{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:51:11Z","timestamp":1792464671058,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski\u2019s rule of five. <jats:bold>5b<\/jats:bold> showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50\u00a0\u03bcg\/mL concentration. Compounds showed antibacterial activity against various tested strains. <jats:bold>5e and 5f<\/jats:bold> showed a minimum inhibitory concentration (MIC) value of 3.12\u00a0\u03bcg\/mL for <jats:italic>P.aeruginosa<\/jats:italic> and <jats:italic>K<\/jats:italic>.<jats:italic>pneumoniae<\/jats:italic>, respectively. In the antifungal assay, only <jats:bold>5e<\/jats:bold> inhibited one strain with a zone of inhibition &amp;gt;6\u00a0mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; <jats:bold>5c, 5d, and 5f<\/jats:bold> exhibited LC<jats:sub>50 =<\/jats:sub>5.7\u00a0\u03bcg\/mL. In the protein kinase inhibition assay, <jats:bold>5a, 5b,<\/jats:bold> and <jats:bold>5g<\/jats:bold> demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5\u201310.5\u00a0mm for the bald one and 6\u20137.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area.<\/jats:p>","DOI":"10.3389\/fphar.2023.1084181","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T07:16:14Z","timestamp":1677482174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Design, synthesis and screening of indole acetic acid-based tri-azo moieties as antioxidants, anti-microbial and cytotoxic agents"],"prefix":"10.3389","volume":"14","author":[{"given":"Maryam","family":"Javaid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan-Ul","family":"Haq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif-Ullah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Irshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"112652","DOI":"10.1016\/j.ejmech.2020.112652","article-title":"An insight on medicinal attributes of 1,2,4-triazoles","volume":"205","author":"Aggarwal","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"M1189","DOI":"10.3390\/M1189","article-title":"Microwave-assisted synthesis of schiff bases of isoniazid and evaluation of their anti-proliferative and antibacterial activities","volume":"2021","author":"Al-Hiyari","year":"2021","journal-title":"Molbank"},{"key":"B3","doi-asserted-by":"publisher","first-page":"19470","DOI":"10.1039\/D2RA03281C","article-title":"Design and synthesis of hybrid compounds as novel drugs and medicines","volume":"12","author":"Alkhzem","year":"2022","journal-title":"RSC Adv."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10406638.2022.2045329","article-title":"Synthesis, characterization and molecular docking of new nucleosides and schiff bases derived from ampyrone as antiviral agents to contain the COVID-19 virus","volume":"1","author":"Alotaibi","year":"2022","journal-title":"Polycycl. Aromat. Compd."},{"key":"B5","first-page":"5179","article-title":"Syntheses, spectral characterization and biological elucidation of some mannich bases","volume":"24","author":"Amanullah","year":"2012","journal-title":"Asian J. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"474","DOI":"10.3389\/fchem.2019.00474","article-title":"Design, synthesis, and biological evaluation of (E)-N\u2019-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide derivatives as anti-prostate cancer agents","volume":"7","author":"Arjun","year":"2019","journal-title":"Front. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"10908","DOI":"10.3390\/ijms150610908","article-title":"Synthesis and antioxidant activity evaluation of new compounds from hydrazinecarbothioamide and 1,2,4-triazole class containing diarylsulfone and 2,4-difluorophenyl moieties","volume":"15","author":"Barbuceanu","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.ejmech.2008.06.019","article-title":"Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities","volume":"44","author":"Bayrak","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1080\/14756366.2020.1746783","article-title":"Novel sulindac derivatives: Synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity","volume":"35","author":"Bhat","year":"2020","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"252","DOI":"10.5897\/AJPP10.417","article-title":"Antitumor, cytotoxic and antioxidant potential of Aster thomsonii extracts","volume":"5","author":"Bibi","year":"2011","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/0012-1606(75)90238-9","article-title":"DNA-dependent RNA-polymerases from Artemia embryos. Characterization of polymerases I and II from nauplius larvae","volume":"45","author":"Birndorf","year":"1975","journal-title":"Dev. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"450","DOI":"10.3390\/molecules25030450","article-title":"Synthesis of a new series of nitrogen\/sulfur heterocycles by linking four rings: Indole; 1,2,4-triazole; pyridazine; and quinoxaline","volume":"25","author":"Boraei","year":"2020","journal-title":"Molecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1472-6750-2-17","article-title":"A comparison between two brine shrimp assays to detect in vitro cytotoxicity in marine natural products","volume":"2","author":"Carballo","year":"2002","journal-title":"BMC Biotechnol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"100162","DOI":"10.1016\/j.rechem.2021.100162","article-title":"Newly synthesized triazole-based Schiff base ligands and their Co(II) complexes as antimicrobial and anticancer agents: Chemical synthesis, structure and biological investigations","volume":"3","author":"Deodware","year":"2021","journal-title":"Results Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s00044-013-0637-x","article-title":"Antimicrobial and antiquorum-sensing studies. Part 2: Synthesis, antimicrobial, antiquorum-sensing and cytotoxic activities of new series of fused[1,3,4]thiadiazole and [1,3]benzothiazole derivatives","volume":"23","author":"El-Gohary","year":"2014","journal-title":"Med. Chem. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/s12906-015-0891-1","article-title":"Extraction optimization of medicinally important metabolites from Datura innoxia Mill.: An in vitro biological and phytochemical investigation","volume":"15","author":"Fatima","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.85270","article-title":"Antioxidant compounds and their antioxidant mechanism","author":"Francenia Santos-S\u00e1nchez","year":"2019","journal-title":"Antioxidants"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.1007\/s00044-015-1397-6","article-title":"Synthesis and antibacterial activity of Schiff bases and amines derived from alkyl 2-(2-formyl-4-nitrophenoxy)alkanoates","volume":"24","author":"Goszczy\u0144ska","year":"2015","journal-title":"Med. Chem. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.2147\/DDDT.S364746","article-title":"Design, synthesis, and anti-inflammatory activity of some coumarin schiff base derivatives: In silico and in vitro study","volume":"16","author":"Hamid","year":"2022","journal-title":"Drug Des. Devel Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.5530\/jyp.2018.2s.2","article-title":"Synthesis, anti-inflammatory and antioxidant activity of mannich bases of dehydrozingerone derivatives","volume":"10","author":"Hayun","year":"2018","journal-title":"J. Young Pharm."},{"key":"B21","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/ardp.200900291","article-title":"Synthesis of 2-mercaptobenzimidazole derivatives as potential anti-microbial and cytotoxic agents","volume":"344","author":"Hosamani","year":"2011","journal-title":"Arch. Pharm. Weinh."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.3390\/app11041877","article-title":"Schiff bases: Interesting scaffolds with promising antitumoral properties","volume":"11","author":"Iacopetta","year":"2021","journal-title":"Appl. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/J.ARABJC.2010.12.025","article-title":"Synthesis of some Mannich base derivatives and their antimicrobial activity study","volume":"7","author":"Idhayadhulla","year":"2014","journal-title":"Arab. J. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.ejmech.2007.07.012","article-title":"Synthesis and antioxidant activity evaluation of new hexahydropyrimido[5,4-c]quinoline-2,5-diones and 2-thioxohexahydropyrimido[5,4-c]quinoline-5-ones obtained by Biginelli reaction in two steps","volume":"43","author":"Ismaili","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4103\/0975-8844.169745","article-title":"Role of antioxidants in facilitating the body functions: A review","volume":"7","author":"Kattappagari","year":"2015","journal-title":"J. Orofac. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1002\/jcb.23137","article-title":"Suppression of LPS-induced inflammatory and NF-\u03baB responses by anomalin in RAW 264.7 macrophages","volume":"112","author":"Khan","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1002\/jccs.202000161","article-title":"Synthesis, characterization, and antioxidant activity of heterocyclic Schiff bases","volume":"67","author":"Kizilkaya","year":"2020","journal-title":"J. Chin. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1080\/10942912.2014.986331","article-title":"Determination of the total antioxidant capacity and quantification of phenolic compounds of different solvent extracts of black mustard seeds (Brassica nigra)","volume":"18","author":"Lee","year":"2015","journal-title":"Int. J. Food Prop."},{"key":"B29","doi-asserted-by":"publisher","first-page":"118","DOI":"10.4103\/0973-7847.70902","article-title":"Free radicals, antioxidants and functional foods: Impact on human health","volume":"4","author":"Lobo","year":"2010","journal-title":"Pharmacogn. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"864286","DOI":"10.3389\/fmolb.2022.864286","article-title":"Triazoles and their derivatives: Chemistry, synthesis, and therapeutic applications","volume":"9","author":"Matin","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.sjbs.2015.09.005","article-title":"Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects","volume":"24","author":"Mistry","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12941-017-0228-7","article-title":"An assessment on the role of endophytic microbes in the therapeutic potential of Fagonia indica","volume":"16","author":"Rahman","year":"2017","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.bmcl.2015.01.010","article-title":"Schiff\u2019s bases of quinazolinone derivatives: Synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants","volume":"25","author":"Rakesh","year":"2015","journal-title":"Bioorg Med. Chem. Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"112358","DOI":"10.1016\/j.ejmech.2020.112358","article-title":"Indole chalcones: Design, synthesis, in vitro and in silico evaluation against Mycobacterium tuberculosis","volume":"198","author":"Ramesh","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3390\/vaccines9091012","article-title":"New 1,2,3-triazole scaffold schiff bases as potential anti-Covid-19: Design, synthesis, dft-molecular docking, and cytotoxicity aspects","volume":"9","author":"Said","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.ymeth.2007.01.006","article-title":"Microtitre plate-based antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals","volume":"42","author":"Sarker","year":"2007","journal-title":"Methods"},{"key":"B37","doi-asserted-by":"publisher","first-page":"24981","DOI":"10.1021\/acsomega.1c04016","article-title":"Design, synthesis, and in vitro and in vivo evaluation of novel fluconazole-based compounds with promising antifungal activities","volume":"6","author":"Shafiei","year":"2021","journal-title":"ACS Omega"},{"key":"B38","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3390\/ph14030224","article-title":"1,2,4-Triazoles as important antibacterial agents","volume":"14","author":"Strzelecka","year":"2021","journal-title":"Pharmaceuticals"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.3390\/cimb44090280","article-title":"Synthesis and antibacterial activity evaluation of biphenyl and dibenzofuran derivatives as potential antimicrobial agents against antibiotic-resistant bacteria","volume":"44","author":"Wang","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40199-017-0174-0","article-title":"Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents","volume":"25","author":"Waseem","year":"2017","journal-title":"DARU, J. Pharm. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"407","DOI":"10.7164\/antibiotics.55.407","article-title":"Identifying protein kinase inhibitors using an assay based on inhibition of aerial hyphae formation in Streptomyces","volume":"55","author":"Waters","year":"2002","journal-title":"J. Antibiot."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1590\/S0103-50532011000600018","article-title":"Citrinin derivatives from the soil filamentous fungus Penicillium sp. H9318","volume":"22","author":"Yao","year":"2011","journal-title":"J. Braz Chem. Soc."},{"key":"B43","doi-asserted-by":"publisher","first-page":"6","DOI":"10.7324\/JAPS.2019.90102","article-title":"Synthesis and anticancer activity of novel 2-phenylindole linked imidazolothiazole, thiazolo-s-triazine and imidazolyl-sugar systems","volume":"9","author":"Yousif","year":"2019","journal-title":"J. Appl. Pharm. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s12906-017-1951-5","article-title":"Polarity based characterization of biologically active extracts of Ajuga bracteosa Wall. ex Benth. and RP-HPLC analysis","volume":"17","author":"Zahra","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"113665","DOI":"10.1016\/j.ejmech.2021.113665","article-title":"Research progress of indole compounds with potential antidiabetic activity","volume":"223","author":"Zhu","year":"2021","journal-title":"Eur. J. Med. Chem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1084181\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T07:16:16Z","timestamp":1677482176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1084181\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":45,"alternative-id":["10.3389\/fphar.2023.1084181"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1084181","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]},"article-number":"1084181"}}