Drug metabolism and bioanalysis letters · 2024
Analyzing Interaction of Rhodacyanine Inhibitor 'MKT-077' with Plasmodium falciparum HSP70s.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nainani Kumari Chanchal, Upadhyay Vipul, Singh Bikramjit, Sandhu Komalpreet Kaur, Kaur Satinder, Hora Rachna, Mishra Prakash Chandra
Аннотация
INTRODUCTION: MKT-077 and its derivatives are rhodacyanine inhibitors that hold potential in the treatment of cancer, neurodegenerative diseases and malaria. These allosteric drugs act by inhibiting the ATPase action of heat shock proteins of 70 kDa (HSP70). MKT-077 accumulates in the mitochondria and displays differential activity against HSP70 homologs.
METHODS: The four Plasmodium falciparum HSP70s (PfHSP70) are present in various subcellular locations to perform distinct functions. In the present study, we have used bioinformatics tools to understand the interaction of MKT-077 at the ADP and HEW (2-amino 4 bromopyridine) binding sites on PfHSP70s. Our molecular docking experiments predict that the mitochondrial and endoplasmic reticulum PfHSP70 homologs are likely to bind MKT-077 with higher affinities at their ADP binding sites.
RESULTS: Binding analysis indicates that the nature of the identified interactions is primarily hydrophobic. We have also identified specific residues of PfHSP70s that are involved in interacting with the ligand.
CONCLUSION: Information obtained in this study may form the foundation for the design and development of MKT-077-based drugs against malaria.
METHODS: The four Plasmodium falciparum HSP70s (PfHSP70) are present in various subcellular locations to perform distinct functions. In the present study, we have used bioinformatics tools to understand the interaction of MKT-077 at the ADP and HEW (2-amino 4 bromopyridine) binding sites on PfHSP70s. Our molecular docking experiments predict that the mitochondrial and endoplasmic reticulum PfHSP70 homologs are likely to bind MKT-077 with higher affinities at their ADP binding sites.
RESULTS: Binding analysis indicates that the nature of the identified interactions is primarily hydrophobic. We have also identified specific residues of PfHSP70s that are involved in interacting with the ligand.
CONCLUSION: Information obtained in this study may form the foundation for the design and development of MKT-077-based drugs against malaria.