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Organic Chemistry 2018 Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123 Page 22
August 16-17, 2018
Dublin, Ireland
6th Edition of International
Conference and Exhibition on
Organic Chemistry
T he cytotoxic effects of chemotherapy and radiation that
are clinically used to treat malignances are directly related
to their propensity to generate DNA damage. The capacity of
cancer cells to recognize DNA damage and initiate DNA repair is
a key mechanism for therapeutic resistance to chemotherapy.
Therefore, the targeting of DNA repair enzymes can be used
as a strategy to potentiate the cytotoxicity of the currently
available DNA damaging agents towards cancer cells. PARP1
(poly ADP ribose polymerase 1, the enzyme involved in DNA
repair) inhibitors such as Olaparib, Rucaparib and Niraparib
are in clinical use already. New and very promising target for
antitumor therapy is tyrosyl-DNA phosphodiesterase 1 (Tdp1).
It plays a key role in the removal of DNA damage resulting from
inhibition of topoisomerase 1 (Topo1) with camptothecin and
its clinical derivatives irinotecan and topotecan. Furthermore,
Tdp1 is known to be capable of removing the DNA damage
induced by other anticancer drugs commonly used in clinical
practice. To date, a number of Tdp1 inhibitors of various
types including dual Tdp1/Topo1 inhibitors are known. A set
of very potent Tdp1 inhibitors was found by us among natural
products derivatives. We designed new inhibitors using
targeted modifications of terpenoids, coumarins, usnic acid
and other types of natural products. Moreover, we found that
benzopentathiepine derivatives are very effective inhibitors of
Tdp1. Important that the ability of the inhibitors used in non-
toxic concentration to enhance the cytotoxicity of camptothecin
and topotecan, the established topoisomerase 1 poison, was
demonstrated. Thus, we discovered of new original Tdp1
inhibitors, effectively inhibiting DNA repair in tumor cells for
use as the components of complex anticancer drugs.
Biography
Konstantin Volcho pursued his PhD in 1997 from Novosibirsk State Univer-
sity, Russia. Since then he has been working in the department of medicinal
chemistry at Novosibirsk Institute of Organic Chemistry (Russia). He is a
Professor of Russian Academy of Sciences. His research interests include
development of novel treatments against nervous system disorders, antivi-
rals and anticancer agents, usually based on natural products derivatization.
He has published about 150 papers in reputed journals. He is an inventor in
more than 35 issued patents. Three compounds found with his participa-
tion are currently in preclinical studies as anti-parkinsonian, analgesic and
antidepressant agents.
DNA repair enzymes inhibition as a promising approach to
new anti-cancer drugs
Konstantin Volcho 1,2
1N N Vorozhtsov Novosibirsk Institute of Organic Chemistry RAS, Russia
2Novosibirsk State University, Russia
Konstantin Volcho, J Org Inorg Chem 2018, Volume 4
DOI: 10.21767/2472-1123-C4-011