19894-97-4Relevant articles and documents
New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7-hydroxycoumarin and monoterpenoid moieties
Khomenko, Tatyana,Zakharenko, Alexandra,Odarchenko, Tatyana,Arabshahi, Homayon John,Sannikova, Victoriya,Zakharova, Olga,Korchagina, Dina,Reynisson, Jóhannes,Volcho, Konstantin,Salakhutdinov, Nariman,Lavrik, Olga
, p. 5573 - 5581 (2016)
A number of derivatives of 7-hydroxycoumarins containing aromatic or monoterpene substituents at hydroxy-group were synthesized based on a hit compound from a virtual screen. The ability of these compounds to inhibit tyrosyl-DNA phosphodiesterase I (Tdp 1), important target for anti-cancer therapy, was studied for the first time. It was found that the 7-hydroxycoumarin derivatives with monoterpene pinene moiety are effective inhibitors of Tdp 1 with the most active derivative (+)-25c with IC50value of 0.675?μM. This compound has low cytotoxicity (CC50?>100?μM) when tested against human cancer cells which is crucial for presupposed application in combination with clinically established anticancer drugs. The ability of the new compounds to enhance the cytotoxicity of camptothecin, an established topoisomerase 1 poison, was demonstrated.
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Zweifel,G.,Whitney,C.C.
, p. 4178 - 4180 (1966)
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New hybrid compounds combining fragments of usnic acid and monoterpenoids for effective tyrosyl-dna phosphodiesterase 1 inhibition
Dyrkheeva, Nadezhda S.,Filimonov, Aleksandr S.,Luzina, Olga A.,Zakharenko, Alexandra L.,Ilina, Ekaterina S.,Malakhova, Anastasia A.,Medvedev, Sergey P.,Reynisson, Jóhannes,Volcho, Konstantin P.,Zakian, Suren M.,Salakhutdinov, Nariman F.,Lavrik, Olga I.
, (2021/07/02)
Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabi-lized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cyto-toxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protec-tive” effect from topotecan on non-cancerous cells requires further investigation.
Deep eutectic solvents as H2-sources for Ru(II)-catalyzed transfer hydrogenation of carbonyl compounds under mild conditions
Cavallo, Marzia,Arnodo, Davide,Mannu, Alberto,Blangetti, Marco,Prandi, Cristina,Baratta, Walter,Baldino, Salvatore
supporting information, (2021/02/22)
The employment of easily affordable ruthenium(II)-complexes as pre-catalysts in the transfer hydrogenation of carbonyl compounds in deep eutectic media is described for the first time. The eutectic mixture tetrabutylammonium bromide/formic acid = 1/1 (TBABr/HCOOH = 1/1) acts both as reaction medium and hydrogen source. The addition of a base is required for the process to occur. An extensive optimization of the reaction conditions has been carried out, in terms of catalyst loading, type of complexes, H2-donors, reaction temperature and time. The combination of the dimeric complex [RuCl(p-cymene)-μ-Cl]2 (0.01–0.05 eq.) and the ligand dppf (1,1′-ferrocenediyl-bis(diphenylphosphine)ferrocene) in 1/1 molar ratio has proven to be a suitable catalytic system for the reduction of several and diverse aldehydes and ketones to their corresponding alcohols under mild conditions (40–60 °C) in air, showing from moderate to excellent tolerability towards different functional groups (halogen, cyano, nitro, phenol). The reduction of imine compounds to their corresponding amine derivatives was also studied. In addition, the comparison between the results obtained in TBABr/HCOOH and in organic solvents suggests a non-innocent effect of the DES medium during the process.
