65068-86-2Relevant academic research and scientific papers
Design, synthesis, and molecular docking study of new tyrosyl-dna phosphodiesterase 1 (Tdp1) inhibitors combining resin acids and adamantane moieties
Kovaleva, Kseniya,Yarovaya, Olga,Ponomarev, Konstantin,Cheresiz, Sergey,Azimirad, Amirhossein,Chernyshova, Irina,Zakharenko, Alexandra,Konev, Vasily,Khlebnikova, Tatiana,Mozhaytsev, Evgenii,Suslov, Evgenii,Nilov, Dmitry,?vedas, Vytas,Pokrovsky, Andrey,Lavrik, Olga,Salakhutdinov, Nariman
, (2021/05/22)
In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their in-hibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19–2.3 μM) and demonstrated low cytotox-icity in the T98G glioma cell line. The effect of the terpene fragment, the linker structure, and the adamantane residue on the biological properties of the new compounds was investigated. Based on molecular docking results, we suppose that adamantane derivatives of resin acids bind to the TDP1 covalent intermediate, forming a hydrogen bond with Ser463 and hydrophobic contacts with the Phe259 and Trp590 residues and the oligonucleotide fragment of the substrate.
Adamantyl Isothiocyanates as Mutant p53 Rescuing Agents and Their Structure-Activity Relationships
Burmistrov, Vladimir,Saxena, Rahul,Pitushkin, Dmitry,Butov, Gennady M.,Chung, Fung-Lung,Aggarwal, Monika
supporting information, p. 6621 - 6633 (2021/05/29)
Mutant p53 rescue by small molecules is a promising therapeutic strategy. In this structure-activity relationship study, we examined a series of adamantyl isothiocyanates (Ad-ITCs) to discover novel agents as therapeutics by targeting mutant p53. We demonstrated that the alkyl chain connecting adamantane and ITC is a crucial determinant for Ad-ITC inhibitory potency. Ad-ITC 6 with the longest chain between ITC and adamantane displayed the maximum growth inhibition in p53R280K, p53R273H, or p53R306Stop mutant cells. Ad-ITC 6 acted in a mutant p53-dependent manner. It rescued p53R280K and p53R273H mutants, thereby resulting in upregulating canonical wild-type (WT) p53 targets and phosphorylating ATM. Ad-ISeC 14 with selenium showed a significantly enhanced inhibitory potency, without affecting its ability to rescue mutant p53. Ad-ITCs selectively depleted mutant p53, but not the WT, and this activity correlates with their inhibitory potencies. These data suggest that Ad-ITCs may serve as novel promising leads for the p53-targeted drug development.
Synthesis of Homologs of 1-Isothiocyanatoadamantane
Pitushkin,Burmistrov,Butov
, p. 1475 - 1479 (2019/01/04)
Amines of the adamantane series reacted with carbon disulfide and di-tert-butyl dicarbonate in the presence of triethylamine and a catalytic amount of 4-(dimethylamino)pyridine to give homologs of 1-isothiocyanatoadamantane in 80–86% yields. Adamantan-2-a
Nitrogen heterocyclic carboximidamide compounds
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, (2008/06/13)
5-, 6- or 7-Membered fully saturated 1-azacarbocyclic-2-ylidene derivatives of guanidine having anti-secretory and hypoglycemic activities, and further useful for treatment of cardiovascular disease states.
