{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:48:29Z","timestamp":1793162909178,"version":"4.5.0"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","award":["5-123\/2016(IC)"],"award-info":[{"award-number":["5-123\/2016(IC)"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the vast availability of antibiotics, bacterial infections remain a leading cause of death worldwide. In an effort to enhance the armamentarium against resistant bacterial strains, 1,2,3-triazole (5a\u2013x) and sulfonate (7a\u2013j) analogues of natural bioactive precursors were designed and synthesized. Preliminary screening against two Gram-positive (Streptococcus pneumoniae and Enterococcus faecalis) and four Gram-negative bacterial strains (Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Escherichia coli) was performed to assess the potency of these analogues as antibacterial agents. Among all triazole analogues, 5e (derived from carvacrol) and 5u (derived from 2-hydroxy 1,4-naphthoquinone) bearing carboxylic acid functionality emerged as potent antibacterial agents against S. pneumoniae (IC50: 62.53 and 39.33 \u03bcg\/mL), E. faecalis (IC50: 36.66 and 61.09 \u03bcg\/mL), and E. coli (IC50: 15.28 and 22.57 \u03bcg\/mL). Furthermore, 5e and 5u also demonstrated moderate efficacy against multidrug-resistant E. coli strains and were therefore selected for further biological studies. Compound 5e in combination with ciprofloxacin displayed a synergistic effect on multidrug-resistant E. coli MRA11 and MRC17 strains, whereas compound 5u was selective against E. coli MRA11 strain. Growth kinetic studies on S. pneumoniae and E. coli treated with 5e and 5u showed an extended lag phase. 5e and 5u did not show significant cytotoxicity up to 100 \u03bcg\/mL concentration on human embryonic kidney (HEK293) cells. Transmission electron microscopic (TEM) analysis of bacterial cells (S. pneumoniae and E. coli) exposed to 5e and 5u clearly showed morphological changes and damaged cell walls. Moreover, these compounds also significantly inhibited biofilm formation in S. pneumoniae and E. coli strains, which was visualized by scanning electron microscopic (SEM) analysis. Treatment of larvae of Galleria mellonella (an in vivo model for antimicrobial studies) with 5e and 5u did not cause an alteration in the hemocyte density, thereby indicating lack of an immune response, and were nontoxic up to a concentration of 2.5 mg\/mL.<\/jats:p>","DOI":"10.1021\/acsomega.8b00582","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T08:39:23Z","timestamp":1530002363000},"page":"6912-6930","source":"Crossref","is-referenced-by-count":73,"title":["Natural Product-Based 1,2,3-Triazole\/Sulfonate Analogues as Potential Chemotherapeutic\nAgents for Bacterial Infections"],"prefix":"10.1021","volume":"3","author":[{"given":"Babita","family":"Aneja","sequence":"first","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]},{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudsser","family":"Azam","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadab","family":"Alam","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Perwez","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Maguire","sequence":"additional","affiliation":[{"name":"Maynooth University , , ,","place":["Co. Kildare, Ireland, ABC127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9127-532X","authenticated-orcid":true,"given":"Umesh","family":"Yadava","sequence":"additional","affiliation":[{"name":"Deen Dayal Upadhyay Gorakhpur University , , , ,","place":["Gorakhpur, Uttar Pradesh, India, 273009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Maynooth University , , ,","place":["Co. Kildare, Ireland, ABC127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin G.","family":"Daniliuc","sequence":"additional","affiliation":[{"name":"Westfa\u0308lische Wilhelm-Universita\u0308t , , ,","place":["Mu\u0308nster, Germany, 48149"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Moshahid A.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qazi Mohd. Rizwanul","family":"Haq","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-8451","authenticated-orcid":true,"given":"Mohammad","family":"Abid","sequence":"additional","affiliation":[{"name":"Jamia Millia Islamia , , , Jamia Nagar, ,","place":["New Delhi, India, 110025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"2026090210505333200_cit1","doi-asserted-by":"publisher","first-page":"9767","DOI":"10.1021\/acs.inorgchem.6b01574","article-title":"Antimicrobial Properties of Tris(homoleptic)\nRuthenium(II) 2-Pyridyl-1,2,3-triazole \u201cClick\u201d Complexes\nagainst Pathogenic Bacteria, Including Methicillin-Resistant Staphylococcus\naureus (MRSA)","volume":"55","author":"Kumar","year":"2016","journal-title":"Inorg. Chem."},{"key":"2026090210505333200_cit2","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1021\/ml100057z","article-title":"Synthesis and biological\nevaluation of muraymycin analogues\nactive against anti-drug-resistant bacteria","volume":"1","author":"Tanino","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"2026090210505333200_cit3","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1021\/nn507168x","article-title":"Killing mechanism\nof stable N-halamine cross-linked polymethacrylamide\nnanoparticles that selectively target bacteria","volume":"9","author":"Natan","year":"2015","journal-title":"ACS Nano"},{"key":"2026090210505333200_cit4","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.1021\/ja408505n","article-title":"Nanoscale\nStructure-Activity Relationships, Mode of Action, and Biocompatibility\nof Gold Nanoparticle Antibiotics","volume":"136","author":"Bresee","year":"2014","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026090210505333200_cit5","unstructured":"Frieden, T.\n          \n          Antibiotic resistance\nthreats in the United States. http:\/\/www.cdc.gov\/drugresistance\/threat-report-2013\/index.html, 2013."},{"key":"2026090210505333200_cit6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093414","article-title":"The\nnatural antimicrobial carvacrol inhibits quorum sensing in Chromobacterium violaceum and reduces bacterial biofilm\nformation at sub-lethal concentrations","volume":"9","author":"Burt","year":"2014","journal-title":"PLoS\nOne"},{"key":"2026090210505333200_cit7","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.1016\/j.bmcl.2010.04.042","article-title":"Identification\nof aryl 2-aminoimidazoles\nas biofilm inhibitors in Gram-negative bacteria","volume":"20","author":"Bunders","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090210505333200_cit8","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1021\/acsinfecdis.5b00055","article-title":"Cell-based high-throughput\nscreening identifies rifapentine as an inhibitor of amyloid and biofilm\nformation in Escherichia coli","volume":"1","author":"Maher","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"2026090210505333200_cit9","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1021\/bm500422v","article-title":"Nanoparticle (star\npolymer) delivery of nitric oxide effectively\nnegates Pseudomonas aeruginosa biofilm\nformation","volume":"15","author":"Duong","year":"2014","journal-title":"Biomacromolecules"},{"key":"2026090210505333200_cit10","doi-asserted-by":"publisher","first-page":"5476","DOI":"10.1039\/c1ob05605k","article-title":"Flustramine inspired synthesis and\nbiological evaluation of pyrroloindoline triazole amides as novel\ninhibitors of bacterial biofilms","volume":"9","author":"Bunders","year":"2011","journal-title":"Org. 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Lett."},{"key":"2026090210505333200_cit17","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/j.tetlet.2009.01.125","article-title":"Synthesis\nof a polyprenyl-type library containing 1,4-disubstituted-1,2,3-triazoles\nwith anti-biofilm activities against Pseudoalteromonas sp","volume":"50","author":"Praud-Tabaries","year":"2009","journal-title":"Tetrahedron Lett."},{"key":"2026090210505333200_cit18","doi-asserted-by":"publisher","first-page":"834","DOI":"10.3109\/14756366.2015.1058257","article-title":"Monocyclic \u03b2-lactam and unexpected oxazinone formation: Synthesis,\ncrystal structure, docking studies and antibacterial evaluation","volume":"31","author":"Aneja","year":"2016","journal-title":"J. Enzyme Inhib. Med. 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Med.\nChem."},{"key":"2026090210505333200_cit24","unstructured":"Small-Molecule\nDrug Discovery Suite 2017-3; Schro\u0308dinger,\nLLC: New York,\nNY, 2017."},{"key":"2026090210505333200_cit25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/s0169-409x(00)00129-0","article-title":"Experimental and\ncomputational approaches to estimate solubility and permeability in\ndrug discovery and development settings1PII of original article: S0169-409X(96)00423-1.\nThe article was originally published in Advanced Drug Delivery Reviews\n23 (1997) 3-25.1","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. 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A: Chem."},{"key":"2026090210505333200_cit28","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1107\/s0108767303005488","article-title":"Multiparametric scaling\nof diffraction intensities","volume":"59","author":"Otwinowski","year":"2003","journal-title":"Acta Crystallogr.,\nSect. A: Found. Crystallogr."},{"key":"2026090210505333200_cit29","unstructured":"SADABS; Bruker AXS Inc.: Madison, WI, USA, 2014."},{"key":"2026090210505333200_cit30","unstructured":"Hooft, R. W. 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Microbiol."},{"key":"2026090210505333200_cit42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175710","article-title":"Effect of\nquinoline\nbased 1,2,3-triazole and its structural analogues on growth and virulence\nattributes of Candida albicans","volume":"12","author":"Irfan","year":"2017","journal-title":"PLoS One"},{"key":"2026090210505333200_cit43","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1128\/iai.58.11.3465-3468.1990","article-title":"Regulation\nof the magnitude of the antibody response to bacterial polysaccharide\nantigens by thymus-derived lymphocytes","volume":"58","author":"Baker","year":"1990","journal-title":"Infect.\nImmun."},{"key":"2026090210505333200_cit44","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.74.1.17","article-title":"Studies on the mechanism\nof immunological paralysis induced in mice by pneumococcal polysaccharides","volume":"74","author":"Felton","year":"1955","journal-title":"J. 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Microbiol."},{"key":"2026090210505333200_cit46","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.1016\/j.biomaterials.2008.08.016","article-title":"The inhibition\nof Staphylococcus epidermidis biofilm formation by\nvancomycin-modified titanium alloy and implications for the treatment\nof periprosthetic infection","volume":"29","author":"Antoci","year":"2008","journal-title":"Biomaterials"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.8b00582","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/3\/6\/6912\/67804836\/acsomega.8b00582.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/3\/6\/6912\/67804836\/acsomega.8b00582.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:50:58Z","timestamp":1788360658000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/3\/6\/6912\/744743\/Natural-Product-Based-1-2-3-Triazole-Sulfonate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,26]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6,26]]},"published-print":{"date-parts":[[2018,6,30]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.8b00582","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,26]]}}}