Person: KULABAŞ, NECLA
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
KULABAŞ
First Name
NECLA
Name
19 results
Search Results
Now showing 1 - 10 of 19
Publication Metadata only Novel fluoroquinolones containing 2-arylamino-2-oxoethyl fragment: Design, synthesis, evaluation of antibacterial and antituberculosis activities and molecular modeling studies(WILEY, 2022) TÜRE, ASLI; Kulabas, Necla; Ture, Asli; Bozdeveci, Arif; Krishna, Vagolu Siva; Karaoglu, Sengul Alpay; Sriram, Dharmarajan; Kucukguzel, IlkayNovel substituted fluoroquinolone derivatives, compounds 6-20 were designed, synthesized, and evaluated for antituberculosis and antibacterial activity. Antibacterial activities of the compounds were determined and compound 14 was found to be the most potent antimicrobial agent owing to minimal inhibitory concentration (MIC) value of <1.16 mu g/mu l for all tested bacteria. Further, compounds were tested in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Most of the compounds showed antimycobacterial effects with 1.56-25.00 mu g/ml MIC values. Compounds 14 and 18 were found to be the most active derivatives due to their MIC at 1.56 mu g/ml. Selected compounds 11, 14, 17, and 18 were tested for M. tuberculosis DNA supercoiling assay and they had IC50 values within a range of 6.35-15 mu M. Mechanism of binding to DNA gyrase enzymes was evaluated using in silico molecular modeling studies and it was shown that compounds 6-20 adopt a similar binding mode as already known for fluoroquinolone drugs.Publication Open Access Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors - an in silico docking and ADMET simulation study(MARMARA UNIV, 2021) KÜÇÜKGÜZEL, İLKAY; Kulabas, Necla; Yesil, Tugce; Kucukguzel, IlkayThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is characterized by a wide range of symptoms including fever, dry cough, headache, decreased sense of taste and smell, was first identified in Wuhan, China in December 2019. Currently, the nucleoside analog, remdesivir has been approved for emergency use authorization (EUA) by the regulatory agencies for the treatment of COVID-19 patients. The need for new antiviral agents has been continuing due to the some disadvantages of remdesivir. Molnupiravir (MLN) that is developed for the treatment of hepatitis C virus (HCV), have been reported to show antiviral activity against SARS-CoV-2 according to the results of a high throughput screen of nucleoside analogs and also phase II/III clinical trials of MLN is ongoing. In this study, fifty four MLN analogs (twelve of them are found to be reported in the literature whereas forty two of them are novel molecules) against SARS-CoV-2 RdRp were designed and evaluated for their potential antiviral activity by using molecular modelling studies. While among the designed MLN analogs, compound C17 was found to have the best potential inhibitor with-7.3 kcal/mol binding energy that is higher than molnupiravir and its active form EIDD-1931. Therefore, the isobutyric acid ester and monophosphate forms of C17 were also compared to the related MLN derivatives in terms of active site interactions. Lastly, the ten compounds with the best binding affinity including C17 were tested in silico for bioavailability, drug-likeness, ADME and safety profiles and were found to exhibit similar bioavailability and safety profile to MLN.Publication Metadata only Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors(SPRINGER, 2020) KÜÇÜKGÜZEL, İLKAY; Senkardes, Sevil; Han, M. Ihsan; Kulabas, Necla; Abbak, Muruvvet; Cevik, Ozge; Kucukguzel, Ilkay; Kucukguzel, S. GunizIn trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them,N '-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide(3k)showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 1.38 mu M on PC3 with SI = 432.30 and IC50 = 46.09 mu M on MCF-7 with SI = 12.94). Further investigation confirmed that3kdisplayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound3kwas identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound3kdeserves further development as a potential anticancer agent. [GRAPHICS] .Publication Open Access Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity(2022-11-01) BİNGÖL ÖZAKPINAR, ÖZLEM; KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; Bulbul B., Ding K., Zhan C., Ciftci G., YELEKÇİ K., Gurboga M., BİNGÖL ÖZAKPINAR Ö., Aydemir E., Baybag D., ŞAHİN F., et al.Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.Publication Metadata only Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2016) ÖZSAVCI, DERYA; Kulabas, Necla; Tatar, Esra; Ozakpinar, Ozlem Bingol; Ozsavci, Derya; Pannecouque, Christophe; De Clercq, Erik; Kucukguzel, IlkayIn this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18,19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 mu M (PC-3 cells), 7.90 mu M (A549/ATCC cells) and 7.71 mu M (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 mu M. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2. (C) 2016 Elsevier Masson SAS. All rights reserved.Publication Open Access Novel azole-urea hybrids as VEGFR-2 inhibitors: Synthesis, in vitro antiproliferative evaluation and in silico studies(2023-12-15) KULABAŞ, NECLA; DANIŞ, ÖZKAN; KÜÇÜKGÜZEL, İLKAY; Shirzad M. M., KULABAŞ N., Erdoğan Ö., Çevik Ö., Dere D., Yelekçi K., DANIŞ Ö., Küçükgüzel İ.The vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase known to be abnormally expressed in various malignant tumors, including breast cancer, and is considered one of the most important contributors to tumor angiogenesis. Sorafenib is one of many VEGFR-2 inhibitors that have received approval for clinical use from the US FDA in recent years. Accordingly, in this study, the synthesis of two new pyrazoles, six 1,3,4-oxadiazoles, four 1,3,4-thiadiazoles, and ten 1,2,4-triazole-3-thione derivatives having structural characteristics similar to sorafenib was carried out. A preliminary screening of synthesized compounds and known inhibitors sorafenib and staurosporine at 10 µM concentration on in vitro activity of VEGFR-2 was performed, and compounds 10c, 8a, and 11 g were identified as the most potent derivatives with% VEGFR-2 residual activities lower than 30%, and dose-dependent inhibition studies was carried out to determine the IC50 values of these inhibitors. Compound 10c was found to be the most potent inhibitor of VEGFR-2 activity with an IC50 value of 0.664 µM. The anti-proliferative activity of synthesized derivatives was assessed against a breast carcinoma (MCF-7) cell line, a triple negative human breast adenocarcinoma (MDA-MB-231) cell line, and noncancerous fibroblast cells (L929). Compound 8a displayed superior activity when compared to sorafenib against MCF-7 (7.69 fold) and MDA-MB-231 (1.52 fold) cell lines while displaying 3.75-fold less toxicity against the normal L929 cell line. Annexin V binding assay revealed that compound 8a significantly increased early and late apoptosis in MCF-7 cells and late apoptosis and necrosis in MDA-MB-231 cells. Computational studies such as molecular docking and ADMET evaluation were performed to elucidate the binding interactions and drug-likeness of the synthesized compounds. The results indicate that compound 8a could be a promising candidate for the development of a novel anti-angiogenic and anti-proliferative agent.Publication Metadata only One-pot, Four-Component Green Synthesis, Carbonic Anhydrase II Inhibition and Docking Studies of 5-Arylidenerhodanines(WILEY-V C H VERLAG GMBH, 2018) KULABAŞ, NECLA; Mermer, Arif; Demirbas, Neslihan; Colak, Ahmet; Demir, Elif Ayazoglu; Kulabas, Necla; Demirbas, AhmetIn the present study, a planning strategy for N-substituted-5-arylidenerhodanines was developed by the condensation between 3-morpholinopropan-1-amine, aldehyde, ethyl bromoacetate and carbon disulfide in the presence of trimethylamine in water via a one-pot, sequential four component reaction at room temperature and additionally microwave and ultrasound irradiated techniques. The synthesis of arylidenerhodanine derivatives was performed through the optimized one pot strategy starting from commercially available materials in high yields and purity without troublesome work-ups, after recrystallization from an appropriate solvent. Enzyme inhibition activity screening studies on CA II was also carried out. IC50 values of some of examined molecules could be determined and it was observed that they were nanomolar level except for 1r, and lower than that of reference molecule. The inhibition in the range of 8.6-99.4% was seen in the presence of newly synthesized molecules at their reachable maximum concentration in the reaction mixtures. Among the examined molecules, 5a and 5p with the two lowest IC50 values were found to be the most potent inhibitors. In silico studies showed that all of the rhodanine derivatives have higher affinity than reference ligand against binding site, while none of the compounds have demonstrated any interaction with Zn2+ as with the classical sulfonamides.Publication Metadata only Publication Metadata only Design, synthesis and molecular modeling studies on novel moxifloxacin derivatives as potential antibacterial and antituberculosis agents(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019) TÜRE, ASLI; Ture, Asli; Kulabas, Necla; Dingis, Serap Ipek; Birgul, Kaan; Bozdeveci, Arif; Karaoglu, Sengul Alpay; Krishna, Vagolu Siva; Sriram, Dharmarajan; Kucukguzel, IlkayTwenty-one novel alkyl/acyl/sulfonyl substituted fluoroquinolone derivatives were designed, synthesized and evaluated for their anti-tuberculosis and antibacterial activity. The targeted compounds were synthesized by the introduction of alkyl, acyl or sulfonyl moieties to the basic secondary amine moiety of moxifloxacin. Structures of the compounds were enlightened by FT-IR, H-1 NMR, C-13 NMR and HRMS data besides elemental analysis. Compounds were initially tested in vitro for their anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay. Minimal inhibitory concentration (MIC) values of all compounds were found between > 25.00-0.39 mu g/mL while compounds 1, 2 and 13 revealed an outstanding activity against M. tuberculosis H37Rv with MIC values of 0.39 mu g/mL. Activities of compounds 1-21 against to a number of Gram-positive and Gram-negative bacteria and fast growing mycobacterium strain were also investigated by agar well diffusion and microdilution methods. According to antimicrobial activity results, compound 13 was found the most potent derivative with a IC50 value of < 1.23 mu g/mL against Staphylococcus aureus and clinical strain of methicillin-resistant clinical strain of S. aureus.Publication Metadata only