Synthesis of aza homologues of folic acid
Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei...
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| Veröffentlicht in: | Journal of medicinal chemistry 1979-07, Vol.22 (7), p.874 |
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| container_title | Journal of medicinal chemistry |
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| creator | Martinelli, J E Chaykovsky, M Kisliuk, R L Gaumont, Y |
| description | Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase. |
| doi_str_mv | 10.1021/jm00193a023 |
| format | Article |
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None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase.</description><identifier>ISSN: 0022-2623</identifier><identifier>DOI: 10.1021/jm00193a023</identifier><identifier>PMID: 109617</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antineoplastic Agents - chemical synthesis ; Folic Acid - analogs & derivatives ; Folic Acid - chemical synthesis ; Folic Acid - therapeutic use ; Humans ; In Vitro Techniques ; Lactobacillus casei - drug effects ; Lactobacillus casei - enzymology ; Lactobacillus casei - growth & development ; Leukemia L1210 - drug therapy ; Leukemia, Lymphoid - drug therapy ; Male ; Mice ; Pediococcus - drug effects ; Pediococcus - growth & development ; Streptococcus - drug effects ; Streptococcus - growth & development ; Thymidylate Synthase - antagonists & inhibitors</subject><ispartof>Journal of medicinal chemistry, 1979-07, Vol.22 (7), p.874</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/109617$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martinelli, J E</creatorcontrib><creatorcontrib>Chaykovsky, M</creatorcontrib><creatorcontrib>Kisliuk, R L</creatorcontrib><creatorcontrib>Gaumont, Y</creatorcontrib><title>Synthesis of aza homologues of folic acid</title><title>Journal of medicinal chemistry</title><addtitle>J Med Chem</addtitle><description>Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase.</description><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Folic Acid - analogs & derivatives</subject><subject>Folic Acid - chemical synthesis</subject><subject>Folic Acid - therapeutic use</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Lactobacillus casei - drug effects</subject><subject>Lactobacillus casei - enzymology</subject><subject>Lactobacillus casei - growth & development</subject><subject>Leukemia L1210 - drug therapy</subject><subject>Leukemia, Lymphoid - drug therapy</subject><subject>Male</subject><subject>Mice</subject><subject>Pediococcus - drug effects</subject><subject>Pediococcus - growth & development</subject><subject>Streptococcus - drug effects</subject><subject>Streptococcus - growth & development</subject><subject>Thymidylate Synthase - antagonists & inhibitors</subject><issn>0022-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1979</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNotjj1PAkEUALcAEdDK1uJai9P39uvulYaImpBQSE_e7YccuXMvLBT4602EapIpJiPEA8IzgsSXfQ-ApBikGokpgJSltFLdilnOewBQKNVE3CCQxWoqnr7OP8ddyG0uUiz4l4td6lOXvk_h38TUta5g1_o7MY7c5XB_5Vxslm-bxUe5Wr9_Ll5X5YASjmUVDbjglOEmMoGxFm2IWtemDtoxojYeAdiRrZwiX9sqEoEm8A0Sqbl4vGSHU9MHvx0Obc-H8_YyrP4A8KM-GA</recordid><startdate>197907</startdate><enddate>197907</enddate><creator>Martinelli, J E</creator><creator>Chaykovsky, M</creator><creator>Kisliuk, R L</creator><creator>Gaumont, Y</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>197907</creationdate><title>Synthesis of aza homologues of folic acid</title><author>Martinelli, J E ; Chaykovsky, M ; Kisliuk, R L ; Gaumont, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p120t-7f50cec35abfa9056616ef44858e4ca1145d100ac967c39d867f990490db1993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1979</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Folic Acid - analogs & derivatives</topic><topic>Folic Acid - chemical synthesis</topic><topic>Folic Acid - therapeutic use</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Lactobacillus casei - drug effects</topic><topic>Lactobacillus casei - enzymology</topic><topic>Lactobacillus casei - growth & development</topic><topic>Leukemia L1210 - drug therapy</topic><topic>Leukemia, Lymphoid - drug therapy</topic><topic>Male</topic><topic>Mice</topic><topic>Pediococcus - drug effects</topic><topic>Pediococcus - growth & development</topic><topic>Streptococcus - drug effects</topic><topic>Streptococcus - growth & development</topic><topic>Thymidylate Synthase - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martinelli, J E</creatorcontrib><creatorcontrib>Chaykovsky, M</creatorcontrib><creatorcontrib>Kisliuk, R L</creatorcontrib><creatorcontrib>Gaumont, Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martinelli, J E</au><au>Chaykovsky, M</au><au>Kisliuk, R L</au><au>Gaumont, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of aza homologues of folic acid</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J Med Chem</addtitle><date>1979-07</date><risdate>1979</risdate><volume>22</volume><issue>7</issue><spage>874</spage><pages>874-</pages><issn>0022-2623</issn><abstract>Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase.</abstract><cop>United States</cop><pmid>109617</pmid><doi>10.1021/jm00193a023</doi></addata></record> |
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| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1979-07, Vol.22 (7), p.874 |
| issn | 0022-2623 |
| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | Animals Antineoplastic Agents - chemical synthesis Folic Acid - analogs & derivatives Folic Acid - chemical synthesis Folic Acid - therapeutic use Humans In Vitro Techniques Lactobacillus casei - drug effects Lactobacillus casei - enzymology Lactobacillus casei - growth & development Leukemia L1210 - drug therapy Leukemia, Lymphoid - drug therapy Male Mice Pediococcus - drug effects Pediococcus - growth & development Streptococcus - drug effects Streptococcus - growth & development Thymidylate Synthase - antagonists & inhibitors |
| title | Synthesis of aza homologues of folic acid |
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