HETEROCYCLIC ANALOGS OF 5,12-NAPHTHACENEQUINONE 16*. SYNTHESIS AND PROPERTIES OF NEW DNA LIGANDS BASED ON 4,11-DIAMINOANTHRA[2,3-<i>b</i>]THIOPHENE-5,10-DIONE

Authors

  • Дарья B. Андреева Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia
  • Александр С. Тихомиров Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow 125190, Russia
  • Любовь Г. Деженкова Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia
  • Дмитрий Н. Калюжный Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilova St., Moscow 119991, Russia
  • Ольга К. Мамаева Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilova St., Moscow 119991, Russia
  • Светлана Е. Соловьева Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia
  • Юрий Б. Синькевич Российский химико-технологический университет им. Д. И. Менделеева, Миусская пл., 9, Москва 125190, Россия
  • Андрей Е. Щекотихин Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow 125190, Russia

DOI:

https://doi.org/10.1007/5606

Keywords:

anthra[2, 3-b]thiophene-5, 10-diones, nucleic acids, antitumor properties, G-quadruplexes, nucleophilic substitution.

Abstract

A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the
introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth,
which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.

Author Biography

Александр С. Тихомиров, Gause Institute of New Antibiotics, 11 B. Pirogovskaya St., Moscow 119021, Russia Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow 125190, Russia

Старший научный сотрудник Лаборатории химической трансформации антибиотиков НИИ по изысканию новых антибиотиков

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Published

2020-07-10

Issue

Vol. 56 No. 6 (2020): Heterocyclic сompounds in medicinal chemistry

Section

Original Papers