Two undescribed alkaloids
(10 and 11),
along with nine known alkaloids (1–9), have been
isolated from the stem and root bark of Glycosmis pentaphylla. Among them are carbocristine (11), a carbazole alkaloid
first time isolated from a natural source, and acridocristine (10), a pyranoacridone alkaloid first time isolated from the
genus “Glycosmis”. In vitro cytotoxicity of isolated compounds has been analyzed
on breast cancer (MCF-7), lung cancer (CALU-3), and squamous cell
carcinoma cell lines (SCC-25). The results demonstrated that compounds
are moderately active. In order to study the structural activity relationship
of majorly isolated compounds, semisynthetic modifications have been
done on majorly isolated compounds such as des-N-methylacronycine
(4) and noracronycine (1) to synthesize
11 semisynthetic derivatives (12–22) on functionalizable −NH and −OH groups of the pyranoacridone
scaffold at 12th and 6th positions. Semisynthetic derivatives are
explored on the same cell lines as isolated compounds, and the results
exhibit that semisynthetic compounds showed potent cytotoxic activity
compared with naturally isolated compounds. In the case of CALU-3,
the dimer at −OH position of noracronycine (1),
i.e., compound 22, showed 24-fold better activity with
an IC50 of 4.49 μM compared with noracronycine (1) with IC50 97.5 μM. In MCF-7, the dimer
at −OH position of noracronycine (1), i.e., compound 22, showed 14-fold better activity with an IC50 of 13.2 μM compared with noracronycine (1) with
IC50 187 μM.
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