{"id":{"repo_id":"sask","oai_identifier":"oai:harvest.usask.ca:10388/15572"},"canonical_url":"https://search.dev.ndltd.org/etd/sask/oai:harvest.usask.ca:10388/15572","repository":{"repo_id":"sask","name":"University of Saskatchewan","base_url":"https://harvest.usask.ca/server/oai/request"},"display":{"title":"Toxicological and Pharmacological Studies on Amide Derivatives of 5-Methoxymethyl-2'-Deoxycytidine","abstract":"Toxicity has been a major problem in the development of drugs for the treatment of viral infections. Our hypothesis was that deoxycytidine analogs should have lower toxicity profile, because these pharmacophores would act selectively on virus infected cells. The antiviral activity of amide derivatives of 5-Methoxymethy1-2i-deoxycytidine (MMdCyd), namely, acetyl-MMdCyd, propanoyl-MMdCyd, butanoyl-MMdCyd and hexanoyl-MMdCyd against Herpes simplex virus type 1 (HSV-l), in A 549 cells and VERO cells was determined using the plaque reduction assay. The potency of MMdCyd and amide derivatives was higher in A549 cells as compared to VERO cells. Butanoyl-MMdCyd (But-MMdCyd) was the most potent compound in both cell lines. Concentrations of MMdCyd and But-MMdCyd required to inhibit 50% virus plaque formation (ED50) were 6.69 ± 0.70 and 0.87 ± 0.54 μM, respectively, in A549 cells. Butanoyl-MMdCyd was very effective in preventing cytopathogenic effects of HSV-1 and decreasing the production of infectious virus particles. The acute and delayed cytotoxicity of MMdCyd and But-MMdCyd was determined using CEM cells. Dideoxycytidine (ddC) was used as a positive control drug. At a concentration of 0.5 μM, ddC increased the doubling time of the cells, from the fourth day onward. MMdCyd and But-MMdCyd did not alter the doubling time of the cells up to 2000 μM (highest concentration tested).","abstract_html":"Toxicity has been a major problem in the development of drugs for the treatment of viral infections. Our hypothesis was that deoxycytidine analogs should have lower toxicity profile, because these pharmacophores would act selectively on virus infected cells. The antiviral activity of amide derivatives of 5-Methoxymethy1-2i-deoxycytidine (MMdCyd), namely, acetyl-MMdCyd, propanoyl-MMdCyd, butanoyl-MMdCyd and hexanoyl-MMdCyd against Herpes simplex virus type 1 (HSV-l), in A 549 cells and VERO cells was determined using the plaque reduction assay. The potency of MMdCyd and amide derivatives was higher in A549 cells as compared to VERO cells. Butanoyl-MMdCyd (But-MMdCyd) was the most potent compound in both cell lines. Concentrations of MMdCyd and But-MMdCyd required to inhibit 50% virus plaque formation (ED50) were 6.69 ± 0.70 and 0.87 ± 0.54 μM, respectively, in A549 cells. Butanoyl-MMdCyd was very effective in preventing cytopathogenic effects of HSV-1 and decreasing the production of infectious virus particles. The acute and delayed cytotoxicity of MMdCyd and But-MMdCyd was determined using CEM cells. Dideoxycytidine (ddC) was used as a positive control drug. At a concentration of 0.5 μM, ddC increased the doubling time of the cells, from the fourth day onward. MMdCyd and But-MMdCyd did not alter the doubling time of the cells up to 2000 μM (highest concentration tested).","abstract_has_math":false,"creators":["Mannala, Shajan"],"institution":"University of Saskatchewan","degree_name":"Master of Science (M.Sc.)","degree_level":"Masters","degree_discipline":"Toxicology","degree_department":null,"school":null,"contributors":[],"advisors":["Gupta, V.S.","Saxena, A."],"committee_chairs":[],"committee_members":[],"year":1999,"date_issued":"1999","date_published":"1999","updated_at":"2026-07-24T04:27:18Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10388/15572","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gupta, V.S.","Saxena, A."]},{"key":"dc:creator","label":"Author","values":["Mannala, Shajan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-04-09T19:52:25Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-04-09T19:52:25Z"]},{"key":"dc:date.issued","label":"Date","values":["1999"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Toxicology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (M.Sc.)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Saskatchewan"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10388/15572"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Toxicity has been a major problem in the development of drugs for the treatment of viral infections. Our hypothesis was that deoxycytidine analogs should have lower toxicity profile, because these pharmacophores would act selectively on virus infected cells. The antiviral activity of amide derivatives of 5-Methoxymethy1-2i-deoxycytidine (MMdCyd), namely, acetyl-MMdCyd, propanoyl-MMdCyd, butanoyl-MMdCyd and hexanoyl-MMdCyd against Herpes simplex virus type 1 (HSV-l), in A 549 cells and VERO cells was determined using the plaque reduction assay. The potency of MMdCyd and amide derivatives was higher in A549 cells as compared to VERO cells. Butanoyl-MMdCyd (But-MMdCyd) was the most potent compound in both cell lines. Concentrations of MMdCyd and But-MMdCyd required to inhibit 50% virus plaque formation (ED50) were 6.69 ± 0.70 and 0.87 ± 0.54 μM, respectively, in A549 cells. Butanoyl-MMdCyd was very effective in preventing cytopathogenic effects of HSV-1 and decreasing the production of infectious virus particles. The acute and delayed cytotoxicity of MMdCyd and But-MMdCyd was determined using CEM cells. Dideoxycytidine (ddC) was used as a positive control drug. At a concentration of 0.5 μM, ddC increased the doubling time of the cells, from the fourth day onward. MMdCyd and But-MMdCyd did not alter the doubling time of the cells up to 2000 μM (highest concentration tested)."]},{"key":"dc:title","label":"Title","values":["Toxicological and Pharmacological Studies on Amide Derivatives of 5-Methoxymethyl-2'-Deoxycytidine"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gupta, V.S.","Saxena, A."],"dc:creator":["Mannala, Shajan"],"dc:date.accessioned":["2024-04-09T19:52:25Z"],"dc:date.available":["2024-04-09T19:52:25Z"],"dc:date.issued":["1999"],"dc:description.abstract":["Toxicity has been a major problem in the development of drugs for the treatment of viral infections. Our hypothesis was that deoxycytidine analogs should have lower toxicity profile, because these pharmacophores would act selectively on virus infected cells. The antiviral activity of amide derivatives of 5-Methoxymethy1-2i-deoxycytidine (MMdCyd), namely, acetyl-MMdCyd, propanoyl-MMdCyd, butanoyl-MMdCyd and hexanoyl-MMdCyd against Herpes simplex virus type 1 (HSV-l), in A 549 cells and VERO cells was determined using the plaque reduction assay. The potency of MMdCyd and amide derivatives was higher in A549 cells as compared to VERO cells. Butanoyl-MMdCyd (But-MMdCyd) was the most potent compound in both cell lines. Concentrations of MMdCyd and But-MMdCyd required to inhibit 50% virus plaque formation (ED50) were 6.69 ± 0.70 and 0.87 ± 0.54 μM, respectively, in A549 cells. Butanoyl-MMdCyd was very effective in preventing cytopathogenic effects of HSV-1 and decreasing the production of infectious virus particles. The acute and delayed cytotoxicity of MMdCyd and But-MMdCyd was determined using CEM cells. Dideoxycytidine (ddC) was used as a positive control drug. At a concentration of 0.5 μM, ddC increased the doubling time of the cells, from the fourth day onward. MMdCyd and But-MMdCyd did not alter the doubling time of the cells up to 2000 μM (highest concentration tested)."],"dc:identifier.uri":["https://hdl.handle.net/10388/15572"],"dc:title":["Toxicological and Pharmacological Studies on Amide Derivatives of 5-Methoxymethyl-2'-Deoxycytidine"],"thesis:degree_discipline":["Toxicology"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science (M.Sc.)"],"thesis:institution_name":["University of Saskatchewan"]},"updated_at":"2026-07-24T04:27:18Z"}