Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties

Kovaleva, Kseniya S.; Yarovaya, Оlga I.; Ponomarev, Konstantin; Чересиз, С. В.; Azimirad, Amirhossein; Chernyshova, Irina; Zakharenko, Alexandra L.; Konev, Vasily; Khlebnikova, T. B.; Mozhaytsev, Evgenii S.; Суслов, Е. В.; Nilov, Dmitry K.; Švedas, Vytas K.; Pokrovsky, Andrey G.; Lavrik, Olga I.; Салахутдинов, Н. Ф.

doi:10.3390/ph14050422

Cited by 11 publications

(11 citation statements)

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“…Synthesized abiethylamine derivatives with an adamantyl urea substituent inhibit TDP1 at micromolar concentrations (IC 50 = 0.19–2.3 μM) [ 87 ]. Adamantane derivatives of resin acids 58 ( Figure 16 ) showed moderate toxicity to T98G cells (glioblastoma).…”

Section: Types Of Natural Compounds and Their Derivatives As Inhibito...mentioning

confidence: 99%

Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

Zakharenko

Luzina

Chepanova

et al. 2023

IJMS

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Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an important repair enzyme that removes various covalent adducts from the 3′ end of DNA. Particularly, covalent complexes of topoisomerase 1 (TOP1) with DNA stabilized by DNA damage or by various chemical agents are an examples of such adducts. Anticancer drugs such as the TOP1 poisons topotecan and irinotecan are responsible for the stabilization of these complexes. TDP1 neutralizes the effect of these anticancer drugs, eliminating the DNA adducts. Therefore, the inhibition of TDP1 can sensitize tumor cells to the action of TOP1 poisons. This review contains information about methods for determining the TDP1 activity, as well as describing the inhibitors of these enzyme derivatives of natural biologically active substances, such as aminoglycosides, nucleosides, polyphenolic compounds, and terpenoids. Data on the efficiency of combined inhibition of TOP1 and TDP1 in vitro and in vivo are presented.

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Section: Types Of Natural Compounds and Their Derivatives As Inhibito...mentioning

confidence: 99%

Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

Zakharenko

Luzina

Chepanova

et al. 2023

IJMS

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“…Also, ionic liquids are important in medicinal chemistry; due to their biological properties they are used as disinfectants, antimicrobials, and anti-inflammatory and anti-cancer agents [ 2 ]. The development, amalgamation, and production of molecules with benefits for people are among the basic objectives of therapeutic natural chemistry [ 3 , 4 , 5 ]. Recent developments in combinatorial chemistry have made it possible to obtain chemical libraries based on desirable structures [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Antibacterial and Anticandidal Activity of the Nanostructural Composite of a Spirothiazolidine-Derivative Assembled on Silver Nanoparticles

Alshammari,

Azzam,

Alhar

et al. 2024

Molecules

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Our aims in this work are the preparation of an ionic liquid based on heterocyclic compounds with Ag nanoparticles and the investigation of its application as an antibacterial and anticandidal agent. These goals were achieved through the fabrication of an ionic liquid based on Ag nanoparticles with 5-Amino-3-(4-fluorophenyl)-N-hexadecyl-7-(4-methylphenyl)-2-H spiro[cyclohexane1,2’-[1,3]thiazolo [4,5-b]pyridine]-6-carbonitrile (P16). The nanostructure of the prepared ionic liquid was characterized using techniques such as FTIR, 1HNMR, 13CNMR, UV, SEM, and TEM. The biological activity of the prepared compound (P16) and its nanocomposites with Ag nanoparticles was tested using five clinical bacteria (Pseudomonas aeruginosa 249; Escherichia coli 141; Enterobacter cloacae 235; Staphylococcus epidermidis BC 161, and methicillin-resistant S. aureus 217), and three Candida species (Candida utilis ATCC 9255; C. tropicalis ATCC 1362, and C. albicans ATCC 20402). The FTIR, 1HNMR, and 13CNMR results confirmed the chemical structure of the synthesized P16 compound. The nanostructure of the prepared ionic liquid was determined based on data obtained from the UV, SEM, and TEM tests. The antibacterial and anticandidal results showed that the biological activity of the compound (P16) was enhanced after the formation of nanocomposite structures with Ag nanoparticles. Moreover, the biological activity of the compound itself (P16) and that of its nanocomposite structure with Ag nanoparticles was higher than that of ampicillin and amphotericin B, which were used as control drugs in this work.

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“…Compounds that combine pharmacophore fragments of natural and synthetic origin also performed well, including resin acid derivatives 7 [ 10 ], and terpenoadamantanes 8 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties

Ivankin

Kornienko

Mikhailova

et al. 2023

IJMS

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Tyrosyl-DNA-phosphodiesterase 1 (TDP1) is a promising target for antitumor therapy; the use of TDP1 inhibitors with a topoisomerase 1 poison such as topotecan is a potential combination therapy. In this work, a novel series of 3,5-disubstituted thiazolidine-2,4-diones was synthesized and tested against TDP1. The screening revealed some active compounds with IC50 values less than 5 μM. Interestingly, compounds 20d and 21d were the most active, with IC50 values in the submicromolar concentration range. None of the compounds showed cytotoxicity against HCT-116 (colon carcinoma) and MRC-5 (human lung fibroblasts) cell lines in the 1–100 μM concentration range. Finally, this class of compounds did not sensitize cancer cells to the cytotoxic effect of topotecan.

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Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties

Cited by 11 publications

References 50 publications

Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

Antibacterial and Anticandidal Activity of the Nanostructural Composite of a Spirothiazolidine-Derivative Assembled on Silver Nanoparticles

Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties

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