WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article Synthesis, Molecular Modeling, Anti-Cancer and COX-1/2 Inhibitory Activities of Novel Thiazolidinones Containing Benzothiazole Core(Bangladesh Pharmacological Society, 2024) Kulabas, Necla; Guven, Cansu Tamniku; Duracık, Merve; Bingol Ozakpinar, Ozlem; Küçükgüzel, İlkay; Ozakpinar, Ozlem BingolIn this study, new 1,3-thiazolidin-4-one derivatives containing arylmethylene groups in the 5-position were obtained from 6-(trifluoromethoxy)-1,3-benzo-thiazol-2-amine (riluzole). Synthesized compounds were characterized by spectral data and elemental analysis. In vitro, cytotoxic activities of the synthesized molecules were evaluated against the human lung cancer (A549) and human prostate cancer (PC-3) cell lines. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Ten target compounds 3-12 were also screened for their COX-1 and COX-2 inhibitory activities. Of these compounds, 4 showed the highest COX-2 inhibition at 10 μM. Molecular docking calculations were performed to understand the binding interactions of compounds with COX-1 and COX-2 proteins. In silico studies of the tested compounds represented important binding modes that may be responsible for their anti-cancer activity via selective inhibition of the COX-2 enzyme. ADMET predictions were conducted to assess the drug-like properties of the novel compounds. © 2024 Elsevier B.V., All rights reserved.Article The Effect of Vitamin D and Paricalcitol on Protein Disulfide Isomerase(Marmara University, 2025) Koksal, Murat; Şekerler, Turgut; Şener, Azize; Koksal, Muhammed MuratProtein disulfide isomerase (PDI), a multifunctional protein plays an important role as oxidoreductase, isomerase and chaperone in the cell. Prior studies have identified PDI is highly expressed in many different cancer types and presented as a new potential target for cancer treatment. Here, we investigated vitamin D and its analogue paricalcitol in silico interaction of the human PDI and inhibition of PDI reductase activity in vitro. We observed a non-covalent mechanism where the main skeleton of the vitamin D3 ans paricalcitol sturcture is located at the hydrophobic site in the b' domain of PDI and forms a hydrogen bond with a residue (His138) in tihs domain. They also form multiple weak hydrophobic interactions with various chemical groups of the b' subunit. For the first time, we demonstrate that 1,25-dihydroxyvitamin D3 (1a,25(OH)2 vitamin D3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79±1.43 nmol/L and 32.83±3.15 nmol/L respectively. The two compounds can also block the denistrosation activity of PDI.Article Citation - WoS: 2Citation - Scopus: 2Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents(John Wiley and Sons Inc, 2025) Poyraz Yılmaz, P.; Kulabaş, N.; Bozdeveci, A.; Vagolu, S.K.; Imran, M.; Tatar, E.; Küçükgüzel, İ.; Yilmaz, Pinar PoyrazTwenty azole-fluoroquinolone hybrids were designed and synthesized by conjugating thiazole and thiadiazole structures to ciprofloxacin and norfloxacin via a 2-oxoethyl bridge. The structures and purities of the synthesized compounds were proven by spectral techniques. The antimycobacterial effects of target compounds 21–40 were tested against Mycobacterium tuberculosis H37Rv strain. Among the 20 synthesized compounds, 12 exhibited minimal inhibition concentration (MIC) values in the range of 1.56–25 μg/mL. Among the molecules screened for antimycobacterial effects, the most effective was compound 35, a thiadiazole-ciprofloxacin hybrid. The cytotoxic effect of this molecule was found to be lower than the reference drugs, and it was also determined to be a more effective inhibitor than ciprofloxacin and norfloxacin in the DNA-gyrase supercoiling test. The antimicrobial effects of compounds 21–40 were screened by agar-well diffusion and microdilution tests against Gram-positive/negative bacteria, a fast-growing mycobacterium, and two yeast strains. While most of the compounds tested showed antibacterial effects, the most effective fluoroquinolone derivative appeared to be compound 31 with an MIC value of < 0.63 μg/mL against all Gram-negative bacteria tested. Azole-fluoroquinolone hybrids 21–40 did not show any activity against non-pathogenic Lactobacillus species and yeast-like fungi, indicating that they have selective antibacterial and antimycobacterial activity, particularly against Gram-negative bacteria. In silico molecular docking studies were conducted to uncover the interactions between lead compound 35 and the DNA gyrase proteins of M. tuberculosis and S. aureus. Additionally, a 100 ns molecular dynamics simulation was carried out to assess the stability of the complexes formed between compound 35 and both proteins. © 2025 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.Article The Effect of Vitamin D and Paricalcitol on Protein Disulfide Isomerase(Marmara Univ, Fac Pharmacy, 2024) Koksal, Muhammed Murat; Sekerler, Turgut; Sener, AzizeProtein disulfide isomerase (PDI), a multifunctional protein plays an important role as oxidoreductase, isomerase and chaperone in the cell. Prior studies have identified PDI is highly expressed in many different cancer types and presented as a new potential target for cancer treatment. Here, we investigated vitamin D and its analogue paricalcitol in silico interaction of the human PDI and inhibition of PDI reductase activity in vitro. We observed a non-covalent mechanism where the main skeleton of the vitamin D3 and paricalcitol structure is located at the hydrophobic site in the b' domain of PDI and forms a hydrogen bond with a residue (His138) in this domain. They also form multiple weak hydrophobic interactions with various chemical groups of the b' subunit. For the first time, we demonstrate that 1,25dihydroxyvitamin D3 (1 alpha,25(OH)2 vitamin D3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79 +/- 1.43 nmol/L and 32.82 +/- 3.15 nmol/L respectively. The two compounds can also block the denitrosation activity of PDI.Article Citation - WoS: 1Citation - Scopus: 1In Silico Evaluation of H1-Antihistamine as Potential Inhibitors of SARS-CoV RNA-Dependent RNA Polymerase: Repurposing Study of COVID-19 Therapy(Turkish Pharmacists Association, 2024) Küçükgüzel, İlkay; Kulabaş, Necla; Hamdan, MazınIntroduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), from the family Coronaviridae, is the seventh known coronavirus to infect humans and cause acute respiratory syndrome. Although vaccination efforts have been conducted against this virus, which emerged in Wuhan, China, in December 2019 and has spread rapidly around the world, the lack of an Food and Drug Administration-approved antiviral agent has made drug repurposing an important approach for emergency response during the COVID-19 pandemic. The aim of this study was to investigate the potential of H1-antihistamines as antiviral agents against SARS-CoV-2 RNA-dependent RNA polymerase enzyme. Materials and Methods: Using molecular docking techniques, we explored the interactions between H1-antihistamines and RNA-dependent RNA polymerase (RdRp), a key enzyme involved in viral replication. The three-dimensional structure of 37 H1-antihistamine molecules was drawn and their energies were minimized using Spartan 0.4. Subsequently, we conducted a docking study with Autodock Vina to assess the binding affinity of these molecules to the target site. The docking scores and conformations were then visualized using Discovery Studio. Results: The results examined showed that the docking scores of the H1-antihistamines were between 5.0 and 8.3 kcal/mol. These findings suggested that among all the analyzed drugs, bilastine, fexofenadine, montelukast, zafirlukast, mizolastine, and rupatadine might bind with the best binding energy (< -7.0 kcal/mol) and inhibit RdRp, potentially halting the replication of the virus. Conclusion: This study highlights the potential of H1-antihistamines in combating COVID-19 and underscores the value of computational approaches in rapid drug discovery and repurposing efforts. Finally, experimental studies are required to measure the potency of H1-antihistamines before their clinical use against COVID-19 as RdRp inhibitors.Article Citation - WoS: 7Citation - Scopus: 5Synthesis and Evaluation of Novel Metacetamol Derivatives With Hydrazone Moiety as Anticancer and Antimicrobial Agents(Wiley-v C H verlag Gmbh, 2023) Senkardes, Sevil; Atlihan, Irem; Cayir, Elif; Tiber, Pinar Mega; Orun, Oya; Nigiz, Seyma; Kucukguzel, S. Guniz; Mega Tiber, PınarBy exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, H-1 and C-13-NMR, and mass spectroscopic methods. The obtained molecules (3 a-j) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide (3 e) was found to be the most effective derivative with an IC50 value of 9.89 & mu;M against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 & mu;g/ml), indicating that nitro group at the 4(th) position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.Article Citation - WoS: 13Citation - Scopus: 14Synthesis, Antimicrobial Evaluation and Molecular Modeling Studies of Novel Thiosemicarbazides/Semicarbazides Derived From <i>p</I>-aminobenzoic Acid(Elsevier, 2022) Han, M. Ihsan; Ince, Ufuk; Gunduz, Miyase Gozde; Coskun, G. Pelin; Birgul, Kaan; Dogan, Senguel Dilem; Kucukguzel, S. Guniz; İhsan Han, M.The development of novel antimicrobial agents is critical to combat life-threatening drug-resistant bacterial and fungal pathogens. In the present study, a new series of p-aminobenzoic acid (PABA) derivatives carrying thiosemicarbazide/semicarbazide moiety were designed, synthesized, and studied for their antimicrobial activity. The target molecules (3a-f, 4a-f) were achieved by the reaction of 4aminobenzohydrazide, obtained from PABA, and various phenyl isothiocyanates/isocyanates. Following structural characterization by spectroscopic methods (H-1 NMR, C-13 NMR, FT-IR, and LC-MS analyses), the synthesized compounds were tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and their clinical isolates. Thiosemicarbazides with lipophilic substituents on the phenyl ring were identified as the most active compounds in this series. Among the studied molecules, compound 3e, thiosemicarbazide derivative with trifluoromethyl groups on the phenyl moiety, showed the best antimicrobial activity. Physicochemical parameters of the compounds were computed to predict the drug-likeness of the title compounds. Finally, molecular docking studies were performed in the allosteric binding pocket of ?-alanine: ?-alanine ligase (Ddl) to explain the potential antibacterial activity mechanism of 3e against S. aureus strains . (C) 2022 Elsevier B.V. All rights reserved.Article Citation - WoS: 6Citation - Scopus: 6Synthesis, Antimicrobial Properties and <i>in Silico</I> Studies of Aryloxyacetic Acid Derivatives With Hydrazone or Thiazolidine-4 Scaffold(Taylor & Francis inc, 2023) Senkardes, Sevil; Kart, Didem; Bebek, Bilge; Gunduz, Miyase Gozde; Kucukguzel, S. GunizIn this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 mu g/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains. Communicated by Ramaswamy H. Sarma