Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics
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 <i>Staphylococcus aureus</i> (HA-MRSA) is distinctly serious. This...
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/19/5969 |
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| author | Doudou Zhang Yucheng Cao Kaiyi Wang Zhuoyue Shi Ruodong Wang Qingguo Meng Yi Bi |
| author_facet | Doudou Zhang Yucheng Cao Kaiyi Wang Zhuoyue Shi Ruodong Wang Qingguo Meng Yi Bi |
| author_sort | Doudou Zhang |
| collection | DOAJ |
| description | 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 <i>Staphylococcus aureus</i> (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, <b>20</b>–<b>31</b> showed minimum inhibitory concentration (MIC) values of 1–64 µg/mL in vitro against HA-MRSA 18–19, 18–20, and <i>S. aureus</i> ATCC29213. Compound <b>21</b> 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 <b>21</b> has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA. |
| first_indexed | 2024-03-10T06:54:02Z |
| format | Article |
| id | doaj.art-661eebe3be2748acba5d4a158700ceec |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:54:02Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-661eebe3be2748acba5d4a158700ceec2023-11-22T16:35:21ZengMDPI AGMolecules1420-30492021-10-012619596910.3390/molecules26195969Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional AntibioticsDoudou Zhang0Yucheng Cao1Kaiyi Wang2Zhuoyue Shi3Ruodong Wang4Qingguo Meng5Yi Bi6School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, ChinaThe 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 <i>Staphylococcus aureus</i> (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, <b>20</b>–<b>31</b> showed minimum inhibitory concentration (MIC) values of 1–64 µg/mL in vitro against HA-MRSA 18–19, 18–20, and <i>S. aureus</i> ATCC29213. Compound <b>21</b> 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 <b>21</b> has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA.https://www.mdpi.com/1420-3049/26/19/5969ocotillol-type derivativesHA-MRSAantibioticsstructural modificationsynergistic effects |
| spellingShingle | Doudou Zhang Yucheng Cao Kaiyi Wang Zhuoyue Shi Ruodong Wang Qingguo Meng Yi Bi Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics Molecules ocotillol-type derivatives HA-MRSA antibiotics structural modification synergistic effects |
| title | Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics |
| title_full | Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics |
| title_fullStr | Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics |
| title_full_unstemmed | Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics |
| title_short | Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics |
| title_sort | design synthesis and antibacterial evaluation of novel ocotillol derivatives and their synergistic effects with conventional antibiotics |
| topic | ocotillol-type derivatives HA-MRSA antibiotics structural modification synergistic effects |
| url | https://www.mdpi.com/1420-3049/26/19/5969 |
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