Browsing by Author "Karali, Nilgun"

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5-fluoro/(trifluoromethoxy)-2-indolinone Derivatives With Anti-Interleukin Activity
(Wiley-v C H verlag Gmbh, 2023) Soylu-Eter, Ozge; Sevincli, Zekiye Seyma; Ersoy, Betul; Hasanusta, Bahar; Gatfar, Ugur; Lack, Nathan A.; Karali, Nilgun
The pro-inflammatory cytokine interleukin-1 (IL-1) drives the pathogenesis of several inflammatory diseases. Recent studies have revealed that 2-indolinones can modulate cytokine responses. Therefore, we screened several 2-indolinone derivatives in preliminary studies to develop agents with anti-IL-1 activity. First, the putative efficacies and binding interactions of 2-indolinones were evaluated by docking studies. Second, previously synthesized 5-fluoro/(trifluoromethoxy)-1H-indole-2,3-dione 3-(4-phenylthiosemicarbazones) (compounds 47-69) which had the highest inhibitory effect in the screening were evaluated for inhibitory effects on the IL-1 receptor (IL-1R). Compounds 52 (IC50 = 0.09 mu M) and 65 (IC50 = 0.07 mu M) were selected as lead compounds for the subsequent synthesis of new derivatives. The novel 5-fluoro/(trifluoromethoxy)-1H-indole-2,3-dione 3-(4-phenylthiosemicarbazones) (compounds 70-116) were designed, synthesized, and in vitro studies were completed. The compounds 76, 78, 81, 91, 100, 105, and 107 tested showed nontoxic inhibitory effects on IL-1R-dependent responses in the range of 0.01-0.06 mu M and stronger than the lead compounds 52 and 65. In vitro and in silico findings showed that compounds 78 (IC50 = 0.01 mu M) and 81 (IC50 = 0.02 mu M) had the strongest IL-1R inhibitory effects and the most favorable drug-like properties. Molecular modeling studies of the compounds 78 and 81 were carried out to determine the possible binding interactions at the active site of the IL-1R. Novel 5-fluoro/(trifluoromethoxy)-2-indolinone derivatives were designed and synthesized based on in silico and preliminary in vitro test results from lead compounds. All compounds tested displayed nontoxic IL-1 receptor inhibitory effects at IC50 values in the range of 10 nM to 13 mu M, and seven compounds showed inhibitory responses stronger than the lead compounds at 0.01-0.06 mu M.image
Anticancer and Antituberculosis Effects of 5-Fluoro 3-Thiosemicarbazones
(Istanbul Univ, Fac Pharmacy, 2020) Sevincli, Zekiye Seyma; Canturk, Zerrin; Dikmen, Miris; Karali, Nilgun
Background and Aims: The aim of this study was to screen the in vitro anticancer/antituberculosis activities of 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-thiosemicarbazones. Methods: A549/U-87MG cell Lines were used for the anticancer activity of the compounds, while CCD-19Lu cell Line was used to determine their cytotoxic effects. In antituberculosis activity studies using MTB H37Rv cell line, BJ cell line was used to determine the cytotoxic effects. MTT assay was used to obtain IC50 values. Results: 6a, 6b, 6g, 6h, 6l, 6n, 7c, 7k and 7l were found to be highly effective against A549 cell line compared to cisplatin whereas 6d, 6h, 6l, 6n, 7d and 7f were found to be effective against U-87MG cell Line compared to cisplatin. It was also determined that 6a, 6b and 7l did not show cytotoxic effects on CCD-19Lu cell line. The antituberculosis effects of the compounds were investigated against MTB H37Rv cell groups using rifampicin as standard. It was determined that 6b, 6c, 6g-k, 6n, 7b, 7j and it have near-standard activity and 6b, 7b and 7l were not cytotoxic on BJ cell line. Conclusion: While determining effective compounds in anticancer studies, it was concluded that active compounds can be reached by modifications in compounds in antituberculosis studies.
Synthesis, Molecular Modeling and Antiviral Activity of Novel 5-Fluoro 3-Thiosemicarbazones
(Academic Press inc Elsevier Science, 2020) Sevincli, Zekiye Seyma; Duran, Gizem Nur; Ozbil, Mehmet; Karali, Nilgun
In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACV(r) and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R-2 ethyl substituted 7 derivatives were found effective against viruses tested. R-1 4-CF3 substituted 7d, R-1 4-OCH3 substituted 7 g and R-1 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV. Whereas only R-1 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modeling studies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.