{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:55Z","timestamp":1792804795573,"version":"4.5.0"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a\u2013d, pyridine-2-one 3\u201310, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 18.17\u201323.87 \u00b5M, and of DHFR, with IC50 values of 4.33\u20135.54 \u00b5M; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes. Finally, molecular docking and some AMED studies were performed.<\/jats:p>","DOI":"10.3390\/antibiotics10020162","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8542-7465","authenticated-orcid":false,"given":"Ahmed","family":"Ragab","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan A.","family":"Fouad","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Girls), Al-Azhar University, Nasr City, Cairo 11754, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola A. Abu","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Entsar M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Girls), Al-Azhar University, Nasr City, Cairo 11754, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Girls), Al-Azhar University, Nasr City, Cairo 11754, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-4634","authenticated-orcid":false,"given":"Ahmed A.","family":"Askar","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousry A.","family":"Ammar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1126\/science.270.5237.724","article-title":"Antibiotics That Resist Resistance","volume":"270","author":"Service","year":"1995","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1358\/dof.2009.34.2.1313642","article-title":"New approaches to overcoming bacterial resistance","volume":"34","author":"Fukuda","year":"2009","journal-title":"Drugs Future"},{"key":"ref_3","unstructured":"O\u2019Neill, J. (2020, October 21). Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Available online: https:\/\/www.who.int\/antimicrobial-resistance\/news\/amr-newsletter-no13-july2016.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/infdis\/jix211","article-title":"White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs","volume":"216","author":"Boucher","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1016\/j.tet.2015.09.069","article-title":"Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics","volume":"72","author":"Maxson","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111814","DOI":"10.1016\/j.ejmech.2019.111814","article-title":"Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa","volume":"185","author":"Kim","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bcp.2016.09.025","article-title":"Antibiotics in late clinical development","volume":"133","author":"Fernandes","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1021\/jacs.8b02461","article-title":"Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics","volume":"140","author":"McCarthy","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103841","DOI":"10.1016\/j.bioorg.2020.103841","article-title":"Antimicrobial evaluation of thiadiazino and thiazolo quinoxaline hybrids as potential DNA gyrase inhibitors; design, synthesis, characterization and morphological studies","volume":"99","author":"Ammar","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ejmech.2014.08.016","article-title":"Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds","volume":"85","author":"Ibrahim","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1517\/13543784.2014.848853","article-title":"Combating multidrug-resistant Gram-negative bacterial infections","volume":"23","author":"Xu","year":"2014","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111825","DOI":"10.1016\/j.ejmech.2019.111825","article-title":"Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms","volume":"185","author":"Smirnov","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.ejmech.2018.06.061","article-title":"Design, synthesis, antiproliferative activity, molecular docking and cell cycle analysis of some novel (morpholinosulfonyl) isatins with potential EGFR inhibitory activity","volume":"156","author":"Ammar","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bioorg.2019.01.016","article-title":"Design, synthesis, molecular docking and biological activity evaluation of some novel indole derivatives as potent anticancer active agents and apoptosis inducers","volume":"85","author":"Ammar","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.bmc.2008.12.035","article-title":"Carbonic anhydrase inhibitors: Inhibition of the \u03b2-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates","volume":"17","author":"Isik","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.bmc.2005.09.037","article-title":"Synthesis and biological evaluation of N-(7- indazolyl) benzenesulfonamide derivatives as potent cell cycle inhibitors","volume":"14","author":"Bouissane","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1248\/cpb.58.160","article-title":"Sulfonamide-1,2,4-thiadiazole Derivatives as Antifungal and Antibacterial Agents: Synthesis, Biological Evaluation, Lipophilicity, and Conformational Studies","volume":"58","author":"Camoutsis","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1021\/jm030912m","article-title":"Unexpected Nanomolar Inhibition of Carbonic Anhydrase by COX-2-Selective Celecoxib: New Pharmacological Opportunities Due to Related Binding Site Recognition","volume":"47","author":"Weber","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.21608\/absb.2018.33767","article-title":"Synthesis, spectral characterization and pharmacological evaluation of novel thiazole-oxoindole hybrid compounds as potential anticancer agents","volume":"29","author":"Ammar","year":"2018","journal-title":"Al-Azhar Bull. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1021\/jm960803q","article-title":"Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors: Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-58635, Celecoxib)","volume":"40","author":"Penning","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3906\/kim-1307-38","article-title":"Application of guanidine and its salts in multicomponent reactions","volume":"38","author":"Rahimifard","year":"2014","journal-title":"Turkish J. Chem."},{"key":"ref_22","first-page":"1026","article-title":"Guanidine Group: Definition and Pharmaceutical Applications","volume":"7","author":"Khalaf","year":"2016","journal-title":"Res. J. Pharm. Biol. Chem. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11698","DOI":"10.1021\/bi011208f","article-title":"An Unusually Low pKa for Cys282 in the Active Site of Human Muscle Creatine Kinase","volume":"40","author":"Wang","year":"2001","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1089\/dna.2012.1926","article-title":"Metformin Synergistically Enhances Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin a against Osteosarcoma Cell Line","volume":"32","author":"Duo","year":"2013","journal-title":"DNA Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6782","DOI":"10.1016\/j.bmc.2007.08.005","article-title":"Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b] pyridines and thieno[2,3-b] pyridines","volume":"15","author":"Bahekar","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jhin.2006.01.024","article-title":"In vitro antimicrobial activity of the novel polymeric guanidine Akacid plus","volume":"63","author":"Kratzer","year":"2006","journal-title":"J. Hosp. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1016\/j.bmcl.2006.07.037","article-title":"Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug-resistant Gram-positive pathogens identified from a mixture-based combinatorial library","volume":"16","author":"Hensler","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","first-page":"377","article-title":"Hydroxyzine, cimetidine and vitamin C in reducing skin flap necrosis in ischemia-reperfusion injury in rats. A comparative study","volume":"17","author":"Georgopoulos","year":"2012","journal-title":"J. BU ON. Off. J. Balk. Union Oncol."},{"key":"ref_29","first-page":"710","article-title":"The specific inhibition of HepG2 cells proliferation by apoptosis induced by gabexate mesilate","volume":"3","author":"Ozeki","year":"2010","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1097\/00005344-198406060-00026","article-title":"Calcium channel modulation: Ability to inhibit or promote calcium influx resides in the same dihydropyridine molecule","volume":"6","author":"Thomas","year":"1984","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0223-5234(00)00103-3","article-title":"4-Aminopyridine derivatives with antiamnesic activity##Presented in part at the Italian\u2013Hungarian\u2013Polish Joint Meeting on Medicinal Chemistry, Giardini Naxos\u2013Taormina, September 28th\u2013October 1st 1999","volume":"35","author":"Andreani","year":"2000","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/hc.10019","article-title":"Naproxen in heterocyclic chemistry: Novel syntheses of triazoles, triazolothiadiazines, triazolothiadiazoles, and triazolothiadiazepine bearing an asymmetric carbon atom and radiostability of the biologically active compounds","volume":"13","author":"Ammar","year":"2002","journal-title":"Heteroat. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ejmech.2014.07.052","article-title":"Design, synthesis, antimicrobial evaluation and molecular docking studies of some new thiophene, pyrazole and pyridone derivatives bearing sulfisoxazole moiety","volume":"84","author":"Nasr","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"126926","DOI":"10.1016\/j.molstruc.2019.126926","article-title":"N-alkyl 2-pyridone versus O-alkyl 2-pyridol: Ultrasonic synthesis, DFT, docking studies and their antimicrobial evaluation","volume":"1199","author":"Hagar","year":"2020","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.1016\/j.bmcl.2017.10.006","article-title":"4-Hydroxy-2-pyridones: Discovery and evaluation of a novel class of antibacterial agents targeting DNA synthesis","volume":"27","author":"Arnold","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/1098-1128(200007)20:4<231::AID-MED1>3.0.CO;2-N","article-title":"The 2-pyridone antibacterial agents: Bacterial topoisomerase inhibitors","volume":"20","author":"Li","year":"2000","journal-title":"Med. Res. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.02609-16","article-title":"Activity of Delafloxacin against Contemporary Bacterial Pathogens from the United States and Europe, 2014","volume":"61","author":"Pfaller","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1021\/cr030101q","article-title":"Bacterial topoisomerase inhibitors: Quinolone and pyridone antibacterial agents","volume":"105","author":"Mitscher","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.arabjc.2013.11.026","article-title":"Cyanoacetanilides intermediates in heterocyclic synthesis. Part 6: Preparation of some hitherto unknown 2-oxopyridine, bipyridine, isoquinoline and chromeno[3,4-c] pyridine containing sulfonamide moiety","volume":"7","author":"Ammar","year":"2014","journal-title":"Arab. J. Chem."},{"key":"ref_40","first-page":"259","article-title":"Cyanoacetamide derivatives as synthons in heterocyclic synthesis","volume":"32","author":"Fadda","year":"2008","journal-title":"Turkish J. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104164","DOI":"10.1016\/j.bioorg.2020.104164","article-title":"Design, synthesis, antimicrobial activity and molecular docking studies of some novel di-substituted sulfonylquinoxaline derivatives","volume":"104","author":"Ammar","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s11164-017-3114-1","article-title":"Sulfonamides and carbamates of 3-fluoro-4-morpholinoaniline (linezolid intermediate): Synthesis, antimicrobial activity and molecular docking study","volume":"44","author":"Janakiramudu","year":"2018","journal-title":"Res. Chem. Intermed."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hussein, E.M., Al-Rooqi, M.M., Abd El-Galil, S.M., and Ahmed, S.A. (2019). Design, synthesis, and biological evaluation of novel N4-substituted sulfonamides: Acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors. BMC Chem., 13.","DOI":"10.1186\/s13065-019-0603-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112268","DOI":"10.1016\/j.ejmech.2020.112268","article-title":"Dihydrofolate reductase inhibitors for use as antimicrobial agents","volume":"195","author":"He","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","first-page":"99","article-title":"The immune system","volume":"88","author":"Parham","year":"2015","journal-title":"Yale J. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jang, M., Lim, T.-G., Ahn, S., Hong, H.-D., Rhee, Y.K., Kim, K.-T., Lee, E., Lee, J.H., Lee, Y.J., and Jung, C.S. (2016). Immune-enhancing effects of a high molecular weight fraction of Cynanchum wilfordii Hemsley in macrophages and immunosuppressed mice. Nutrients, 8.","DOI":"10.3390\/nu8100600"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103942","DOI":"10.1016\/j.jff.2020.103942","article-title":"Immunoenhancement effect of crude polysaccharides of Helvella leucopus on cyclophosphamide-induced immunosuppressive mice","volume":"69","author":"Zhang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103420","DOI":"10.1016\/j.jff.2019.103420","article-title":"Immunomodulatory effects of collagen hydrolysates from yak (Bos grunniens) bone on cyclophosphamide-induced immunosuppression in BALB\/c mice","volume":"60","author":"Gao","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/08923970600815139","article-title":"Aqueous Extract of Rhodiola imbricata Rhizome Stimulates Proinflammatory Mediators via Phosphorylated I\u03baB and Transcription Factor Nuclear Factor-\u03baB","volume":"28","author":"Mishra","year":"2006","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"415102","DOI":"10.1088\/0957-4484\/20\/41\/415102","article-title":"Immunostimulatory properties and enhanced TNF-\u03b1 mediated cellular immunity for tumor therapy by C60 (OH) 20 nanoparticles","volume":"20","author":"Liu","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"128966","DOI":"10.1016\/j.molstruc.2020.128966","article-title":"Novel adamantane-pyrazole and hydrazone hybridized: Design, synthesis, cytotoxic evaluation, SAR study and molecular docking simulation as carbonic anhydrase inhibitors","volume":"1223","author":"Wassel","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_52","first-page":"37","article-title":"Antiviral Activity Of Adamantane-Pyrazole Derivatives Against Foot And Mouth Disease Virus Infection In Vivo And In Vitro With Molecular Docking Study","volume":"5","author":"Ragab","year":"2020","journal-title":"J. Appl. Vet. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.tetlet.2015.11.098","article-title":"Transmonocyanoacetylation of phenylenediamines: A simple and efficient synthesis of novel N-(aminophenyl)-2-cyanoacetamides and their derivatives","volume":"57","author":"Ammar","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1515\/hc-2013-0032","article-title":"Cyanoacetanilide intermediates in heterocyclic synthesis. Part 7: Preparation of some spiro [indoline-3, 4\u2032-pyridine] and chromeno [3, 4-c] pyridine derivatives","volume":"19","author":"Ammar","year":"2013","journal-title":"Heterocycl. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/ardp.200600017","article-title":"Novel Pirfenidone Analogues: Synthesis of Pyridin-2-ones for the Treatment of Pulmonary Fibrosis","volume":"339","author":"Ammar","year":"2006","journal-title":"Arch. Pharm. (Weinheim)."},{"key":"ref_56","first-page":"893","article-title":"Facile and convenient synthesis of pyrimidine, 4H-3, 1-benzoxazin-4-one, pyrazolo [5, 1-b] quinazoline, pyrido [1, 2-a] quinazoline, and chromeno [3\u2019, 4\u2019: 4, 5] pyrido [1, 2-a] quinazoline derivatives","volume":"35","author":"AMMAR","year":"2011","journal-title":"Turkish J. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1007\/s13738-020-01944-9","article-title":"Design, synthesis, biological evaluation and molecular docking study based on novel fused pyrazolothiazole scaffold","volume":"17","author":"Rizk","year":"2020","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5155\/eurjchem.8.1.76-81.1542","article-title":"Synthesis and characterization of new imidazolidineiminothione and bis-imidazolidineiminothione derivatives as potential antimicrobial agents","volume":"8","author":"Ammar","year":"2017","journal-title":"Eur. J. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103951","DOI":"10.1016\/j.bioorg.2020.103951","article-title":"In vitro cytotoxic activity of thiazole-indenoquinoxaline hybrids as apoptotic agents, design, synthesis, physicochemical and pharmacokinetic studies","volume":"100","author":"Fayed","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1515\/znb-2016-0054","article-title":"New 1,3-diaryl-5-thioxo-imidazolidin-2,4-dione derivatives: Synthesis, reactions and evaluation of antibacterial and antifungal activities","volume":"71","author":"Abbas","year":"2016","journal-title":"Zeitschrift fur Naturforsch. Sect. B J. Chem. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"103619","DOI":"10.1016\/j.bioorg.2020.103619","article-title":"Design, synthesis, in vitro antimicrobial evaluation and molecular docking studies of indol-2-one tagged with morpholinosulfonyl moiety as DNA gyrase inhibitors","volume":"96","author":"Salem","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hassan, A.S., Askar, A.A., Naglah, A.M., Almehizia, A.A., and Ragab, A. (2020). Discovery of New Schiff Bases Tethered Pyrazole Moiety: Design, Synthesis, Biological Evaluation, and Molecular Docking Study as Dual Targeting DHFR\/DNA Gyrase Inhibitors with Immunomodulatory Activity. Molecules, 25.","DOI":"10.3390\/molecules25112593"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"466","DOI":"10.2174\/1570179412666150817221755","article-title":"New imidazolidineiminothione, imidazolidin-2-one and imidazoquinoxaline derivatives: Synthesis and evaluation of antibacterial and antifungal activities","volume":"13","author":"Ammar","year":"2016","journal-title":"Curr. Org. Synth."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2018.06.050","article-title":"Synthesis and antimicrobial evaluation of amino sugar-based naphthoquinones and isoquinoline-5,8-diones and their halogenated compounds","volume":"156","author":"Dias","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"111977","DOI":"10.1016\/j.ejmech.2019.111977","article-title":"European Journal of Medicinal Chemistry One-pot synthesis and molecular docking of some new spiropyranindol-2-one derivatives as immunomodulatory agents and in vitro antimicrobial potential with DNA gyrase inhibitor","volume":"188","author":"Salem","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.bmc.2019.02.024","article-title":"Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action","volume":"27","author":"Cai","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_67","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2020, October 21). M07-A10 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard\u2014Tenth Edition. Available online: https:\/\/clsi.org\/media\/1632\/m07a10_sample.pdf."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/ptr.990","article-title":"In vitro Immunomodulatory activity of verbascoside from Nepeta ucrainica L.","volume":"16","author":"Akbay","year":"2002","journal-title":"Phyther. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ayeka, P.A., Bian, Y., Githaiga, P.M., and Zhao, Y. (2017). The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-2030-7"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.intimp.2005.02.020","article-title":"Macrophage activation by polysaccharide isolated from Astragalus membranaceus","volume":"5","author":"Lee","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.intimp.2007.10.006","article-title":"Macrophage immunomodulatory activity of polysaccharides isolated from Glycyrrhiza uralensis fish","volume":"8","author":"Cheng","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.foodchem.2012.08.090","article-title":"Immunomodulatory effect of Ganoderma atrum polysaccharide on CT26 tumor-bearing mice","volume":"136","author":"Zhang","year":"2013","journal-title":"Food Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/ptr.1938","article-title":"The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans","volume":"20","author":"Brush","year":"2006","journal-title":"Phyther. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102968","DOI":"10.1016\/j.bioorg.2019.102968","article-title":"Synthesis and evaluation of Quinoline-3-carbonitrile derivatives as potential antibacterial agents","volume":"88","author":"Khan","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ejmech.2019.04.046","article-title":"dithioloquinolinethiones as new potential multitargeted antibacterial and antifungal agents: Synthesis, biological evaluation and molecular docking studies","volume":"175","author":"Kartsev","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1007\/s00044-017-1990-y","article-title":"Synthesis and biological evaluation of pyrazolo[1,5-a] pyrimidine-3-carboxamide as antimicrobial agents","volume":"26","author":"Hassan","year":"2017","journal-title":"Med. Chem. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ejmech.2018.04.045","article-title":"Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors","volume":"152","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.3390\/molecules15085162","article-title":"Characterization of Destrins with Different Dextrose Equivalents","volume":"15","author":"Sun","year":"2010","journal-title":"Molecules"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1093\/jac\/dkr247","article-title":"Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics","volume":"66","author":"Alt","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/ptr.1068","article-title":"In vitro immunomodulatory activity of flavonoid glycosides from Urtica dioica L.","volume":"17","author":"Akbay","year":"2003","journal-title":"Phyther. Res."},{"key":"ref_81","unstructured":"(2020, October 21). The Twinned 3.35A Structure of S. Aureus Gyrase Complex with Ciprofloxacin and DNA. Available online: https:\/\/www.rcsb.org\/structure\/2XCT."},{"key":"ref_82","unstructured":"(2020, October 21). Methotrexate-Resistant Variants of Human Dihydrofolate Reductase with Substitution of Leucine 22: Kinetics, Crystallography and Potential as Selectable Markers. Available online: https:\/\/www.rcsb.org\/structure\/1DLS."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:19:53Z","timestamp":1760159993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["antibiotics10020162"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10020162","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}