Antibacterial AZT derivative regulates metastasis of breast cancer cells

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Title
Antibacterial AZT derivative regulates metastasis of breast cancer cells
Author(s)
S Chirumarry; Nak Kyun Soung; Junyeol Han; E Y Kim; E K Ryu; Y H Lee; S Y Shin; P Gunasekaran; J K Bang
Bibliographic Citation
European Journal of Medicinal Chemistry, vol. 193, pp. 112233-112233
Publication Year
2020
Abstract
Antimicrobial peptides (AMP) with anticancer activity have drawn remarkable attention in modern treatments. However, long peptide length and protease instability are the most addressing factors, which hampers their further development as therapeutic agents. In view of this, herein, we designed and synthesized a series of AZT-based cationic small molecule incorporating a variety of hydrophobic groups and cationic charges, including amine and guanidine groups to mimic the amphipathic structure of AMPs. These compounds were evaluated for their antibacterial activity against Gram-positive and Gram-negative bacteria. Through an extensive structure activity relationship study (SAR), we identified ADG-2e as the most potent antibacterial agent, which exhibited remarkable potency against drug resistant bacterial strains such as MRSA and MDRPA. Further, ADG-2e was examined for their anti-metastatic ability by investigating the cancer cell migration and invasiveness through scratch wound-healing assay and transwell invasive assay, respectively. In addition, time-lapse cell tracking analysis also performed for analyzing the cell movement pattern. Treatment of ADG-2e against metastatic breast cancer cells (MDA-MB-231) suppressed tumor cell migration by multi-directional lamellipodium formation, indicating their anti-metastatic potential. Thus, our cationic AZT based small molecules may evolve as an appealing class of antibacterial agents with anti-metastasis potential.
Keyword
Amphipathic small moleculeAnti-MetastasisAntibacterialsCell motilityLamellipodia
ISSN
0223-5234
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ejmech.2020.112233
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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