{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:35:28Z","timestamp":1783618528007,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021YFD1800900"],"award-info":[{"award-number":["2021YFD1800900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["25-LZIHPS-02"],"award-info":[{"award-number":["25-LZIHPS-02"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Innovation Engineering of CAAS","award":["2021YFD1800900"],"award-info":[{"award-number":["2021YFD1800900"]}]},{"name":"Science and Technology Innovation Engineering of CAAS","award":["25-LZIHPS-02"],"award-info":[{"award-number":["25-LZIHPS-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The objectives of the study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-indole derivatives. Thirty-seven new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinical resistant Klebsiella pneumoniae (K.\u00a0pneumoniae) isolates. K.\u00a0pneumoniae is an important opportunistic pathogen that often threatens the health of immunocompromised people such as the elderly, children, and ICU patients. The most active compound 4P showed rapid bactericidal activity against resistant K.\u00a0pneumoniae 2108 with MIC and MBC values that were 4 and 8 \u00b5g\/mL, respectively. The hemolytic activity of 4P was low, with an HC50 value of 123.6 \u00b5g\/mL. Compound 4P induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity and was not prone to antibiotic resistance. The dihydrofolate reductase (DHFR) activity was also notably inhibited by 4P in vitro. Molecular docking revealed that the aminoguanidine moiety and indole structure of 4P played an important role in binding to the target site of the K. pneumoniae dihydrofolate reductase (DHFR) receptor. In the mouse pneumonia model caused by K. pneumoniae, 4P improved the survival rate of mice, reduced bacterial loads, and alleviated tissues\u2019 pathological injuries at a dosage of 4 mg\/kg. Therefore, compound 4P may be a promising lead compound or drug candidate for antibacterial purposes against K.\u00a0pneumoniae.<\/jats:p>","DOI":"10.3390\/molecules30040887","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T12:36:57Z","timestamp":1739795817000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis, Antimicrobial Activities, and Model of Action of Indolyl Derivatives Containing Amino-Guanidinium Moieties"],"prefix":"10.3390","volume":"30","author":[{"given":"Yu-Xi","family":"Li","sequence":"first","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8810-0573","authenticated-orcid":false,"given":"Xiang","family":"Geng","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"School of Health Nursing, Fuyang Vocational Technical College, Fuyang 236000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo-Chen","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-7184","authenticated-orcid":false,"given":"Xi-Wang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-0666","authenticated-orcid":false,"given":"Jian-Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ruzante, J.M., Harris, B., Plummer, P., Raineri, R.R., Loy, J.D., Jacob, M., Sahin, O., and Kreuder, A.J. 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