Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids
With the overuse and misuse of antimicrobial drugs, antibacterial resistance is becoming a critical global health problem. New antibacterial agents are effective measures for overcoming the crisis of drug resistance. In this paper, a novel set of ciprofloxacin-indole/acetophenone hybrids was designe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6325 |
| _version_ | 1797582136372363264 |
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| author | Mingxia Song Yi Hua Yuxin Liu Xunli Xiao Haihong Yu Xianqing Deng |
| author_facet | Mingxia Song Yi Hua Yuxin Liu Xunli Xiao Haihong Yu Xianqing Deng |
| author_sort | Mingxia Song |
| collection | DOAJ |
| description | With the overuse and misuse of antimicrobial drugs, antibacterial resistance is becoming a critical global health problem. New antibacterial agents are effective measures for overcoming the crisis of drug resistance. In this paper, a novel set of ciprofloxacin-indole/acetophenone hybrids was designed, synthesized, and structurally elucidated with the help of NMR and high-resolution mass spectrometry. The in vitro antibacterial activities of these hybrids against gram-positive and gram-negative pathogens, including four multidrug-resistant clinical isolates, were evaluated and compared with those of the parent drug ciprofloxacin (CIP). All the target compounds (MIC = 0.0625–32 μg/mL) exhibited excellent inhibitory activity against the strains tested. Among them, <b>3a</b> (MIC = 0.25–8 μg/mL) showed comparable or slightly less potent activity than CIP. The most active hybrid, <b>8b</b> (MIC = 0.0626–1 μg/mL), showed equal or higher activity than CIP. Moreover, compound <b>8b</b> showed superior bactericidal capability to CIP, with undetectably low resistance frequencies. Furthermore, molecular docking studies conducted showed that <b>8b</b> and CIP had a similar binding mode to DNA gyrase (<i>Staphylocouccus aureus</i>). Thus, hybrids <b>3a</b> and <b>8b</b> could act as a platform for further investigations. |
| first_indexed | 2024-03-10T23:16:37Z |
| format | Article |
| id | doaj.art-a3b77dac8f5348c0a1cf5ef7ef0b52ef |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:16:37Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a3b77dac8f5348c0a1cf5ef7ef0b52ef2023-11-19T08:34:25ZengMDPI AGMolecules1420-30492023-08-012817632510.3390/molecules28176325Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole HybridsMingxia Song0Yi Hua1Yuxin Liu2Xunli Xiao3Haihong Yu4Xianqing Deng5Affiliated Hospital of Jinggangshan University, Ji’an 343000, ChinaHealth Science Center, Jinggangshan University, Ji’an 343009, ChinaAffiliated Hospital of Jinggangshan University, Ji’an 343000, ChinaAffiliated Hospital of Jinggangshan University, Ji’an 343000, ChinaHealth Science Center, Jinggangshan University, Ji’an 343009, ChinaAffiliated Hospital of Jinggangshan University, Ji’an 343000, ChinaWith the overuse and misuse of antimicrobial drugs, antibacterial resistance is becoming a critical global health problem. New antibacterial agents are effective measures for overcoming the crisis of drug resistance. In this paper, a novel set of ciprofloxacin-indole/acetophenone hybrids was designed, synthesized, and structurally elucidated with the help of NMR and high-resolution mass spectrometry. The in vitro antibacterial activities of these hybrids against gram-positive and gram-negative pathogens, including four multidrug-resistant clinical isolates, were evaluated and compared with those of the parent drug ciprofloxacin (CIP). All the target compounds (MIC = 0.0625–32 μg/mL) exhibited excellent inhibitory activity against the strains tested. Among them, <b>3a</b> (MIC = 0.25–8 μg/mL) showed comparable or slightly less potent activity than CIP. The most active hybrid, <b>8b</b> (MIC = 0.0626–1 μg/mL), showed equal or higher activity than CIP. Moreover, compound <b>8b</b> showed superior bactericidal capability to CIP, with undetectably low resistance frequencies. Furthermore, molecular docking studies conducted showed that <b>8b</b> and CIP had a similar binding mode to DNA gyrase (<i>Staphylocouccus aureus</i>). Thus, hybrids <b>3a</b> and <b>8b</b> could act as a platform for further investigations.https://www.mdpi.com/1420-3049/28/17/6325antibacterialAMRciprofloxacinindolehybrid |
| spellingShingle | Mingxia Song Yi Hua Yuxin Liu Xunli Xiao Haihong Yu Xianqing Deng Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids Molecules antibacterial AMR ciprofloxacin indole hybrid |
| title | Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids |
| title_full | Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids |
| title_fullStr | Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids |
| title_full_unstemmed | Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids |
| title_short | Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids |
| title_sort | design synthesis and antimicrobial activity evaluation of ciprofloxacin indole hybrids |
| topic | antibacterial AMR ciprofloxacin indole hybrid |
| url | https://www.mdpi.com/1420-3049/28/17/6325 |
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