Tachyplesin I and its derivatives: A pharmaco-chemical perspective on their antimicrobial and antitumor potential

ABSTRACT

Introduction

Increasing evidence suggests that intratumor microbiota are an intrinsic component in the tumor microenvironment across multiple cancer types, and that there is a close relationship between microbiota and tumor progression. Therefore, how to address the interaction between bacteria and malignances has become a growing concern. Tachyplesin I (TPI), a peptide with dual antimicrobial and antitumor effects, holds great promise as a therapeutic alternative for the aforementioned diseases, with the advantage of broad-spectrum activities, quick killing efficacy, and a low tendency to induce resistance.

Areas covered

This review comprehensively summarizes the pharmacological mechanisms of TPI with an emphasis on its antimicrobial and antitumor potential. Furthermore, it presents advances in TPI derivatives and gives a perspective on their future development. The article is based on literature searches using PubMed and SciFinder to retrieve the most up-to-date information of TPI.

Expert opinion

Bacterial infections and cancer both pose a serious threat to health due to their symbiotic interactions and drug resistance. TPI is anticipated to be a novel agent to control pathogenic bacteria and various tumors through multiple mechanisms of action. Indeed, the continuous advancements in chemical modification and innovative applications of TPI give hope for future improvements in therapeutic efficacy.

KEYWORDS:

• Tachyplesin I
• antimicrobial and antitumor activity
• Structure–activity relationship
• mechanism of action
• membrane disruption

Article highlights

• TPI is a conformationally constrained β-hairpin peptide with dual antitumor and antibacterial activities

• The bifunctional effects of TPI and its derivatives have the potential to address the interplay between bacteria and malignancies.

• The advantages of TPI on cancer treatment include its broad-spectrum activities, quick killing effects, and low tendency to induce resistance.

• Continuous novel strategies are being applied to aid its targeting ability and efficacy of TPI.

• TPI is a promising therapeutic agent for the simultaneous treatment of bacterial infections and cancer.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was financially supported by the Natural Science Foundation of China (No. 81903654, 82173846 and 82104194), the Chinese Postdoctoral Science Foundation (No. 2021M702215), 2021, the Innovation Action Plan (No. 21S11902800), the Shanghai Rising-Star Program (No. 22QA1409100), the Shanghai Sailing Program (No. 22YF1445000), the Young Talent Lifting Project of the Chinese Association of Chinese Medicine [No. CACM-(2021-QNRC2-A08)], the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202004), and the Three-year Action Plan for Shanghai TCM Development and Inheritance Program [ZY(2021-2023)-0401 and ZY(2021-2023)-0208].