Autor: Chasák, J.; Berka, K.; Bazgier, V.; Cappoen, D.; Brulíková, L.
Název práce v češtině: Deriváty kyseliny squarové jako potenciální antituberkulotika
Název práce v angličtině: Squaric acid derivatives as new potential antituberculosis agents
Klíčová slova v češtině: tuberkulóza,squaramidy, ATP synthasa
Klíčová slova v angličtině:tuberculosis, squaramides, ATP synthases
Abstrakt česky: Mycobacterium tuberculosis je pathogenní bakterie způsobující tuberkulózu. Toto onemocnění ročně zabíjí přibližně 1,5 milionu lidí. proto je třeba vyvíjet nová léčiva, která by působila novým mechanismem. Jeden ze slibných cílů je mykobakteriální ATP synthasa. V naší skupině připravujeme látky založené na struktuře squaramidu cílících právě na mykobakteriální ATP syntahsu.
Abstrakt anglicky: Mycobacterium tuberculosis is a pathogenic bacteria and causative agent of tuberculosis (TB). Although tuberculosis has been almost eradicated on the European continent in the past, it is currently a serious health problem worldwide causing approximately 1.3–1.5 million deaths every year. Therefore, new unexplored chemical scaffolds with antimycobacterial activity and new mechanisms of action are desired. One of the most popular molecular targets is currently mycobacterial ATP synthase, inhibitors of which began to be massively developed after the approval of bedaquiline.
After recent work published by Tantry et al. in 2017, we started to deal with squaramides, derivatives of squaric acid 1, as potential inhibitors of mycobacterial ATP synthase. Initially, two series of squaramides were proposed – amine 2 and aryl 3 derivatives. The results of biological testing suggest that the aryl ones are far more active that amine derivatives 2 . Based on this, we have designed a rather extensive library of variously substituted aryl squaramides. Some of them were successfully prepared by already published synthetic methodology using Friedel-Crafts reaction as a key step in forming a new C-C bond. Nevertheless, for some suggested derivatives, it was necessary to open up and optimize an entirelynew synthetic approach in which the Friedel-Crafts reaction is replaced by Liebeskind-Srogl coupling. All prepared derivatives were tested for their biological properties. Some tested compounds exhibit interesting MIC values with low in vitro cytotoxicity.
Jazyk v originále: angličtina
Publikace abstraktu: sborník, P44
Forma prezentace: poster
Název konference: Liblice 2022
Místo konání: Špindlerův mlýn
Datum konání: November 10 – 12
Rok konání: 2022
Způsob financování: JG_2019_002 , IGA_PrF_2021_024, IGA_PrF_2022_022