{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:06:48Z","timestamp":1788980808644,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672601"],"award-info":[{"award-number":["31672601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Due to the increasing problem of bacterial resistance worldwide, the demand for new antibiotics is becoming increasingly urgent. We wished to: (a) prepare hybrid molecules by linking different pharmacophores by chemical bonds; (b) investigate the antib acterial activity of these hybrids using drug\u2010sensitive and drug\u2010resistant pathogens in vitro and <jats:italic>vivo<\/jats:italic>. A series of hybrid molecules with a diester structure were designed and synthesized that linked amoxicillin and derivatives of benzoic acid via a methylene bridge. Synthesized compounds were evaluated for activities against Gram\u2010positive bacteria (<jats:italic>Staphylococcus aureus<\/jats:italic> American Type Culture Collection [ATCC] 29213, ATCC 11632; methicillin\u2010resistant <jats:italic>S. aureus<\/jats:italic> [MRSA] 11; <jats:italic>Escherichia coli<\/jats:italic> ATCC 25922) and Gram\u2010negative bacteria (<jats:italic>Salmonella<\/jats:italic> LS677, GD836, GD828, GD3625) by microdilution of broth. Synthesized compounds showed good activity against Gram\u2010positive and Gram\u2010negative bacteria in vitro. In particular, amoxicillin\u2010<jats:italic>p<\/jats:italic>\u2010nitrobenzoic acid (<jats:bold>6d<\/jats:bold>) showed good activity against <jats:italic>Salmonella<\/jats:italic> species and had better activity against methicillin\u2010resistant <jats:italic>S. aureus<\/jats:italic> (minimum inhibitory concentration [MIC] = 64\u2009\u03bcg\/ml) than the reference drug, amoxicillin (MIC = 128\u2009\u03bcg\/ml). Amoxicillin\u2010<jats:italic>p<\/jats:italic>\u2010methoxybenzoic acid (<jats:bold>6b<\/jats:bold>) had the best antibacterial activity in vivo (ED<jats:sub>50<\/jats:sub> = 13.2496\u2009\u03bcg\/ml). The hybrid molecules of amoxicillin and derivatives of benzoic acid synthesized based on a diester structure can improve the activity of amoxicillin against <jats:italic>Salmonella<\/jats:italic> species and even improve the activity against MRSA.<\/jats:p>","DOI":"10.1002\/ddr.21739","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T08:49:44Z","timestamp":1600678184000},"page":"198-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and antimicrobial activity of the hybrid molecules between amoxicillin and derivatives of benzoic acid"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-2503","authenticated-orcid":false,"given":"Zhonglin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangzhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Chemical R&amp;D Department Guangdong Dahuanong Animal Health Products Co. Ltd.  Yunfu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikun","family":"Pan","sequence":"additional","affiliation":[{"name":"Chemical R&amp;D Department Guangdong Dahuanong Animal Health Products Co. Ltd.  Yunfu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine South China Agricultural University  Guangzhou China"},{"name":"Chemical R&amp;D Department Guangdong Dahuanong Animal Health Products Co. Ltd.  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