# Isolation of Dual-Active Drugs with Anticancer and Antibacterial Activities That Target Both Tubulin and FtsZ

## TL;DR

This study identifies drugs that can fight both cancer and bacterial infections by targeting similar proteins in cancer cells and bacteria.

## Contribution

The discovery of dual-active drugs targeting both tubulin and FtsZ offers a novel approach to treating cancer and bacterial infections simultaneously.

## Key findings

- Six compounds showed both anticancer and antibacterial activities in vitro.
- Compound 23 was the most effective, with strong anticancer activity and antibacterial effects against multiple bacteria.
- Compound 23 inhibited FtsZ and caused elongated cell morphology in Bacillus subtilis.

## Abstract

Background: Cancer patients experience a high incidence of concomitant infections due to the effects of chemotherapy drugs and their suppressed immune function. Infection has become a major cause and an accelerating factor of cancer-related deaths. The combined use of anticancer drugs and antibiotics can produce adverse effects, necessitating the urgent search for dual-active drugs that are effective against both cancer and bacteria. Since tubulin has a homologous protein filamenting temperature-sensitive mutant Z (FtsZ) in bacteria, tubulin inhibitors have the potential to emerge as dual-active drugs against both cancer and bacteria. Methods: A comprehensive screening of a tubulin inhibitor library, encompassing 196 compounds, was conducted to evaluate their various activities. Results: Compounds 6, 23, 33, 56, 60, and 71 exhibited both anticancer and antibacterial activities in vitro, and 23, 33, 56, and 60 displayed varying degrees of FtsZ inhibitory activity. Particularly, compound 23 stood out as the most potent, exhibiting not only the strongest anticancer activity with IC50 values of 12, 20, and 10 nM against A549, MCF-7 and Hela cells, respectively, but also the most exceptional antibacterial activity with minimum inhibitory concentration (MIC) values of 8, 8, 64, and 32 μM against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), respectively. Furthermore, compound 23 possessed the superior FtsZ inhibitory activity, facilitating polymerization. This was evident in the remarkably elongated cell morphology of Bacillus subtilis treated with compound 23. To gain a deeper understanding of the underlying mechanisms, molecular docking studies were conducted, revealing the interaction mode between compound 23 and both tubulin and FtsZ, further elucidating its multifaceted biological activities. Conclusions: The dual-active drugs obtained in this study provide a new solution to the problem of bacterial infection in cancer patients. The revealed FtsZ as the antibacterial target provides an important theoretical basis for further optimization of such drugs.