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Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species
| Resumo: | This study focused on the research of new bioactive constituents from four species of the Plectranthus plants. Previous works on plants of the genus Plectranthus (Lamiaceæ) evidenced that some of their constituents possess interesting biological activities. The antimicrobial activity of the plant extracts and of the isolated metabolites was thoroughly searched. Antioxidant, anticholinesterase and anti-inflammatory properties of some compounds were also screened. The phytochemical study of the acetone extracts of Plectranthus ornatus Codd., P. ecklonii Benth., P. porcatus Winter & Van Jaarsv and P. saccatus Benth. rendered several terpenoid constituents mostly diterpenes. From P. ornatus three new forskolin-like labdane diterpenes (6-O-acetylforskolin, 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin), a new diterpene with the rare halimane skeleton (11R*-acetoxyhalima-5,13E-dien-15-oic acid), and two known labdane diterpenes were isolated; the rhinocerotinoic acid which was found in Plectranthus species for the first time, and plectrornatin C. Six known triterpenoids were also identified as mixtures. The study of P. ecklonii led to the isolation of two known abietanes, sugiol and parvifloron D. Sugiol was obtained from Plectranthus species for the first time. Four known triterpenoids were also identified as mixtures. P. porcatus, a plant not hitherto studied, yield a new spiro-abietane diterpene [(13S,15S)-6β,7α,12α,19-tetrahydroxy-13β,16-cyclo-8-abietene-11,14-dione]. A new beyerane diterpene (ent-7α-acetoxy-15-beyeren-18-oic acid) was isolated from P. saccatus. Attempting to find novel bioactive prototypes from the more potent antibacterial diterpenes, isolated in higher yields, some diterpene derivatives were prepared. Nine new derivatives were obtained from (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (P. ornatus). A new 2β-(4-hydroxy)benzoyloxy derivative of microstegiol was prepared from parvifloron D (P. ecklonii). From the 7α-acetoxy-6β-hydroxyroyleanone (isolated in the past from P. grandidentatus) thirteen ester derivatives were synthesized, whereof ten were new compounds. The unequivocal chemical structures of pure compounds (natural and derivatives) were deduced from their spectroscopic (IR, MS, 1D and 2D NMR experiments) and physico-chemical data, as well as from literature information. The preliminary antimicrobial activity screenings of all the isolated metabolites showed that several diterpenes inhibited the growth of the Gram positive bacteria tested. In addition, the minimum inhibitory concentration against standard and clinical isolates of sensitive and resistant Staphylococcus and Enterococcus strains was determined for the antibacterial metabolites and their synthesized derivatives. The (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid and its (11R*,13E)-halima-5,13-diene-11,15-diol derivative were the more active halimanes. Parvifloron D was less active than its microstegiol 2β-(4-hydroxy)benzoate derivative, but both showed more potent antibacterial activities than the halimane diterpenoids. The three 12-O-benzoyl esters derivatives of the 7α-acetoxy-6β-hydroxyroyleanone prototype revealed to be more potent growth inhibitors against Staphylococcus and Enterococcus strains than the prototype. The 6β-propionyloxy-12-O-propionyl derivative also showed to be more active against Enterococcus than the viii prototype. Generally, the 12-esters and the 6,12-diesters were more active against Enterococcus than Staphylococcus strains. The hydrophobic extra-interactions with the bacterial targets seem to play an important role on the activity of royleanones derivatives prepared. Taking into account the IC50 values which expressed the scavenging DPPH radical ability, the isolated metabolite parvifloron D as well as 7α-acetoxy-6β-hydroxyroyleanone showed in vitro antioxidant activity. The in vitro acetylcholinesterase assay did not detect any activity for all the newly isolated diterpenes and 7α-acetoxy-6β-hydroxyroyleanone. The COX inhibitor screening assay was tested on 6-O-acetylforskolin, rhinocerotinoic acid, plectrornatin C, (11R*,13E)-halima-5,13-diene-11,15- diol, 11R*-acetoxyhalima-5,13E-dien-15-oic acid and on its methyl ester, for their ability to inhibit COX-2. The preliminary results encourage further studies aiming to confirm and to examine its potential anti-inflammatory activity in a more robust approach. |
|---|---|
| Autores principais: | Rijo, Patricia |
| Assunto: | Teses de doutoramento - 2011 |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1877770281375760384 |
|---|---|
| author | Rijo, Patricia |
| author_facet | Rijo, Patricia |
| author_role | author |
| contributor_name_str_mv | Simões, Maria de Fátima Dias Alfaiate, 1951- Pinheiro, Lídia Maria Veloso, 1960- Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Rijo, Patricia\",\"Person.identifier.cienciaID\":\"851A-88C2-0D45\",\"Person.identifier.orcid\":\"0000-0001-7992-8343\",\"Person.identifier.researcherID\":\"O-2657-2015\",\"Person.identifier.scopusAuthorID\":\"8600601700\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Simões, Maria de Fátima Dias Alfaiate, 1951- Pinheiro, Lídia Maria Veloso, 1960- Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Rijo, Patricia |
| datacite.date.Accepted.fl_str_mv | 2011-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2011-03-28T16:01:21Z |
| datacite.date.embargoed.fl_str_mv | 2011-03-28T16:01:21Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Teses de doutoramento - 2011 |
| datacite.titles.title.fl_str_mv | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| dc.contributor.none.fl_str_mv | Simões, Maria de Fátima Dias Alfaiate, 1951- Pinheiro, Lídia Maria Veloso, 1960- Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Rijo, Patricia |
| dc.date.Accepted.fl_str_mv | 2011-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2011-03-28T16:01:21Z |
| dc.date.embargoed.fl_str_mv | 2011-03-28T16:01:21Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/2833 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Teses de doutoramento - 2011 |
| dc.title.fl_str_mv | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_db06 |
| description | This study focused on the research of new bioactive constituents from four species of the Plectranthus plants. Previous works on plants of the genus Plectranthus (Lamiaceæ) evidenced that some of their constituents possess interesting biological activities. The antimicrobial activity of the plant extracts and of the isolated metabolites was thoroughly searched. Antioxidant, anticholinesterase and anti-inflammatory properties of some compounds were also screened. The phytochemical study of the acetone extracts of Plectranthus ornatus Codd., P. ecklonii Benth., P. porcatus Winter & Van Jaarsv and P. saccatus Benth. rendered several terpenoid constituents mostly diterpenes. From P. ornatus three new forskolin-like labdane diterpenes (6-O-acetylforskolin, 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin), a new diterpene with the rare halimane skeleton (11R*-acetoxyhalima-5,13E-dien-15-oic acid), and two known labdane diterpenes were isolated; the rhinocerotinoic acid which was found in Plectranthus species for the first time, and plectrornatin C. Six known triterpenoids were also identified as mixtures. The study of P. ecklonii led to the isolation of two known abietanes, sugiol and parvifloron D. Sugiol was obtained from Plectranthus species for the first time. Four known triterpenoids were also identified as mixtures. P. porcatus, a plant not hitherto studied, yield a new spiro-abietane diterpene [(13S,15S)-6β,7α,12α,19-tetrahydroxy-13β,16-cyclo-8-abietene-11,14-dione]. A new beyerane diterpene (ent-7α-acetoxy-15-beyeren-18-oic acid) was isolated from P. saccatus. Attempting to find novel bioactive prototypes from the more potent antibacterial diterpenes, isolated in higher yields, some diterpene derivatives were prepared. Nine new derivatives were obtained from (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (P. ornatus). A new 2β-(4-hydroxy)benzoyloxy derivative of microstegiol was prepared from parvifloron D (P. ecklonii). From the 7α-acetoxy-6β-hydroxyroyleanone (isolated in the past from P. grandidentatus) thirteen ester derivatives were synthesized, whereof ten were new compounds. The unequivocal chemical structures of pure compounds (natural and derivatives) were deduced from their spectroscopic (IR, MS, 1D and 2D NMR experiments) and physico-chemical data, as well as from literature information. The preliminary antimicrobial activity screenings of all the isolated metabolites showed that several diterpenes inhibited the growth of the Gram positive bacteria tested. In addition, the minimum inhibitory concentration against standard and clinical isolates of sensitive and resistant Staphylococcus and Enterococcus strains was determined for the antibacterial metabolites and their synthesized derivatives. The (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid and its (11R*,13E)-halima-5,13-diene-11,15-diol derivative were the more active halimanes. Parvifloron D was less active than its microstegiol 2β-(4-hydroxy)benzoate derivative, but both showed more potent antibacterial activities than the halimane diterpenoids. The three 12-O-benzoyl esters derivatives of the 7α-acetoxy-6β-hydroxyroyleanone prototype revealed to be more potent growth inhibitors against Staphylococcus and Enterococcus strains than the prototype. The 6β-propionyloxy-12-O-propionyl derivative also showed to be more active against Enterococcus than the viii prototype. Generally, the 12-esters and the 6,12-diesters were more active against Enterococcus than Staphylococcus strains. The hydrophobic extra-interactions with the bacterial targets seem to play an important role on the activity of royleanones derivatives prepared. Taking into account the IC50 values which expressed the scavenging DPPH radical ability, the isolated metabolite parvifloron D as well as 7α-acetoxy-6β-hydroxyroyleanone showed in vitro antioxidant activity. The in vitro acetylcholinesterase assay did not detect any activity for all the newly isolated diterpenes and 7α-acetoxy-6β-hydroxyroyleanone. The COX inhibitor screening assay was tested on 6-O-acetylforskolin, rhinocerotinoic acid, plectrornatin C, (11R*,13E)-halima-5,13-diene-11,15- diol, 11R*-acetoxyhalima-5,13E-dien-15-oic acid and on its methyl ester, for their ability to inhibit COX-2. The preliminary results encourage further studies aiming to confirm and to examine its potential anti-inflammatory activity in a more robust approach. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/49e17117-67cb-43fb-9c32-d07ba5368fed/download |
| id | ul_32bd7a68b9d1cf3e396d0a7428bd07fb |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/2833 |
| inst_facet_str | urn:organizationAcronym:ul{{{_:::_}}}Universidade de Lisboa |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/2833 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Rijo, Patricia Rijo, Patricia https://www.ciencia-id.pt/851A-88C2-0D45 851A-88C2-0D45 http://orcid.org/0000-0001-7992-8343 0000-0001-7992-8343 |
| publishDate | 2011 |
| repo_facet_str | urn:repositoryAcronym:ul{{{_:::_}}}Repositório da Universidade de Lisboa |
| reponame_str | Repositório da Universidade de Lisboa |
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| spelling | engporThis study focused on the research of new bioactive constituents from four species of the Plectranthus plants. Previous works on plants of the genus Plectranthus (Lamiaceæ) evidenced that some of their constituents possess interesting biological activities. The antimicrobial activity of the plant extracts and of the isolated metabolites was thoroughly searched. Antioxidant, anticholinesterase and anti-inflammatory properties of some compounds were also screened. The phytochemical study of the acetone extracts of Plectranthus ornatus Codd., P. ecklonii Benth., P. porcatus Winter & Van Jaarsv and P. saccatus Benth. rendered several terpenoid constituents mostly diterpenes. From P. ornatus three new forskolin-like labdane diterpenes (6-O-acetylforskolin, 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin), a new diterpene with the rare halimane skeleton (11R*-acetoxyhalima-5,13E-dien-15-oic acid), and two known labdane diterpenes were isolated; the rhinocerotinoic acid which was found in Plectranthus species for the first time, and plectrornatin C. Six known triterpenoids were also identified as mixtures. The study of P. ecklonii led to the isolation of two known abietanes, sugiol and parvifloron D. Sugiol was obtained from Plectranthus species for the first time. Four known triterpenoids were also identified as mixtures. P. porcatus, a plant not hitherto studied, yield a new spiro-abietane diterpene [(13S,15S)-6β,7α,12α,19-tetrahydroxy-13β,16-cyclo-8-abietene-11,14-dione]. A new beyerane diterpene (ent-7α-acetoxy-15-beyeren-18-oic acid) was isolated from P. saccatus. Attempting to find novel bioactive prototypes from the more potent antibacterial diterpenes, isolated in higher yields, some diterpene derivatives were prepared. Nine new derivatives were obtained from (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (P. ornatus). A new 2β-(4-hydroxy)benzoyloxy derivative of microstegiol was prepared from parvifloron D (P. ecklonii). From the 7α-acetoxy-6β-hydroxyroyleanone (isolated in the past from P. grandidentatus) thirteen ester derivatives were synthesized, whereof ten were new compounds. The unequivocal chemical structures of pure compounds (natural and derivatives) were deduced from their spectroscopic (IR, MS, 1D and 2D NMR experiments) and physico-chemical data, as well as from literature information. The preliminary antimicrobial activity screenings of all the isolated metabolites showed that several diterpenes inhibited the growth of the Gram positive bacteria tested. In addition, the minimum inhibitory concentration against standard and clinical isolates of sensitive and resistant Staphylococcus and Enterococcus strains was determined for the antibacterial metabolites and their synthesized derivatives. The (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid and its (11R*,13E)-halima-5,13-diene-11,15-diol derivative were the more active halimanes. Parvifloron D was less active than its microstegiol 2β-(4-hydroxy)benzoate derivative, but both showed more potent antibacterial activities than the halimane diterpenoids. The three 12-O-benzoyl esters derivatives of the 7α-acetoxy-6β-hydroxyroyleanone prototype revealed to be more potent growth inhibitors against Staphylococcus and Enterococcus strains than the prototype. The 6β-propionyloxy-12-O-propionyl derivative also showed to be more active against Enterococcus than the viii prototype. Generally, the 12-esters and the 6,12-diesters were more active against Enterococcus than Staphylococcus strains. The hydrophobic extra-interactions with the bacterial targets seem to play an important role on the activity of royleanones derivatives prepared. Taking into account the IC50 values which expressed the scavenging DPPH radical ability, the isolated metabolite parvifloron D as well as 7α-acetoxy-6β-hydroxyroyleanone showed in vitro antioxidant activity. The in vitro acetylcholinesterase assay did not detect any activity for all the newly isolated diterpenes and 7α-acetoxy-6β-hydroxyroyleanone. The COX inhibitor screening assay was tested on 6-O-acetylforskolin, rhinocerotinoic acid, plectrornatin C, (11R*,13E)-halima-5,13-diene-11,15- diol, 11R*-acetoxyhalima-5,13E-dien-15-oic acid and on its methyl ester, for their ability to inhibit COX-2. The preliminary results encourage further studies aiming to confirm and to examine its potential anti-inflammatory activity in a more robust approach.application/pdfenPhytochemical study and biological activities of diterpenes and derivatives from Plectranthus speciesPersonalRijo, PatriciaDSpacehttp://dspace.org/items/ff1a1f07-7749-4cfc-b97f-f741770904b0DSpacehttp://dspace.org/items/ff1a1f07-7749-4cfc-b97f-f741770904b0RijoPatrícia Dias de MendonçaCiência IDhttps://www.ciencia-id.pt851A-88C2-0D45ORCIDhttp://orcid.org0000-0001-7992-8343Researcher IDhttps://www.researcherid.comO-2657-2015Scopus Author IDhttps://www.scopus.com8600601700Simões, Maria de Fátima Dias Alfaiate, 1951-Pinheiro, Lídia Maria Veloso, 1960-HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@ulisboa.ptrepositorio@ulisboa.pt2011-03-28T16:01:21Z20112011-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/2833http://purl.org/coar/access_right/c_abf2open accessTeses de doutoramento - 20116255372 bytesliteraturehttp://purl.org/coar/resource_type/c_db06doctoral thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/49e17117-67cb-43fb-9c32-d07ba5368fed/download |
| spellingShingle | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species Rijo, Patricia Teses de doutoramento - 2011 |
| status | SINGLETON |
| subject.fl_str_mv | Teses de doutoramento - 2011 |
| title | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| title_full | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| title_fullStr | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| title_full_unstemmed | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| title_short | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| title_sort | Phytochemical study and biological activities of diterpenes and derivatives from Plectranthus species |
| topic | Teses de doutoramento - 2011 |
| topic_facet | Teses de doutoramento - 2011 |
| url | http://hdl.handle.net/10451/2833 |
| visible | 1 |
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