title: Diclofenac-Based Hydrazones and Spirothiazolidinones: Synthesis, Characterization, and Antimicrobial Properties.
abstract: We report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a-f) and spirothiazolidinone (5a-f, 6a-f) derivatives designed as potential antimicrobial agents. The compounds were evaluated in vitro for their antiviral activity against a wide spectrum of DNA and RNA viruses. They were further screened in vitro against different strains of bacteria and fungi. The hydrazone derivatives, 4a and 4c-f, were found to be active against herpesviruses (HSV-1, HSV-2, and HSV-1 TK-), vaccinia virus, and Coxsackie B4 virus, with EC50values between 6.6 µg/mL and 14.7 μg/mL, and the selectivity index values were greater than 10 for 4a and 4f. The newly synthesized compounds (4-6) were inactive against the bacterial and the fungal strains tested, at levels below 2500, 1250, or 625 μg/mL. Interestingly, the key intermediate 3 with a free hydrazide moiety displayed antifungal properties against Candida albicans and C. parapsilosis at MIC values of 4.88 µg/mL and 78.12 μg/mL, respectively.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul University, Istanbul, Turkey.
authors.forename: Ayşe
authors.initials: A
authors.lastname: Kocabalkanlı
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul University, Istanbul, Turkey.
authors.forename: Gökçe
authors.identifier: http://orcid.org/0000-0003-0516-6010
authors.initials: G
authors.lastname: Cihan-Üstündağ
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Istanbul University, Istanbul, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Mataracı-Kara
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul University, Istanbul, Turkey.
authors.forename: Mebble
authors.initials: M
authors.lastname: Nassozi
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul University, Istanbul, Turkey.
authors.forename: Gültaze
authors.initials: G
authors.lastname: Çapan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000187:drug effects; D006367:HeLa Cells; D006564:Herpesviridae / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061985:Madin Darby Canine Kidney Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000890:Anti-Infective Agents; D006835:Hydrazones; D013141:Spiro Compounds; D053778:Thiazolidines; D004008:Diclofenac
keywords: Antimicrobial activity; Cytotoxic activity; Rational drug design; Structure elucidation; Synthesis