Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F21%3A43923117" target="_blank" >RIV/60461373:22330/21:43923117 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2072-6694/13/18/4563" target="_blank" >https://www.mdpi.com/2072-6694/13/18/4563</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13184563" target="_blank" >10.3390/cancers13184563</a>

Result language

angličtina

Original language name

Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers

Original language description

The search for novel anticancer agents has been the hot topic of interest in cancer research, due to the phenomenon of multidrug resistance (MDR) in cancer that can make cancer cells resistant to the current available chemotherapeutic agents. In this context, we have designed, synthesized, and biologically evaluated 15 novel selenoesters, with the aim to explore their activity against resistant cancer cell lines. Some of these described selenocompounds showed noteworthy cytotoxicity and selectivity, the ability to inhibit the ABCB1 efflux pump, the capacity to modulate the ATPase activity of this pump, the capability to trigger apoptotic events, the ability to interact in a synergistic manner with doxorubicin in resistant cancer cells, and the power to promote wound healing. Consequently, these results validate the design of these selenocompounds and justify further research to evaluate the possibilities of these compounds to be used in the future in the fight against resistant cancers. Fifteen selenocompounds, comprising of eight ketone-containing selenoesters (K1-K8, also known as oxoselenoesters) and seven cyano-containing selenoesters (N1-N7, known also as cyanoselenoesters), have been designed, synthesized, and evaluated as novel anticancer agents. These compounds are derivatives of previously reported active selenoesters and were prepared following a three-step one-pot synthetic route. The following evaluations were performed in their biological assessment: cytotoxicity determination, selectivity towards cancer cells in respect to non-cancer cells, checkerboard combination assay, ABCB1 inhibition and inhibition of ABCB1 ATPase activity, apoptosis induction, and wound healing assay. As key results, all the compounds showed cytotoxicity against cancer cells at low micromolar concentrations, with cyanoselenoesters being strongly selective. All of the oxoselenoesters, except K4, were potent ABCB1 inhibitors, and two of them, namely K5 and K6, enhanced the activity of doxorubicin in a synergistic manner. The majority of these ketone derivatives modulated the ATPase activity, showed wound healing activity, and induced apoptosis, with K3 being the most potent, with a potency close to that of the reference compound. To summarize, these novel derivatives have promising multi-target activity, and are worthy to be studied more in-depth in future works to gain a greater understanding of their potential applications against cancer.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/LTC19007" target="_blank" >LTC19007: Testing of the new compounds with potential for resistance modulation in multi drug resistant strains</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

18

Country of publishing house

CH - SWITZERLAND

Number of pages

26

Pages from-to

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UT code for WoS article

000699317100001

EID of the result in the Scopus database

2-s2.0-85114644415