Синтезирован аналог соматостатина, обладающий гормональной и противоопухолевой активностью. Разработан оптимальный метод синтеза, позволяющий получать стандартную фармацевтическую субстанцию аналога соматостатина для доклинических и клинических исследований. Разработаны методики контроля качества, которые будут включены в проект ФСП на фармацевтическую субстанцию аналога соматостатина.
Взаимодействием N-гликозидов индоло[2,3-a]фурано[3,4-c]карбазол-5,7-дионов с гидразингидратом, гидрохлоридом гидроксиламина, формилгидразином получены соответствующие N-6 замещенные гликозиды индолопирролокарбазолов. В качестве углеводных остатков использованы L-арабиноза, D-галактоза, D-ксилоза и D-рибоза. Полученные соединения изучены in vitro и in vivo. Они показали значительную антипролиферативную активность на клетках HCT-116 (IC50 10–6 – 10–7 М) и высокий противоопухолевый эффект на асцитных моделях опухоли Эрлиха и лимфолезкозе Р-388. Увеличение продолжительности жизни животных на первой модели составило от 540 – 495 % до 172 – 132 % и от 80 – 83 % до 120 – 93 % на второй модели.
Introduction. Quantitative assessment of the active substance is necessary and perhaps the most significant part of the drug quality control. Validation of the analytical methods of quantitative assessment ensures their compliance with high requirements. The present study describes the development and validation of a spectrophotometry method for the quantitative evaluation of the active substance in the drug form of the national antitumor and antiangiogenic drug «Dimeric macrocyclic tannin (DMT) lyophilizate for solution for injection, 100 mg».Aim. The development and validation of the assay method for the standardization of «DMT lyophilizate for solution for injection, 100 mg».Materials and metods. The study used «DMT lyophilizate for solution for injection, 100 mg» and the active substance DMT. Method – spectrophotometry.Results and discussion. The methodof the quantitative assessment of the active substance in the DMT lyophilized drug by direct UV spectrophotometry was developed and the validation characteristics of the method were defined as a result of the study.Conclusion. The validation results showed that the assay method of DMT in the drug form has the appropriate accuracy, precision and linearity. The obtained results correspond to the approved criteria that allow the use of the developed methodology for evaluating the quality of the drug.
Приведены результаты валидации методики количественного спектрофотометрического определения ормустина в лиофилизированной лекарственной форме. Показано, что методика пригодна для определения количественного содержания ормустин по параметрам: специфичность, линейность, правильность, сходимость и внутрилабораторная прецизионность.
1-(2,3,5-Tri-O-acetyl)-beta-D-ribofuranosyl indole, the key compound in the synthesis of glycosides with the bis(indole) aglycone, was obtained for the first time by the indoline-indole method. There were synthesized 3-(1-methylindol-3-yl)-4-(1-glycosylindol-3-yl)furan(or pyrrole)-2,5-diones containing the residue of beta-D-ribofuranose or 2-deoxy-beta-D-ribofuranose and analogous glycosides of indolo[2,3-a]furano(or pyrrolo)[3,4-c]carbazol-5,7-diones, which are structurally relative to the antitumor antibiotic rebeccamycin. Their cytotoxicities toward a number of human tumor cell lines were studied in vitro, and the carbazole N-glycosides were shown to be more active than the bis-(indole) glycosides. At the same time, the ribofuranosides were found to be less active than the corresponding ribopyranosides synthesized previously.
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