| Summary: | This study represents the design and synthesis of a new set of hybrid and chimeric derivatives of 4,5-dihydro-4,4-dimethyl-1<i>H</i>-[1,2]dithiolo[3,4-<i>c</i>]quinoline-1-thiones, the structure of which the tricyclic fragment linearly bound or/and condensed with another heterocyclic fragment. Using the PASS Online software, among the previously synthesized and new derivatives of 1,2-dithiolo[3,4-<i>c</i>]quinoline-1-thione we identified 12 substances with pleiotropic activity, including chemoprotective and antitumor activity. All the synthesized derivatives were screened for their inhibitory assessment against a number of kinases. Compounds which exhibited prominent inhibition percentage in cells (>85%) were also examined for their inhibitory efficiency on human kinases via ELISA utilizing sorafenib as a reference standard to estimate their IC<sub>50</sub> values. It was revealed that compounds <b>2a</b>, <b>2b</b>, <b>2c</b>, and <b>2q</b> displayed a significant inhibition JAK3 (IC<sub>50</sub> = 0.36 μM, 0.38 μM, 0.41 μM, and 0.46 μM, respectively); moreover, compounds <b>2a</b> and <b>2b</b> displayed excellent activities against NPM1-ALK (IC<sub>50</sub> = 0.54 μM, 0.25 μM, respectively), against cRAF[Y340D][Y341D], compound <b>2c</b> showed excellent activity, and compound <b>2q</b> showed weak activity (IC<sub>50</sub> = 0.78 μM, 5.34 μM, respectively) (sorafenib IC<sub>50</sub> = 0.78 μM, 0.43 μM, 1.95 μM, respectively). Thus, new promising preferred structures for the creation of drugs for the treatment of cancer and other multifactorial diseases in the future have been found.
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