Design, synthesis, and evaluation of dehydroabietyl imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones as TDP1 inhibitors and dual TDP1/TDP2 inhibitors.

Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.

GENETIC VARIANTS IN ANTIPSYCHOTIC METABOLISM: POLYMORPHISM PROFILES IN KAZAKH COHORT WITH PARANOID SCHIZOPHRENIA.

Schizophrenia is a multifaceted psychiatric disorder characterized by hallucinations, delusions, cognitive impairments, and behavioral disturbances. Genetic factors significantly contribute to its pathogenesis, accounting for approximately 80% of the heritability. Globally, about 1% of the population is affected by schizophrenia, with 45,054 individuals in Kazakhstan receiving medical treatment for the condition, indicating a prevalence rate of 238,6 per 100,000 people.

GENETIC ASSOCIATIONS WITH ASTHMA IN THE KAZAKH POPULATION: A CASE-CONTROL STUDY FOCUSING ON ACTN3 AND TSBP1 POLYMORPHISMS.

Background: Asthma is a prevalent chronic respiratory disease that significantly impacts the quality of life. Genetic factors, particularly single nucleotide polymorphisms (SNPs), play a crucial role in asthma susceptibility. This study investigates the genetic determinants associated with asthma in the Kazakh population, focusing on SNPs within the ACTN3 and TSBP1 genes.

The Reaction of Fenchone and Camphor Hydrazones with 5-Acyl-4-Pyrones as a Method for the Synthesis of New Polycarbonyl Conjugates: Tautomeric Equilibrium and Antiviral Activity.

Selective synthesis of polycarbonyl conjugates of (+)-fenchone and (+)-camphor was carried out (44-91 % yields) via the ring-opening transformation of 5-acyl-4-pyrones with hydrazones of the corresponding monoterpenoids. A strong influence of the hydrazone fragment on the observed tautomeric equilibrium of the tricarbonyl system was shown. Although the major tautomer of the conjugates is the acyclic polycarbonyl form, the camphor-based conjugates undergo new type of ring-chain tautomerism, diketoenaminone-dihydropyridone equilibrium, and predominantly exist in the cyclic dihydropyridone form in DMSO-d.

Development of an LC-MS/MS-based method for quantification and pharmacokinetics study on SCID mice of a dehydroabietylamine-adamantylamine conjugate, a promising inhibitor of the DNA repair enzyme.

Earlier, it was found that the agent KS-389, a conjugate of dehydroabietylamine and 1-aminoadamantane, possess inhibiting activity with regard to Tdp1. It this study, LC-MS/MS-based methods of quantification of KS-389 in mice blood and several organs (brain, liver and kidney) were developed and validated. Validation of the methods was performed according to the guidelines of U.