High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes

Md Salman Shakil,Shahida Parveen,Christian G Hartinger,Mayur Azam,Fearghal Walsh,Rhonda J Rosengren,Tilo Söhnel,Muhammad Ashraf Shaheen,Sanam Movassaghi,Stephen M F Jamieson,Muhammad Hanif,Zohaib Rana

doi:10.3390/biomedicines9020123

Abstract

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a–1c and 3-hydroxy-4-thiopyridones 1d–1f as well as their Ru(η6-p-cymene)Cl complexes 2a–2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d–1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low μM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.

Highlights

Hydroxypyrones are a class of naturally occurring, biocompatible, heterocyclic ketones, with a hydroxyl group in the ortho or para position
The results presented are from three independent experiments performed in triplicate
The results showed that the single-cell colony-formation ab of both cell lines decreased significantly compared to the control (Figure 5)

Summary

Introduction

Hydroxypyrones are a class of naturally occurring, biocompatible, heterocyclic ketones, with a hydroxyl group in the ortho or para position. Some examples, such as maltol, kojic acid, and their analogues (Figure 1), are commercially available and are used in the food and cosmetics industries [1,2,3,4]. The lead derivatives based on deferiprone inhibited HP1-mediated gene

Methods

Discussion

Conclusion