Реферат: Inhibiting tyrosyl-DNA phosphodiesterase 1 (TDP1) is a promising strategy for increasing the effectiveness of existing antitumor therapy since it can remove the DNA lesions caused by anticancer drugs, which form covalent complexes with topoisomerase 1 (TOP1). Here, new adamantane–monoterpene conjugates with a 1,2,4-triazole or 1,3,4-thiadiazole linker core were synthesized, where (+)-and (−)-campholenic and (+)-camphor derivatives were used as monoterpene fragments. The campholenic derivatives 14a–14b and 15a–b showed activity against TDP1 at a low micromolar range with IC50 ~5–6 μM, whereas camphor-containing compounds 16 and 17 were ineffective. Surprisingly, all the compounds synthesized demonstrated a clear synergy with topotecan, a TOP1 poison, regardless of their ability to inhibit TDP1. These findings imply that different pathways of enhancing topotecan toxicity other than the inhibition of TDP1 can be realized.

Библиографическая ссылка: Munkuev A.A. , Dyrkheeva N.S. , Kornienko T.E. , Ilina E.S. , Ivankin D.I. , Suslov E.V. , Korchagina D.V. , Gatilov Y.V. , Zakharenko A.L. , Malakhova A.A. , Reynisson J. , Volcho K.P. , Salakhutdinov N.F. , Lavrik O.I.
Adamantane-Monoterpenoid Conjugates Linked via Heterocyclic Linkers Enhance the Cytotoxic Effect of Topotecan
Molecules. 2022. V.27. N11. P.3374. DOI: 10.3390/molecules27113374 WOS Scopus РИНЦ

Даты:

Поступила в редакцию:	29 апр. 2022 г.
Опубликована online:	24 мая 2022 г.

Идентификаторы:

Web of science	WOS:000809087000001
Scopus	2-s2.0-85131621603
РИНЦ	49149577
OpenAlex	W4281477670

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