{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:19:52Z","timestamp":1788344392189,"version":"build-2803163510"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T00:00:00Z","timestamp":1570406400000},"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":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-aminopenicillanic acid using benzyl alcohol and thionyl chloride succeeded by azide displacement using trifluoromethanesulfonyl azide in dichloromethane. The azide thus formed was reacted with substituted alkynes to furnish benzyl-protected penicillin\u2013triazole conjugates. Benzyl deprotection of the conjugates resulted in furnishing PNTCs under water methanol mixture using Pd\/C as a catalyst. The PNTCs (7a\u2013j) formed were screened for in vitro antibacterial potency against pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes and antifungal potency against Candida albicans, Aspergillus niger, and Aspergillus clavatus. Further antimicrobial evaluation revealed compounds 7c, 7d, 7e, 7g, and 7i to be the most compounds of the series with minimum inhibitory concentration value for antibacterial in the range 0.5\u201350 \u03bcg\/mL and for antifungal in the range 9\u2013300 \u03bcg\/mL. Toxicological analysis documented for compounds 7c, 7d, 7e, 7g, and 7i revealed compound 7i to be the most promising member of the series with 1000 and 500 mg\/kg LD50, and no-observed-adverse-effect level to facilitate future clinical studies of the same.<\/jats:p>","DOI":"10.1021\/acsomega.9b01724","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T09:05:10Z","timestamp":1570439110000},"page":"17230-17235","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis, Pharmacological and Toxicological Screening\nof Penicillin\u2013Triazole Conjugates (PNTCs)"],"prefix":"10.1021","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5190-8236","authenticated-orcid":true,"given":"Adarsh","family":"Sahu","sequence":"first","affiliation":[{"name":"Dr. Harisingh Gour Vishwavidyalaya , , , ,","place":["Sagar, Madhya Pradesh, India, 470003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Sahu","sequence":"additional","affiliation":[{"name":"Central University of Kerala , , , ,","place":["Periye, Kerala, India, 671320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkishore","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Dr. Harisingh Gour Vishwavidyalaya , , , ,","place":["Sagar, Madhya Pradesh, India, 470003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,10,7]]},"reference":[{"key":"2026090206020179200_cit1","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature17042","article-title":"Antibacterial drug\ndiscovery in the resistance era","volume":"529","author":"Brown","year":"2016","journal-title":"Nature"},{"key":"2026090206020179200_cit2","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1021\/cr030102i","article-title":"Bacterial\nresistance to \u03b2-lactam\nantibiotics: compelling opportunism, compelling opportunity","volume":"105","author":"Fisher","year":"2005","journal-title":"Chem. Rev."},{"key":"2026090206020179200_cit3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3389\/fmicb.2010.00134","article-title":"A brief\nhistory of the antibiotic era: lessons learned and challenges for\nthe future","volume":"1","author":"Aminov","year":"2010","journal-title":"Front. Microbiol."},{"key":"2026090206020179200_cit4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/14740338.2018.1462334","article-title":"An update on adverse\ndrug reactions related to \u03b2-lactam antibiotics","volume":"17","author":"Vardakas","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"2026090206020179200_cit5","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms\nfor antibiotic discovery","volume":"12","author":"Lewis","year":"2013","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026090206020179200_cit6","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1128\/AAC.26.3.410","article-title":"Comparison\nof the activities of penicillin G and new beta-lactam antibiotics\nagainst clinical isolates of Bacteroides species","volume":"26","author":"Aldridge","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090206020179200_cit7","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1021\/js970315l","article-title":"Current perspectives\non pain upon injection of drugs","volume":"87","author":"Brazeau","year":"1998","journal-title":"J. Pharm. Sci."},{"key":"2026090206020179200_cit8","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/j.ejmech.2005.02.013","article-title":"Synthesis, characterization and antimicrobial activity\nof some substituted 1, 2, 3-triazoles","volume":"40","author":"Holla","year":"2005","journal-title":"Eur.\nJ. Med. Chem."},{"key":"2026090206020179200_cit9","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.bmcl.2008.12.026","article-title":"Synthesis\nand antifungal activity\nof 1, 2, 3-triazole containing fluconazole analogues","volume":"19","author":"Aher","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090206020179200_cit10","first-page":"107","article-title":"Increasing\nincidence of bacterial resistance to antibiotics by isolates from\nthe urinary tract","volume":"8","author":"Ozumba","year":"2005","journal-title":"Niger. J. Clin. Pract."},{"key":"2026090206020179200_cit11","first-page":"1684","article-title":"Degradation\nof \u03b2-lactam antibiotics","volume":"87","author":"Deshpande","year":"2004","journal-title":"Curr. Sci."},{"key":"2026090206020179200_cit12","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.bmcl.2018.11.038","article-title":"Synthesis and evaluation\nof biological activity for dual-acting antibiotics on the basis of\nazithromycin and glycopeptides","volume":"29","author":"Tevyashova","year":"2019","journal-title":"Bioorg. Med.\nChem. Lett."},{"key":"2026090206020179200_cit13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.ejmech.2018.05.055","article-title":"\u201cSynthesis,\ncrystal structure\nand antimicrobial potential of some fluorinated chalcone-1,2,3-triazole\nconjugates.\u201d","volume":"155","author":"Yadav","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"2026090206020179200_cit14","doi-asserted-by":"publisher","first-page":"9219","DOI":"10.1002\/chem.201500982","article-title":"3, 6, 7-Triamino-[1,\n2, 4] triazolo [4, 3-b][1, 2, 4] triazole: A Non-toxic, High-Performance\nEnergetic Building Block with Excellent Stability","volume":"21","author":"Klapo\u0308tke","year":"2015","journal-title":"Chem. - Eur. J."},{"key":"2026090206020179200_cit15","doi-asserted-by":"publisher","first-page":"3527","DOI":"10.1016\/j.bmc.2016.05.060","article-title":"Synthesis,\nantimalarial properties and 2D-QSAR studies of novel triazole-quinine\nconjugates","volume":"24","author":"Faidallah","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090206020179200_cit16","doi-asserted-by":"publisher","first-page":"6029","DOI":"10.1016\/0040-4039(96)01307-X","article-title":"Metal catalyzed\ndiazo transfer for\nthe synthesis of azides from amines","volume":"37","author":"Alper","year":"1996","journal-title":"Tetrahedron\nLett."},{"key":"2026090206020179200_cit17","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1021\/ol034919+","article-title":"Simple conversion of\naromatic amines into azides","volume":"5","author":"Liu","year":"2003","journal-title":"Org. Lett."},{"key":"2026090206020179200_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102939","article-title":"Synthesis and systemic toxicity assessment\nof quinine-triazole scaffold with antiprotozoal potency","author":"Sahu","year":"2019","journal-title":"Bioorg. Chem."},{"key":"2026090206020179200_cit19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1039\/B9PY00217K","article-title":"Exponential\ngrowth of functional\npoly (glutamic acid) dendrimers with variable stereochemistry","volume":"1","author":"Hartwig","year":"2010","journal-title":"Polym. Chem."},{"key":"2026090206020179200_cit20","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.arabjc.2015.08.008","article-title":"Green synthesized silver\nnanoparticles destroy multidrug resistant\nbacteria via reactive oxygen species mediated membrane damage","volume":"10","author":"Das","year":"2017","journal-title":"Arab. J. Chem."},{"key":"2026090206020179200_cit21","doi-asserted-by":"publisher","first-page":"94457","DOI":"10.1371\/journal.pone.0094457","article-title":"In vitro selection\nand characterization of new probiotic candidates from table olive\nmicrobiota","volume":"9","author":"Botta","year":"2014","journal-title":"PLoS One"},{"key":"2026090206020179200_cit22","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.1021\/jm0102396","article-title":"(). Antimalarial simplified 3-aryltrioxanes: Synthesis\nand preclinical efficacy\/toxicity testing in rodents","volume":"44","author":"Posner","year":"2001","journal-title":"J. Med. Chem."},{"key":"2026090206020179200_cit23","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.jhazmat.2011.01.054","article-title":"Health\nrisk characterisation for environmental pollutants\nwith a new concept of overall risk probability","volume":"187","author":"Cao","year":"2011","journal-title":"J. Hazard. Mater."},{"key":"2026090206020179200_cit24","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.lfs.2019.05.004","article-title":"Bio-isosteric replacement of amide\ngroup with 1,2,3-triazole in phenacetin improves the toxicology and\nefficacy of phenacetin-triazole conjugates (PhTCs)","volume":"228","author":"Sahu","year":"2019","journal-title":"Life Sci."},{"key":"2026090206020179200_cit25","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.yrtph.2017.10.025","article-title":"Safety evaluation\nof auraptene in rats in acute and\nsubacute toxicity studies","volume":"91","author":"Vakili","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"2026090206020179200_cit26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide\nfor dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.9b01724","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/4\/17\/17230\/67682750\/acsomega.9b01724.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/4\/17\/17230\/67682750\/acsomega.9b01724.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:02:11Z","timestamp":1788343331000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/4\/17\/17230\/615798\/Synthesis-Pharmacological-and-Toxicological"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,7]]},"references-count":26,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2019,10,7]]},"published-print":{"date-parts":[[2019,10,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.9b01724","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,7]]}}}