POLYCYCLIC QUINOLONES (PART 1) - THIENO[2,3-b]BENZO[h]QUINOLINE DERIVATIVES: DESIGN, SYNTHESIS, PRELIMINARY IN VITRO AND IN SILICO STUDIES

Heterocyclic systems with a quinoline nucleus represent the most spectacular example of privileged molecules in medicinal chemistry, as their biological activities are surely affected by changes in structural features. Quin line derivatives have been shown to display a wide spectrum of biological activities such as antibacterial, antifungal, antiparasitic, antiviral, cytotoxic and anti-inflammatory activities. In this study, several 7-hydroxy-8-oxo-8,9-dihydrobenzo[h]thieno[2,3-b]quinoline-9-carboxylic acids were designed, synthesized, and were further subjected to chemical reactions such as alkylation and annelation. The synthesized compounds were also subjected to docking study and biological evaluation. This work was mainly designed to shed light on the requirements for the quinoline nucleus to act as an anticancer agent. Unexpectedly, the synthesized derivatives showed weak or no cytotoxicity against cancer cell lines and the increase in the extent of aromatic/condensed rings did not increase the affinity toward the double stranded DNA. Our virtual screening demonstrated that the chelation with Mg2+ is a determining factor in the expected interaction with Topoisomerases. Key synthetic issues, crystallographic and docking studies have also been described.