Van der Westhuyzen, Christiaan WHaynes, JPanayides, Jenny-LeeWiid, IParkinson, C2021-03-292021-03-292020Van der Westhuyzen, C.W., Haynes, J., Panayides, J., Wiid, I. & Parkinson, C. 2020. Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis. <i>Medicinal Chemistry, 16(3).</i> http://hdl.handle.net/10204/119271573-40641875-6638http://hdl.handle.net/10204/11927Background: With few exceptions, existing tuberculosis drugs were developed many years ago and resistance profiles have emerged. This has created a need for new drugs with discrete modes of action. There is evidence that tuberculosis (like other bacteria) is susceptible to oxidative pressure and this has yet to be properly utilised as a therapeutic approach in a manner similar to that which has proven highly successful in malaria therapy. Objective: To develop an alternative approach to the incorporation of bacterial siderophores that results in the creation of antitubercular peroxidic leads for subsequent development as novel agents against tuberculosis. Methods: Eight novel peroxides were prepared and the antitubercular activity (H37Rv) was compared to existing artemisinin derivatives in vitro. The potential for toxicity was evaluated against the L6 rat skeletal myoblast and HeLa cervical cancer lines in vitro. Results: The addition of a pyrimidinyl residue to an artemisinin or, preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. Conclusion: The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be a useful approach for creating oxidative drugs to target tuberculosis.AbstractenAntitubercular activityArtemisininMycobacterium tuberculosisPeroxidePyrimidineTetraoxaneArticleVan der Westhuyzen, C. W., Haynes, J., Panayides, J., Wiid, I., & Parkinson, C. (2020). Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis. <i>Medicinal Chemistry, 16(3)</i>, http://hdl.handle.net/10204/11927Van der Westhuyzen, Christiaan W, J Haynes, Jenny-Lee Panayides, I Wiid, and C Parkinson "Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis." <i>Medicinal Chemistry, 16(3)</i> (2020) http://hdl.handle.net/10204/11927Van der Westhuyzen CW, Haynes J, Panayides J, Wiid I, Parkinson C. Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis. Medicinal Chemistry, 16(3). 2020; http://hdl.handle.net/10204/11927.TY - Article AU - Van der Westhuyzen, Christiaan W AU - Haynes, J AU - Panayides, Jenny-Lee AU - Wiid, I AU - Parkinson, C AB - Background: With few exceptions, existing tuberculosis drugs were developed many years ago and resistance profiles have emerged. This has created a need for new drugs with discrete modes of action. There is evidence that tuberculosis (like other bacteria) is susceptible to oxidative pressure and this has yet to be properly utilised as a therapeutic approach in a manner similar to that which has proven highly successful in malaria therapy. Objective: To develop an alternative approach to the incorporation of bacterial siderophores that results in the creation of antitubercular peroxidic leads for subsequent development as novel agents against tuberculosis. Methods: Eight novel peroxides were prepared and the antitubercular activity (H37Rv) was compared to existing artemisinin derivatives in vitro. The potential for toxicity was evaluated against the L6 rat skeletal myoblast and HeLa cervical cancer lines in vitro. Results: The addition of a pyrimidinyl residue to an artemisinin or, preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. Conclusion: The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be a useful approach for creating oxidative drugs to target tuberculosis. DA - 2020 DB - ResearchSpace DP - CSIR J1 - Medicinal Chemistry, 16(3) KW - Antitubercular activity KW - Artemisinin KW - Mycobacterium tuberculosis KW - Peroxide KW - Pyrimidine KW - Tetraoxane LK - https://researchspace.csir.co.za PY - 2020 SM - 1573-4064 SM - 1875-6638 T1 - Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis TI - Anti-mycobacterial peroxides: A new class of agents for development against tuberculosis UR - http://hdl.handle.net/10204/11927 ER -24360