Autor: Brulíková, L.; Chasák, J.
Název práce v češtině: Design a syntéza nových squaramidů jako selektivních antituberkulotik
Název práce v angličtině: Design and Synthesis of New Squaramides as Selective Antitubercular Agents
Klíčová slova v češtině: squaramidy, tuberkulóza
Klíčová slova v angličtině:squaramides, tuberculosis
Abstrakt česky: Tuberculosis (TB), an infectious disease predominantly caused by the bacillus Mycobacterium tuberculosis (Mtb) still poses a major and enduring global health threat. The infectious disease remains one of the top 10 causes of death and the leading cause of death due to a single infectious agent. In 2017, approximately 10 million people developed active TB disease and over 1.6 million persons died as a result. Furthermore, the epidemic is fuelled by the ever-increasing emergence of anti-TB drug resistance. Without a doubt, the discovery of entirely new compounds with an alternative mechanism of action to the existing therapeutics and directed towards unknown targets of Mtb becomes more and more desirable.
Recently, bedaquiline (acting as mycobacterial ATP synthase inhibitor with a high selectivity index) was approved for the treatment of drug-resistant TB cases.1 This discovery resulted in an increased interest to identify additional mycobacterial ATP synthase inhibitors. In 2017, Subramanyam et. al. identified very specific and selective squaramide lead exhibiting nanomolar antitubercular activity. Based on this knowledge we designed and synthesized modified squaramides and tested them for their biological properties. Some of the tested compounds showed interesting MIC values with low in vitro cytotoxicity.
Abstrakt anglicky: Tuberculosis (TB), an infectious disease predominantly caused by the bacillus Mycobacterium tuberculosis (Mtb) still poses a major and enduring global health threat. The infectious disease remains one of the top 10 causes of death and the leading cause of death due to a single infectious agent. In 2017, approximately 10 million people developed active TB disease and over 1.6 million persons died as a result. Furthermore, the epidemic is fuelled by the ever-increasing emergence of anti-TB drug resistance. Without a doubt, the discovery of entirely new compounds with an alternative mechanism of action to the existing therapeutics and directed towards unknown targets of Mtb becomes more and more desirable.
Recently, bedaquiline (acting as mycobacterial ATP synthase inhibitor with a high selectivity index) was approved for the treatment of drug-resistant TB cases.1 This discovery resulted in an increased interest to identify additional mycobacterial ATP synthase inhibitors. In 2017, Subramanyam et. al. identified very specific and selective squaramide lead exhibiting nanomolar antitubercular activity. Based on this knowledge we designed and synthesized modified squaramides and tested them for their biological properties. Some of the tested compounds showed interesting MIC values with low in vitro cytotoxicity.
Jazyk v originále: angličtina
Publikace abstraktu: sborník, 46
Forma prezentace: přednáška
Název konference: Liblice 2019
Místo konání: Špindlerův Mlýn
Datum konání: november 6 – 8
Rok konání: 2019
Způsob financování: JG_2019_002