{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:34:09Z","timestamp":1791866049462,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Research Agency (AEI), Spanish Ministry of Science, Innovation and Universities","award":["PID2020-113558RB-C41"],"award-info":[{"award-number":["PID2020-113558RB-C41"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 6a\u2013e, 7a\u2013e, 8, 9, 10a and 10b in good yields. The in vitro antimicrobial activity of compounds 5a\u2013e, 6a\u2013e, 7a\u2013d, 8, 9, 10a and 10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds 5a, 5b, 5e, 5f, 6a\u2013e, 7a\u2013d, 8, 9, 10a and 10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds 5e, 6a\u2013e, 7a\u2013d and 10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC50 &lt; 25 \u03bcM). A detailed structural insight study based on the single crystals of compounds 5a, 5b, 6a, 6d and 10a is also reported. Molecular docking studies of the highly active antibacterial compounds 5e, 6b, 6d, 7a and 7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds 6d, 6e and 7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2).<\/jats:p>","DOI":"10.3390\/ph17091123","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T01:48:49Z","timestamp":1724636929000},"page":"1123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles"],"prefix":"10.3390","volume":"17","author":[{"given":"Nada A.","family":"El-Emam","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-756X","authenticated-orcid":false,"given":"Mahmoud B.","family":"El-Ashmawy","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-1021","authenticated-orcid":false,"given":"Ahmed A. 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Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.2174\/1568026620666200704140107","article-title":"1,2,4-Triazole: A privileged scaffold for the development of potent antifungal agents\u2014A brief review","volume":"20","author":"Tratrat","year":"2020","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.2165\/11596540-000000000-00000","article-title":"Triazole antifungal agents in invasive fungal infections: A comparative review","volume":"71","year":"2011","journal-title":"Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/jac\/dki473","article-title":"Fluconazole for the management of invasive candidiasis: Where do we stand after 15 years?","volume":"57","author":"Charlier","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1517\/17425255.2013.794785","article-title":"Itraconazole: An update on pharmacology and clinical use for treatment of invasive and allergic fungal infections","volume":"9","author":"Lestner","year":"2013","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s40262-015-0297-8","article-title":"Therapeutic drug monitoring of voriconazole in the management of invasive fungal infections: A critical review","volume":"54","author":"Elewa","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1345\/aph.1L005","article-title":"Posaconazole: An oral triazole with an extended spectrum of activity","volume":"42","author":"Rachwalski","year":"2008","journal-title":"Ann. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rathod, B., and Kumar, K. (2022). Synthetic and medicinal perspective of 1,2,4-triazole as anticancer agents. Chem. Biodivers., 19.","DOI":"10.1002\/cbdv.202200679"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.2174\/1568026620666200128143230","article-title":"Recent development of 1,2,4-triazole-containing compounds as anticancer agents","volume":"20","author":"Wen","year":"2020","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1038\/s41467-020-16061-7","article-title":"p85\u03b2 regulates autophagic degradation of AXL to activate oncogenic signaling","volume":"11","author":"Rao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s10549-018-05125-4","article-title":"Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive\/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up","volume":"174","author":"Rugo","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1023\/A:1013051107535","article-title":"Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea","volume":"70","author":"Knott","year":"2001","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1056\/NEJMoa1811714","article-title":"Overall survival with fulvestrant plus anastrozole in metastatic breast cancer","volume":"380","author":"Mehta","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1021\/jm4000566","article-title":"Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1\/2 inhibitor","volume":"56","author":"Voronkov","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115603","DOI":"10.1016\/j.ejmech.2023.115603","article-title":"Recent advances in 1,2,3- and 1,2,4-triazole hybrids as antimicrobials and their SAR: A critical review","volume":"259","author":"Tian","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Strzelecka, M., and \u015awi\u0105tek, P. (2021). 1,2,4-Triazoles as important antibacterial agents. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030224"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2000223","DOI":"10.1002\/ardp.202000223","article-title":"1,2,4-Triazole hybrids with potential antibacterial activity against methicillin-resistant Staphylococcus aureus","volume":"354","author":"Ge","year":"2021","journal-title":"Arch. Pharm. (Weinheim)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.4155\/fmc-2020-0295","article-title":"Advances in the application of 1,2,4-triazole-containing hybrids as anti-tuberculosis agents","volume":"13","author":"Cao","year":"2021","journal-title":"Future Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.coviro.2011.10.030","article-title":"Ribavirin for the treatment of chronic hepatitis C virus infection: A review of the proposed mechanisms of action","volume":"1","author":"Paeshuyse","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Aly, A.A., Hassan, A., Makhlouf, M.M., and Br\u00e4se, S. (2020). Chemistry and biological activities of 1,2,4-triazolethiones-antiviral and anti-infective drugs. Molecules, 25.","DOI":"10.3390\/molecules25133036"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1021\/tx500134g","article-title":"Bioactivation potential of thiophene-containing drugs","volume":"27","author":"Gramec","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2174\/1389557520666201202113333","article-title":"Diverse thiophenes as scaffolds in anti-cancer drug development: A concise review","volume":"21","author":"Bhilare","year":"2021","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ejmech.2017.09.039","article-title":"2-Aminothiophene scaffolds: Diverse biological and pharmacological attributes in medicinal chemistry","volume":"140","author":"Bozorov","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1021\/acs.molpharmaceut.7b00277","article-title":"Overexpression of ATP-binding cassette subfamily g member 2 confers resistance to phosphatidylinositol 3-kinase inhibitor PF-4989216 in cancer cells","volume":"14","author":"Wu","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1158\/0008-5472.CAN-05-2873","article-title":"OSI-930: A novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models","volume":"66","author":"Garton","year":"2006","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1158\/1078-0432.CCR-12-2258","article-title":"First-in-human phase I trial of two schedules of OSI-930, a novel multikinase inhibitor, incorporating translational proof-of-mechanism studies","volume":"19","author":"Yap","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1016\/j.bmc.2013.03.061","article-title":"Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 1","volume":"21","author":"Wang","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1128\/AAC.26.5.699","article-title":"Fungicidal activity of tioconazole in relation to growth phase of Candida albicans and Candida parapsilosis","volume":"26","author":"Beggs","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1093\/jac\/36.4.713","article-title":"In-vitro antifungal activity of sertaconazole, econazole, and bifonazole against Candida spp.","volume":"36","year":"1995","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/MEG.0000000000000084","article-title":"VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens for genotype 1 hepatitis C virus infection","volume":"26","author":"Sulkowski","year":"2014","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11178","DOI":"10.1039\/c3cp00054k","article-title":"Halogen bonding and other \u03c3 -hole interactions: A perspective","volume":"15","author":"Politzer","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/anie.201809432","article-title":"Chalcogen bonding: An overview","volume":"58","author":"Vogel","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Politzer, P., and Murray, J.S. (2017). \u03c3-Hole interactions: Perspectives and misconceptions. Crystals, 7.","DOI":"10.3390\/cryst7070212"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/jhet.5570130450","article-title":"Improved syntheses of 5-substituted-4-amino-3-mercapto-(4H)-1,3,4-triazoles","volume":"13","author":"Reid","year":"1976","journal-title":"J. Heterocycl. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.56431\/p-dzucwt","article-title":"Synthesis, characterization and antimicrobial activity of N\u2019-benzylidene-5-bromothiophene-2-carbohydrazide derivatives","volume":"14","author":"Makwana","year":"2014","journal-title":"Int. Lett. Chem. Phys. Astron."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejmech.2013.07.024","article-title":"Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2-aminomethyl-4-substituted-1,2,4-triazoline-3-thiones","volume":"68","author":"Alrashood","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22995","DOI":"10.3390\/ijms151222995","article-title":"Antimicrobial and hypoglycemic activities of novel N-Mannich bases derived from 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thiones","volume":"15","author":"Hassan","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","first-page":"505","article-title":"Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted and N-substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols","volume":"8","author":"Asiri","year":"2014","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s00044-012-0248-y","article-title":"Microbiologically active Mannich bases derived from 1,2,4-triazoles. The effect of C-5 substituent on antibacterial activity","volume":"22","author":"Plech","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"786","DOI":"10.3109\/14756366.2013.855926","article-title":"Synthesis, antiproliferative and antimicrobial activity of new Mannich bases bearing 1,2,4-triazole moiety","volume":"29","author":"Rzymowska","year":"2014","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/cbdd.12920","article-title":"Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies","volume":"89","author":"Kanazir","year":"2017","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Albelwi, F.F., Teleb, M., Abu-Serie, M.M., Moaty, M.N.A.A., Alsubaie, M.S., Zakaria, M.A., El Kilany, Y., Aouad, M.R., Hagar, M., and Rezki, N. (2021). Halting tumor progression via novel non-hydroxamate triazole-based Mannich bases mmp-2\/9 inhibitors; design, microwave-assisted synthesis, and biological evaluation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910324"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34506","DOI":"10.1021\/acsomega.2c04252","article-title":"Structural and energetic properties of weak noncovalent interactions in two closely related 3,6-disubstituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives: In vitro cyclooxygenase activity, crystallography, and computational investigations","volume":"7","author":"Karthikeyan","year":"2022","journal-title":"ACS Omega"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.molstruc.2019.01.106","article-title":"Insights into the nature of weak noncovalent interactions in 3-(4-fluorophenyl)-6-(2-fluorophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole, a potential bioactive agent: X-ray, QTAIM and molecular docking analysis","volume":"1183","author":"Akilandeswari","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_46","unstructured":"Wood, G.L., and Washington, J.A. (1995). Manual of Clinical Microbiology, American Society for Microbiology."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/jac\/48.suppl_1.5","article-title":"Determination of minimum inhibitory concentrations","volume":"48","author":"Andrews","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jac\/dkl393","article-title":"Bactericidal agents in the treatment of MRSA infections\u2014The potential role of daptomycin","volume":"58","author":"French","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1006\/abbi.1993.1311","article-title":"Characterisation of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): Subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction","volume":"303","author":"Berridge","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.2042-7158.2012.01567.x","article-title":"Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems","volume":"65","author":"Tacar","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy ofdocking with a new scoring function, efficientoptimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"W159","DOI":"10.1093\/nar\/gkac394","article-title":"CB-Dock2: Improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2310522120","DOI":"10.1073\/pnas.2310522120","article-title":"Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases","volume":"120","author":"Dunbar","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1023\/B:RUJO.0000044552.07729.40","article-title":"Synthesis of trifluoroalkyl- and fluoroaryl-substituted 4,5-dihydro-1H-1,2,4-triazole-5-thiones","volume":"40","author":"Sevenard","year":"2004","journal-title":"Russ. J. Org. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A complete structure solution, refinement and analysis program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"SHELXT\u2014Integrated space-group and crystal-structure determination","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. 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