Pokorny, Jan published the artcileSubstituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters, Application In Synthesis of 76283-09-5, the publication is European Journal of Medicinal Chemistry (2021), 113706, database is CAplus and MEDLINE.
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Four compounds had IC50 below 5μmol/L; I and II were selected for studies of the mechanism of action. Cell cycle anal. revealed an increase in the number of apoptotic cells at 5 x IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both I and II led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 x IC50 and almost complete inhibition at 5 x IC50. Interestingly, compound II at 5 x IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds I and II trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacol. parameters of derivative I were superior to II, therefore I was the finally selected candidate for the development of anticancer drug.
European Journal of Medicinal Chemistry published new progress about 76283-09-5. 76283-09-5 belongs to bromides-buliding-blocks, auxiliary class Fluoride,Bromide,Benzyl bromide,Benzene, name is 4-Bromo-1-(bromomethyl)-2-fluorobenzene, and the molecular formula is C7H5Br2F, Application In Synthesis of 76283-09-5.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary