New Isatin–Indole Conjugates: Synthesis, Characterization, and a Plausible Mechanism of Their in vitro Antiproliferative Activity

Journal Article

2020

Cancer remains the leading cause of human morbidity universally. Hence, we
sought to assess the in vitro antiproliferative activity of new isatin-based conjugates (5a–s)
against three human cancer cell lines.
The in vitro antiproliferative activities of compounds 5a–s against the tested cancer cell
lines ranged from 20.3 to 95.9%. Compound 5m had an IC50 value of 1.17 µM; thus, its
antiproliferative potency was approximately seven-fold greater than that of sunitinib (IC50 =
8.11 µM). In-depth pharmacological testing was conducted with compound 5m to gain insight
into the potential antiproliferative mechanism of this class of compounds. Compound 5m caused
an increase in the number of cells in the G1 phase, with a concomitant reduction of those in the
G2/M and S phases. Additionally, compound 5m significantly and dose-dependently reduced the
amount of phosphorylated retinoblastoma protein detected. Compound 5m enhanced expression
of B cell translocation gene 1, cell cycle-associated proteins (cyclin B1, cyclin D1, and phosphorylated cyclin-dependent kinase 1), and a pro-apoptotic protein (Bcl-2-associated X protein
gene), and activated caspase-3. ADME predictions exposed the oral liability of compounds 5a-s.
we revealed the antiproliferative activity and ADME predictions of the
newly-synthesized compounds 5a–s and provided a detailed insight into the pharmacological
profile of compound 5m. Thus, compounds 5a–s can potentially be exploited as new
antiproliferative lead compounds for cancer chemotherapeutic.

• Publication Work Type: بحث
• Publisher Name: Dove press
• Volume Number: 14
• Magazine \ Newspaper: Drug Design, Development and Therapy
• Pages: 483–495