| Title |
Naujų imidazolo ir 1,2,3-tiadiazolo darinių, turinčių 1,3-benzendiolio fragmentą, sintezė šiluminio šoko baltymo Hsp90 slopiklių paieškai / |
| Translation of Title |
Synthesis of novel imidazole and 1,2,3-thiadiazole derivatives containing benzene-1,3-diol fragment for the development of inhibitors of heat shock protein Hsp90. |
| Authors |
Kaziukonytė, Paulina |
| DOI |
10.15388/vu.thesis.694 |
| Full Text |
|
| Pages |
131 |
| Keywords [eng] |
imidazole ; 1,2,3-thiadiazole ; Hsp90 |
| Abstract [eng] |
Not only does the heat shock protein Hsp90 ensure normal cell functions by regulating the activation and structure of other proteins, but it also participates in the development and stabilization of cancer proteins, making it a potent target for anticancer drug research. Thirty new imidazole and 1,2,3-thiadiazole derivatives containing a benzene-1,3-diol fragment were synthesized to determine inhibition activity for Hsp90 α and β isoforms. The findings indicate that thiadiazole derivatives bind to Hsp90 more effectively than imidazole compounds. However, the activity of the imidazole derivatives offers valuable insights into the influence of substituents on binding. Notably, isopropylresorcinol-imidazole derivatives with substituents such as 4-methylphenyl, 4-methoxyphenylmethyl, and cyclohexyl demonstrate significant activity, with some compounds interacting 2-4 times better with Hsp90α than with Hsp90β. Interestingly, modifying the 4-isopropyl group of resorcinol to a benzyl substituent further increased isoform selectivity to 8.3 times. During the van Leusen imidazole synthesis, the formation of a previously undescribed heterocyclic benzofuro[2,3-d]imidazole system was observed. It forms when 2-hydroxybenzaldehydes and anilines are used as starting compounds and the formation is enhanced by the use of protic solvents and strong inorganic bases. Semi-empirical calculations suggest that its formation follows an SN2 reaction mechanism. |
| Dissertation Institution |
Vilniaus universitetas. |
| Type |
Doctoral thesis |
| Language |
Lithuanian |
| Publication date |
2024 |
