Исследование методом сетевой фармакологии и молекулярного докинга для выявления потенциальной противораковой активности морских цитотоксинов — осциллатоксинов D, E, и F

Осциллатоксины (OTXs) —  это цитотоксины, продуцируемые некоторыми морскими цианобактериями. Их уникальные структуры показывают высокую эффективность в качестве противораковых средств. Ограниченная доступность производных OTXs в природе дает мало информации об их биологической активности. Было тестировано несколько активностей OTXs в исследованиях in vitro или in vivo в отношении линий раковых клеток, но их точный механизм действия на мишень не ясен. В данном исследовании мы использовали метод сетевой фармакологии для прогнозирования мишеней и механизмов действия осциллатоксина D (OTX-D), 30 метил-осциллатоксина D (30-метил-OTX-D), осциллатоксина E (OTX-E), и осциллатоксина F (OTX-F). Существуют 20 возможных мишеней четырех соединений против рака и их основными мишенями являются PIK3CA, CDK1 и MTOR. Затем было проведено исследование методом молекулярного докинга для понимания взаимодействия между 4 соединениями и их мишенями. Молекулярный докинг показал, что 4 соединения хорошо взаимодействовали с ключевыми мишенями. В данной работе было выявлено 4 производных OTXs и 3 ключевых мишени для противоракового действия, указывая на множественные сигнальные пути, включая путь экспрессии PD-L1 и контрольной точки PD-1 при раке, протеогликаны при раке и пути при раке, устанавливая теоретические рамки для дальнейшего экспериментального исследования.

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