Herein, we synthesized a new series of imidazolone derivatives 4a–4i and assessed their anticancer
activities against liver cancer cells (Hep3B), Hela cells, and normal LX2 cells. The imidazolne
derivatives were synthesized by the condensation cyclization reaction using the natural product
vanillin as a starting material. Among the synthesized imidazolones are those with an alkyl sulfate
moiety that are water-soluble and showed enhanced anticancer activity against the tested cancer
cells. The anticancer testing results showed that compound 4d with the NO2 group at position 4 of
the benzene ring was superior to the other compounds; it showed an IC50 value of 134.2  4.4 M
against Hep3B cells, while compound 4h with the pyridyl moiety showed the highest cytotoxicity
against Hela cells with an IC50 of 85.1  2.1 M. The anticancer activity of some imidazolones was
greatly enhanced by adding to them the zwitterionic properties that made them more polar and
water-soluble. DNA binding studies with compounds 4a1, 4d, and 4g indicated a docking score
ranging from approximately ????6.8 to ????8.7 kcal/mol. This could be attributed to the outstanding
interaction between the molecule and the DNA binding sites, which primarily relies on its inherent
capability to establish hydrogen bonds, facilitated by the electron pair present at the oxygen atoms
and the drug’s amino group. In conclusion, water-soluble imidazolone with zwitterionic functionality
could be a promising tool for the development of anticancer medication. To outline the general
idea and the relationships for the effect of the developed compounds under study, as well as their
mechanism of action, further extensive research is also necessary.

Title

Chemistry

Publisher

MDPI

Publisher Country

Switzerland

Indexing

Scopus

Impact Factor

2.5

Publication Type

Prtinted only

Volume

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Year

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Pages

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