Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics

Doudou Zhang,Qingguo Meng,Yi Bi,Ruodong Wang,Yucheng Cao,Kaiyi Wang,Zhuoyue Shi

doi:10.3390/molecules26195969

Doudou Zhang, Qingguo Meng + Show 5 more

Open Access

https://doi.org/10.3390/molecules26195969

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Journal: Molecules	Publication Date: Oct 1, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Yantai University

Abstract

The improper use of antibiotics has led to the development of bacterial resistance, resulting in fewer antibiotics for many bacterial infections. Especially, the drug resistance of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is distinctly serious. This research designed and synthesized two series of 3-substituted ocotillol derivatives in order to improve their anti-HA-MRSA potency and synergistic antibacterial activity. Among the synthesized compounds, 20–31 showed minimum inhibitory concentration (MIC) values of 1–64 µg/mL in vitro against HA-MRSA 18–19, 18–20, and S. aureus ATCC29213. Compound 21 showed the best antibacterial activity, with an MIC of 1 μg/mL and had synergistic inhibitory effects. The fractional inhibitory concentration index (FICI) value was 0.375, when combined with chloramphenicol (CHL) or kanamycin (KAN). The structure–activity relationships (SARs) of ocotillol-type derivatives were also summarized. Compound 21 has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA.

Highlights

IntroductionMost bacteria (e.g., Mycobacterium tuberculosis, Escherichia coli, and Staphylococcus aureus) can cause severe human diseases (e.g., tuberculosis, sepsis, and skin infections) [1,2]
Our preliminary research found found that ocotillol-type ginsenosides have good antibacterial activity, such preliminary research that ocotillol-type ginsenosides have good antibacterial activity, nary research found that ocotillol-type ginsenosides have good antibacterial activity, such as (20S, 24S)-ocotillol with with an minimum inhibitory concentration (MIC)
Our previous research showed that ocotillol-type derivatives have good antibacterial activity against community-acquired methicillin-resistant Staphylococcus aureus (MRSA) (CA-MRSA)

Summary

Introduction

Most bacteria (e.g., Mycobacterium tuberculosis, Escherichia coli, and Staphylococcus aureus) can cause severe human diseases (e.g., tuberculosis, sepsis, and skin infections) [1,2]. Because of the improper use and abuse of antibiotics, many bacteria have become resistant or even cross-resistant to many antibacterial drugs on the market, such as methicillin, chloramphenicol (CHL), and kanamycin (KAN) [3,4]. Diseases and deaths caused by drug-resistant bacterial infections have resulted in great losses to human health and property [5]. The World Health Organization prioritized 20 drug-resistant bacteria on the basis of indicators, such as mortality, resistance rates, health care burden, 10-year resistance trends, and transmissibility, which showed that methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) ranked the highest [6]

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