoined to produce hybrid compounds with improved and different activity against liver cancer cells.</description><subject>Alanine</subject><subject>Amino acids</subject><subject>Apoptosis</subject><subject>Biological activity</subject><subject>Biological effects</subject><subject>Caspase-3</subject><subject>Cell cycle</subject><subject>Conjugates</subject><subject>Cytotoxicity</subject><subject>Glycine</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Liver cancer</subject><subject>S phase</subject><subject>Synthesis</subject><subject>Toxicity testing</subject><subject>Tumor cell lines</subject><issn>2632-8682</issn><issn>2040-2503</issn><issn>2632-8682</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpdkUtLxDAUhYMozjDOxr1ScCNCNa8m6VJnfMGIC3Vd0iTVDG0zJu1g_72dh6O4OpdzPy6HcwE4RvASQZJeaVppCBGH-R4YYkZwLJjA-3_mARiHMIcQ4gQhlqSHYEBSJBKa0CEwL13dfJhgQyRrHamucY37siqSqrFL23SRK6JKaqNkCGvb6jjYssttHSlXz9t32Zh-qhaurXWIeru0S-MjJWu1ElOW4QgcFLIMZrzVEXi7u32dPMSz5_vHyfUsVpjhJlZaUI14YRjOEWeppIkwCmsMJec5oQxyrVFaEC6IMBQXsFC51gVGQkPGDBmB883dhXefrQlNVtmwSiBr49qQEZhylGDOcY-e_UPnrvV1ny4jCHGCKaKopy42lPIuBG-KbOFtJX2XIZit-s-m9Gm67v-mh0-3J9u8MnqH_rTdAycbwAe12_4-kHwDwZuKVQ</recordid><startdate>20241017</startdate><enddate>20241017</enddate><creator>Tran, Chien Van</creator><creator>Tran, Thao Thi Phuong</creator><creator>Nguyen, Anh The</creator><creator>Tran, Loc Van</creator><creator>Pham, Ninh Thi</creator><creator>Nguyen, Luu Thi</creator><creator>Nguyen, Dung Thi</creator><creator>Garrett, Michelle D</creator><creator>Nguyen, Nga Thi</creator><creator>Do, Thao Thi</creator><creator>Serpell, Christopher J</creator><creator>Tran, Sung Van</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8760-264X</orcidid><orcidid>https://orcid.org/0000-0002-2848-9077</orcidid></search><sort><creationdate>20241017</creationdate><title>Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells</title><author>Tran, Chien Van ; Tran, Thao Thi Phuong ; Nguyen, Anh The ; Tran, Loc Van ; Pham, Ninh Thi ; Nguyen, Luu Thi ; Nguyen, Dung Thi ; Garrett, Michelle D ; Nguyen, Nga Thi ; Do, Thao Thi ; Serpell, Christopher J ; Tran, Sung Van</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c262t-cd84d17fe62b1769a458ec2d20a77b34607dd19f37838e42f0fcbddf218d066e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alanine</topic><topic>Amino acids</topic><topic>Apoptosis</topic><topic>Biological activity</topic><topic>Biological effects</topic><topic>Caspase-3</topic><topic>Cell cycle</topic><topic>Conjugates</topic><topic>Cytotoxicity</topic><topic>Glycine</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatocytes</topic><topic>Liver cancer</topic><topic>S phase</topic><topic>Synthesis</topic><topic>Toxicity testing</topic><topic>Tumor cell lines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tran, Chien Van</creatorcontrib><creatorcontrib>Tran, Thao Thi Phuong</creatorcontrib><creatorcontrib>Nguyen, Anh The</creatorcontrib><creatorcontrib>Tran, Loc Van</creatorcontrib><creatorcontrib>Pham, Ninh Thi</creatorcontrib><creatorcontrib>Nguyen, Luu Thi</creatorcontrib><creatorcontrib>Nguyen, Dung Thi</creatorcontrib><creatorcontrib>Garrett, Michelle D</creatorcontrib><creatorcontrib>Nguyen, Nga Thi</creatorcontrib><creatorcontrib>Do, Thao Thi</creatorcontrib><creatorcontrib>Serpell, Christopher J</creatorcontrib><creatorcontrib>Tran, Sung Van</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tran, Chien Van</au><au>Tran, Thao Thi Phuong</au><au>Nguyen, Anh The</au><au>Tran, Loc Van</au><au>Pham, Ninh Thi</au><au>Nguyen, Luu Thi</au><au>Nguyen, Dung Thi</au><au>Garrett, Michelle D</au><au>Nguyen, Nga Thi</au><au>Do, Thao Thi</au><au>Serpell, Christopher J</au><au>Tran, Sung Van</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells</atitle><jtitle>MedChemComm</jtitle><addtitle>RSC Med Chem</addtitle><date>2024-10-17</date><risdate>2024</risdate><volume>15</volume><issue>1</issue><spage>3418</spage><epage>3432</epage><pages>3418-3432</pages><issn>2632-8682</issn><issn>2040-2503</issn><eissn>2632-8682</eissn><eissn>2040-2511</eissn><abstract>A series of 14 conjugates of 2α,3β,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, β-alanine, or 11-aminoundecanoic acid) at position C-3. The conjugates were tested
in vitro
for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound
8
, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile
versus
madecassic acid alone.
Madecassic acid and silybin have been conjoined to produce hybrid compounds with improved and different activity against liver cancer cells.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>39185454</pmid><doi>10.1039/d4md00170b</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8760-264X</orcidid><orcidid>https://orcid.org/0000-0002-2848-9077</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2632-8682 |
| ispartof | MedChemComm, 2024-10, Vol.15 (1), p.3418-3432 |
| issn | 2632-8682 2040-2503 2632-8682 2040-2511 |
| language | eng |
| recordid | cdi_pubmed_primary_39185454 |
| source | Royal Society Of Chemistry Journals 2008- |
| subjects | Alanine Amino acids Apoptosis Biological activity Biological effects Caspase-3 Cell cycle Conjugates Cytotoxicity Glycine Hepatocellular carcinoma Hepatocytes Liver cancer S phase Synthesis Toxicity testing Tumor cell lines |
| title | Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells |
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