Structurally diverse indole-3-pyrazole-5-carboxamide analogues (10-29) were designed,
synthesized, and evaluated for their antiproliferative activity against three cancer cell lines
(Huh7, MCF-7, and HCT116) using the sulforhodamine B assay. Some of the derivatives
showed anticancer activities equal to or better than sorafenib against cancer cell lines.
Compounds 18 showed potent activity against the hepatocellular cancer (HCC) cell lines, with
IC50 values in the range 0.6-2.9 μM. Compound 18 also exhibited moderate inhibitory activity
against tubulin polymerization (IC50 = 19 μM). Flow cytometric analysis of cultured cells treated
with 18 also demonstrated that the compound caused cell cycle arrest at the G2/M phase in both
Huh7 and Mahlavu cells and induced apoptotic cell death in HCC cells. Docking simulations
were performed to determine possible modes of interaction between 18 and the colchicine site of
tubulin and quantum mechanical calculations were performed to observe the electronic nature of
18 and to support docking results.

العنوان

Journal of Molecular Structure

الناشر

Elsevier

بلد الناشر

هولندا

Indexing

Thomson Reuters

معامل التأثير

3,8

نوع المنشور

Both (Printed and Online)

المجلد

1285

السنة

2023

الصفحات

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