Open AccessN-glycosidesindolo[2,3,-a]pyrrolo[3,4,-c]carbazole derivatives chemical structure influence on antitumor activity
Author(s) -
М. П. Киселева,
В. С. Покровский,
Л. М. Борисова,
И. С. Голубева,
Л. В. Эктова
Publication year - 2019
Publication title -
rossijskij bioterapevtičeskij žurnal
Language(s) - English
Resource type - Journals
eISSN - 1726-9792
pISSN - 1726-9784
DOI - 10.17650/1726-9784-2019-18-2-32-39
Subject(s) - lewis lung carcinoma , christian ministry , chemistry , carbazole , glycoside , stereochemistry , melanoma , epidermoid carcinoma , rational design , lung cancer , chemical structure , cancer research , carcinoma , cancer , oncology , organic chemistry , medicine , metastasis , nanotechnology , materials science , philosophy , theology
. The report considers the prospect of rational approach to the new anticancer agents creation based on indolocarbazole derivatives. Objective . To conduct a comparative study of 12 domestic N-glycosides, indolo[2,3-a]pirrolo[2,3-a]carbazole derivatives in the course of “structure – activity” bond analysis. Materials and methods . The investigation of influence of 12 carbohydrate – containing indolocarbazoles, synthesized in N. N. Blokhin Russian Cancer Research Center of the Ministry of Health of Russia, performed on models of solid transplantable mouse tumors: lung Lewis epidermoid carcinoma and B16 melanoma. The antitumor effect was assessed by Lewis epidermoid carcinoma and B16 melanoma tumor growth inhibition (TGI %) criterion. Results . A variety of indolocarbazoles modifications allowed revealing the dependence of their antitumor properties on the structure of both, the aglycone and the glycoside residue. Imino-nitrogen interchange of atoms in upper heterocycle influences on indocarbazole derivatives antitumor activity change. During a comparative study of 12 N-glycosides indolocarbazole derivatives on lung Lewis epidermoid carcinoma and B16 melanoma models, 8 derivatives showed antitumor activity. Conclusion . The formulated concepts on the modification features in indolocarbazole derivatives structure can be used for more active compounds creation with greater action selectivity.