{"id":{"repo_id":"strathclyde","oai_identifier":"oai:strathclyde:tq57nr067"},"canonical_url":"https://search.dev.ndltd.org/etd/strathclyde/oai:strathclyde:tq57nr067","repository":{"repo_id":"strathclyde","name":"University of Strathclyde","base_url":"https://stax.strath.ac.uk/catalog/oai"},"display":{"title":"An assessment of the effects of novel anti-inflammatory compounds in cell based studies","abstract":"NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs.","abstract_html":"NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs.","abstract_has_math":false,"creators":["Gafri, Fadia Mohamed"],"institution":"University of Strathclyde","degree_name":"phd","degree_level":"doctoral-pg","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-24T04:48:10Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.48730/gwv9-kr25"],"render_values":[{"text":"10.48730/gwv9-kr25","href":"https://doi.org/10.48730/gwv9-kr25","code":true}]},{"key":"dc:identifier","label":"Identifier","values":["T13435"],"render_values":[{"text":"T13435","href":null,"code":true}]}]},"links":{"outbound_url":"https://stax.strath.ac.uk/concern/theses/tq57nr067","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Gafri, Fadia Mohamed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012"]},{"key":"dc:date.issued","label":"Date","values":["2012"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Strathclyde Institute of Pharmacy and Biomedical Sciences"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Strathclyde"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral-pg"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["T13435"]},{"key":"dc:identifier.doi","label":"DOI","values":["10.48730/gwv9-kr25"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://stax.strath.ac.uk/concern/theses/tq57nr067"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Strathclyde theses - ask staff. Thesis no. : T13435","NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs."]},{"key":"dc:description.abstract","label":"Abstract","values":["NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs."]},{"key":"dc:title","label":"Title","values":["An assessment of the effects of novel anti-inflammatory compounds in cell based studies"]}]}],"canonical_facts":{"dc:creator":["Gafri, Fadia Mohamed"],"dc:date":["2012"],"dc:date.issued":["2012"],"dc:description":["Strathclyde theses - ask staff. Thesis no. : T13435","NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs."],"dc:description.abstract":["NF-κB and AP-1 are transcription factors with an evolutionary conserved role in the triggering and coordination of both innate and adaptive immune responses. Since they regulate a large number of inflammatory genes, they are considered as potential targets for anti-inflammatory drugs. In the current study, natural SU182 and synthetic alkaloid compounds, SU331, SU432 and minor groove binder compounds AIK18/85/1 and AIK18/70 obtained from the library associated with University of Strathclyde CRUK-Small Molecule Drug Discovery (SMDD) were investigated for possible anti-inflammatory effects at μM concentrations. In NCTC2544 human keratinocyte cells stably transfected with either NF-κB- or AP-1-linked luciferase reporter plasmids, tumour necrosis factor-α (TNF-α) and phorbol-12-myristate- 13 acetate (PMA) well characterized stimuli for canonical NF-κB pathway induced NF-κB and AP-1 transcriptional activity respectively. However, all tested compounds inhibited NF-κB transcriptional activity; in particular AIK18/85/1 prevented the TNF-α-induced translocation of NF-κB (p65) to the nucleus assessed by indirect immunoflouresnce. This effect of AIK18/85/1 was also reflected in the significant reduction of nuclear extract NF-κB-DNA binding activity as detected by Electrophoresis Mobility Shift Assay (EMSA), but without affecting the degradation of IκBα protein induced by TNF-α. Furthermore, AIK18/70 also decreased TNF-α- induced NF-κB-DNA binding activity but neither affected the phosphorylation of p65 nor the degradation of IκBα. On the other hand, both SU331 and SU432 inhibited the IκBα loss and resultant NF-κB-DNA binding activity in a concentration dependent manner. Although none of these compounds inhibited TNF-α-induced phosphorylation of NF-κB (Ser536-p65), their mode of inhibition on NF-κB signalling was sufficient to prevent the expression of NF-κB dependent proteins such as COX-2 and iNOS in LPS stimulated RAW 264.7 macrophage cells. Intriguingly, in contrast to other compounds SU182 was only effective at the level of NF-κB and AP-1 transcriptional activities, but without affecting the expression level of iNOS and COX-2 enzymes. Taken together these data indicate the potential for tested compounds to interfere with NF-κB signalling as IKK inhibitors or novel translocation inhibitor and thus may considered to be useful leads for the development of novel anti-inflammatory and anticancer drugs."],"dc:identifier":["T13435"],"dc:identifier.doi":["10.48730/gwv9-kr25"],"dc:identifier.uri":["https://stax.strath.ac.uk/concern/theses/tq57nr067"],"dc:publisher.department":["Strathclyde Institute of Pharmacy and Biomedical Sciences"],"dc:publisher.institution":["University of Strathclyde"],"dc:title":["An assessment of the effects of novel anti-inflammatory compounds in cell based studies"],"dc:type.qualificationlevel":["doctoral-pg"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T04:48:10Z"}