The Privileged Scaffold Quinoline in Derivatives With Anticancer Potential Mediated by Late Apoptosis

Cancer has been described as the perennial second leading cause of death, despite advances in detection and treatment. Considering this disease remains a major public health crisis across the world, scientists have been looking for additional anticancer drugs options. In this context, the privileged scaffold quinoline appears to be an interesting chemical structure to develop new anticancer drugs, especially when more efficient synthetic routes to form these compounds are proposed.

A total of five quinoline derivatives were obtained by applying the adapted methodology of Skraup and Doebner-von Miller and Heck-Mizoroki. The anticancer profile was investigated on cervical cancer (HeLa and Me-180) and chronic myeloid leukemia (K562) cell lines, by using the MTT or FACSVerse flow cytometer assays. Treatment of Vero cells was performed to assess the Selectivity Index, followed by the type of cell death assessment (apoptosis and necrosis) for the most active and safe derivative. ADMET profile was investigated by using SwissADME platform and DataWarrior^® software.

The most promising result was achieved with derivative 3, with best antiproliferative activity especially against cervical cancer cell lines (HeLa: IC₅₀ 15.13 μM and Me-180: IC₅₀ 46.90 μM) and safe profile compared to Vero cells and in silico prediction. The type of cell death was mostly related to late apoptosis. All quinoline derivatives demonstrated druglikeness in agreement with Lipinski and Veber rules.

Our findings provide quinoline derivatives with anticancer activity, which may pave the way for new alternatives for anticancer drug development.