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Öğe 2-Methyl-4-nitrophenoxy based thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole compounds as multitarget enzyme inhibitors: Synthesis, biological and computational studies(Elsevier, 2026) Alagoz, Tenzile; Yilmaz, Sunay; Ozden, Eda Mehtap; Alagoz, Mehmet Abdullah; Zengin, Mustafa; Bilgicli, Hayriye Genc; Gulcin, IlhamiNovel thiosemicarbazide (3a-d), 1,2,4-triazole (4a-d), and 1,3,4-thiadiazole (5a-d) derivatives were obtained in high total yields of 57-66%, 40-51%, and 40-53%, respectively, and they were evaluated for inhibitor activity against acetylcholinesterase, and human carbonic anhydrase isoforms I and II (hCAs I and II). They were demonstrated to have effective inhibition profiles with Ki values of 20.08+4.80-152.41+66.19 nM against hCA I, 64.57+20.74-356.58+176.92 nM against hCA II and 4.55+1.24-61.30+28.60 nM against AChE. On the other hand, acetazolamide showed Ki value of 30.69+9.31 nM against hCA I, and 40.08+6.38 nM against hCA II isoform. Additionally, Tacrine inhibited AChE and demonstrated Ki values of 3.51+1.56 nM. The affinities of the compounds towards hCA I, hCA II and AChE were evaluated by in silico studies. In molecular docking studies, 3c (-7.453 kcal/mol), 3d (-7.380), 5b (-7.372 kcal/mol) showed high affinity towards AChE. In MD simulation studies with the most active compound 3c, it was observed that the compound remained stable in the active site of AChE for 150 ns (Average RMSD < 3.0 & Aring;). The ADMET properties of the synthesized compounds were evaluated in silico. All compounds exhibited pharmacological properties and did not display adverse toxic effects. The inhibition of CA and AChE is a powerful pharmacological tool with diverse clinical applications. By targeting different CA and AChE, inhibitors can treat eye diseases, neurological disorders, metabolic conditions, Alzheimer's disease and even cancer, highlighting their broad therapeutic potential. MD simulations of the most active compound, 3c, confirmed its stability in the AChE active site for 150 ns (average RMSD < 3.0 & Aring;). Furthermore, in silico ADMET analysis showed that all compounds had favorable pharmacokinetic profiles without significant toxic effects. These results demonstrate that novel 1,3,4-thiadiazole derivatives have considerable potential as selective and potent multitarget enzyme inhibitors and are promising candidates for further pharmaceutical development.Öğe 2-Phenyl substituted Benzimidazole derivatives: Design, synthesis, and evaluation of their antiproliferative and antimicrobial activities(Springer Birkhauser, 2022) Ersan, Ronak Haj; Kuzu, Burak; Yetkin, Derya; Alagoz, Mehmet Abdullah; Dogen, Aylin; Burmaoglu, Serdar; Algul, OztekinThe inability to meet the desired outcomes of anticancer treatment and decrease in treatment success of bacterial and fungal infections accelerated research in these areas. Our research group has conducted numerous studies, especially on benzimidazole ring systems' antiproliferative and antimicrobial activities. In this study, the antiproliferative activity of benzimidazole compounds was tested against A549, A498, HeLa, A375, and HepG2 cancer cell lines by MTT assay. All compounds exhibited good to potent antiproliferative activity against all tested cancer cell lines. Compounds 6-chloro-2-(4-fluorobenzyl)-1H-benzo[d] imidazole (30) and 6-chloro-2-phenethyl-1H-benzo[d]imidazole (46) were especially active against HeLa and A375 cancer cell lines with IC50 values in the range of 0.02-0.04 mu M. In contrast, compounds 6-chloro-2-((p-tolyloxy)methyl)-1H-benzo[d] imidazole (67) and 5(6)-chloro-2-((4-hydroxyphenoxy)methyl)-1H-benzimidazole (68) were active against A549 and A498 cancer cell lines with an IC50 value of 0.08 mu M. These compounds (30, 46, 67, and 68) were less toxic to normal human cells than the positive control compound methotrexate, which was screened to determine its toxicity against normal cell lines (HEK293). In the second part of the study, all compounds were tested to demonstrate their antimicrobial properties. All compounds exhibited moderate activity against all tested bacteria and fungi. However, some phenoxy methyl derivatives 5-chloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d]imidazole (69) and 5,6-dichloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d] imidazole and (74) were most active against Candida (<3.90 mu g/mL). Molecular docking studies were carried out against certain proteins in order to identify potential targets of the antiproliferative effects of the synthesized compounds. The docking scores of the compounds were found to be significantly compatible with the antiproliferative activity results. [GRAPHICS] .Öğe Antioxidant and antithrombotic properties of fruit, leaf, and seed extracts of the Halhal? olive (Olea europaea L.) native to the Hatay region in Turkey(Kemerovo State Univ, 2023) Batcioglu, Kadir; Kucukbay, Fatumetuzzehra; Alagoz, Mehmet Abdullah; Gunal, Selami; Yilmaztekin, YakupThe olive (Olea europaea L.) is one of the most important plants grown in many Mediterranean countries that has a high economic value. Olives, which are specific to each region, have different bioactive components. In this study, we investigated the phenolic/flavonoid contents, as well as antioxidant, antimicrobial, and antithrombotic activities of the fruit, leaf, and seed extracts obtained from the Halhali olive grown in Arsuz district of Hatay, Turkey. Antioxidant activities of the phenolic compounds found in the olive fruit, seed, and leaf extracts were determined by employing established in vitro systems. Total phenolics were determined as gallic acid equivalents, while total flavonoids were determined as quercetin equivalents. Also, we evaluated a possible interaction between oleuropein and aggregation-related glycoproteins of the platelet surface via docking studies. The extracts showed effective antioxidant activity. The seed extract had the highest phenolic content of 317.24 mu g GAE, while the fruit extract had the highest flavonoid content of 4.43 mu g. The highest potential for metal chelating activity was found in the leaf extract, with an IC50 value of 13.33 mg/mL. Also, the leaf extract showed higher levels of antioxidant, antithrombotic, and antimicrobial activity, compared to the fruit and seed extracts. The docking scores of oleuropein against the target molecules GPVI, alpha 2 beta 1, and GPIb alpha were calculated as -3.798, -4.315, and -6.464 kcal/mol, respectively. The olive fruit, leaf, and seed extracts used as experimental material in our study have remarkable antioxidant, antimicrobial, and antithrombotic potential.Öğe Assessing the Antiangiogenic Effects of Chalcones and Their Derivatives(Taylor & Francis Ltd, 2024) Burmaoglu, Serdar; Gobek, Arzu; Anil, Derya Aktas; Alagoz, Mehmet Abdullah; Guner, Adem; Guler, Cem; Hepokur, CeylanPathological angiogenesis plays a critical role in tumorigenesis and tumor progression, and anti-angiogenesis therapies have evinced promising antitumor effects in solid tumors. Chalcone skeleton has been regarded as a potential antitumor agent that also targets angiogenesis. In this study, we designed twenty-one non-fluoro-substituted chalcones (13-18, 24-27) and saturated chalcone derivatives (19-23, 28-33) as anti-angiogenic compounds. During the initial stage, these compounds were assessed for their anti-cancer activities against MCF-7 cancer cell lines according to the MTT assay. The compounds revealed satisfactory anti-proliferative capability. An ex vivo fertilized hens' egg-chorioallantoic membrane (HET-CAM) angiogenic study was conducted for the compounds to gauge their mortality and toxicity, which, in turn, revealed a potent anti-angiogenic effect. Eight compounds (16, 17, 21, 24, 26, 27, 29, and 31) significantly reduced densities of capillaries on CAM, whereas compounds 27 and 29 were the most effective anti-angiogenic agents, when compared with Suramin. Moreover, RT-qPCR analysis demonstrated that the anti-angiogenic activity was associated with the fold changes of VEGFR2. Molecular docking studies were conducted for compounds to investigate their mode of interaction within the binding site of VEGFR-2 kinases. This work provided a basis for further design, structural modification, and development of chalcone derivatives as new anti-angiogenic agents.Öğe Bacterial Cellulose Production in Dried Apricot Extract Medium: Experimental/Theoretical Characterization and Application in Yeast Immobilization for Dye Removal(Amer Chemical Soc, 2025) Boran, Filiz; Koytepe, Suleyman; Aslan, Gizem; Birhanli, Emre; Yesilada, Ozfer; Alagoz, Mehmet AbdullahBacterial cellulose (BC) was produced in dried apricot extract medium (DAEM) by Gluconacetobacter xylinus B759. The BC yield obtained from DAEM containing 0.5 g of glucose after 10 days of incubation at 30 degrees C was determined as 9.67 g/L. BC was used as an immobilization matrix for Saccharomyces cerevisiae. First, structural characterizations of BC and BC-yeast were carried out. Also, their surface and morphological properties were examined by SEM and atomic force microscopy. Yeast attachment and growth kinetics were also evaluated experimentally and theoretically. This yeast-immobilized BC (BC-yeast) membrane was used for removal of textile dye, Reactive Blue 171 (RB 171). The results showed that yeast was successfully immobilized on BC and could be effectively used for dye removal. When 12 lyophilized BC-yeast samples were used, 52% and 21% dye removal values were obtained under static and shaking (150 rpm) conditions, respectively. These values were 49% and 50% for wet BC-yeast samples after 24 h, respectively. Additionally, density functional theory calculations were performed to elucidate the interactions responsible for the adsorption of RB 171 dye onto the BC structure, and it was shown that the RB 171 structure is energetically very strong and favorably bound to the BC surface. It was found that BC-yeast was highly effective for RB 171 removal. Therefore, the BC produced in DAEM could be used as an immobilization matrix and as a low-cost, effective, and alternative adsorbent for the removal of dyes from dye-containing wastewaters.Öğe Benzoxazole Derivatives as Dual p38α Mitogen-Activated Protein Kinase and Acetylcholinesterase Inhibitors: Design, Synthesis, and Evaluation for Alzheimer's Disease and Cancer Therapy(Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, Gizem; Alagoz, Mehmet Abdullah; Hepokur, Ceylan; Dilek, Esra; Algul, OztekinAlzheimer's disease (AD), the most prevalent form of dementia, leads to progressive cognitive decline due to pathological hallmarks including amyloid plaques, neurofibrillary tangles, synaptic loss, neuroinflammation, and neuronal cell death, highlighting the urgent need for multitarget therapeutic strategies. The p38 alpha mitogen-activated protein kinase (p38 alpha MAPK) pathway is a key regulator of neuroinflammation and has been implicated in AD pathogenesis. Additionally, dysregulation of p38 alpha MAPK is associated with tumorigenesis, making it a promising target for both neurodegenerative and proliferative diseases. In this article, a series of benzoxazole derivatives is designed and synthesized to evaluate their dual inhibitory potential against p38 alpha MAPK and acetylcholinesterase (AChE), aiming for a multifaceted therapeutic approach to AD. A total of 31 compounds are synthesized and assessed for their antiproliferative activity, p38 alpha MAPK inhibition, and AChE inhibitory effects. In vitro assays demonstrate that several compounds exhibit potent dual inhibition of p38 alpha MAPK and AChE, while molecular docking studies provide insights into their binding interactions within the active sites. These findings suggest that benzoxazole-based scaffolds offer a promising framework for the development of dual-acting inhibitors targeting both neuroinflammation and tumorigenesis. Further in vivo and mechanistic studies are warranted to explore their therapeutic potential.Öğe Bisbenzoxazole Derivatives: Design, Synthesis, in Vitro Antimicrobial, Antiproliferative Activity, and Molecular Docking Studies(Taylor & Francis Ltd, 2022) Ersan, Ronak Haj; Alagoz, Mehmet Abdullah; Dogen, Aylin; Duran, Nizami; Burmaoglu, Serdar; Algul, OztekinFour series of bisbenzoxazole derivatives were designed, synthesized, and screened for antiproliferative and antimicrobial activities. Generally, all synthesized bisbenzoxazoles (9-24) displayed significant antiproliferative activity; these effects were shown to be related to oxazole rings and substituents in bisbenzoxazole compounds. Especially, the series bearing chloro-substituent (9-12) exhibited better antiproliferative activity with higher selectivity than the other series (13-24); the IC50 values were observed in the range of 0.045-0.342 mu M. Interestingly, only the compound with a nitro substituent (22) showed maximum potency with an IC50 value of 0.011 mu M, which is two-fold more active than the standard drug methotrexate, with moderate selectivity. The compounds bearing fluoro-substituent (14-16) were found to exhibit potent antibacterial activity against the Gram-positive Enterococcus faecalis, with a MIC value of 62.5 mu g/mL, and moderate activity against Gram-negative bacteria and fungi. Only the compound 23 showed potent activity against Escherichia coli, with a MIC value of 62.5 mu g/mL. In order to better evaluate the activity results, crystal structures of five different proteins Human Anaplastic Lymphoma Kinase (PDB ID: 2XP2), CYP2C8dH complexed (PDB ID: 2NNI), factor-human kinase-beta enzyme IKK-beta enzyme (PDB ID: 4KIK), a tubulin heterodimer complex containing alpha and beta sub-units (PDB ID: 1Z2B) and penicillin-binding protein 4 (PBP4) from Enterococcus faecalis (PDB ID: 6MKI) were used in the docking study to examine antiproliferative and antimicrobial activity. Finally, an ADMET screening test was applied to determine the drug-like, toxicological, and optimum physicochemical properties for all of the synthesized compounds. The strategy applied in this research may act as a perspective for the rational design of potential anticancer drugs.Öğe CARDIOPROTECTIVE AND ANTIOXI DAN ACTIVITY OF BLUEBERRY ANTHOCYANINE AND POLYPHENOLS IN RATS(Elsevier Science Bv, 2009) Karakurt, Cemsit; Gursoy, Sule; Alagoz, Mehmet Abdullah; Karakurt, Arzu; Aktays, Goknur; Kocak, Gulendam[Abstract Not Available]Öğe Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis, molecular docking and anticonvulsant studies(Taylor & Francis Ltd, 2016) Karatas, Mert Olgun; Uslu, Harun; Sari, Suat; Alagoz, Mehmet Abdullah; Karakurt, Arzu; Alici, Bulent; Bilen, CigdemAmong many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties. In this study, we prepared fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives and evaluated their hCA inhibitory activities and along with fourteen previously synthesized derivatives we scanned their anticonvulsant effects. As all compounds inhibited purified hCA isoforms I and II, some of them also proved protective against Maximal electroshock seizure (MES) and ScMet induced seizures in mice. Molecular docking studies with selected coumarin derivatives have revealed that these compounds bind to the active pocket of the enzyme in a similar fashion to that previously described for coumarin derivatives.Öğe Deep learning approach to the discovery of novel bisbenzazole derivatives for antimicrobial effect(Elsevier, 2024) Barcin, Tunga; Yucel, Mehmet Ali; Ersan, Ronak Haj; Alagoz, Mehmet Abdullah; Dogen, Aylin; Burmaoglu, Serdar; Algul, OztekinBecause of the growing bacterial resistance to antibiotics, the discovery of new antibiotics is critical. The search for new antimicrobial drugs that are effective in treating new and existing microbial diseases is arduous and timeconsuming. Deep learning (DL) can help find potential candidates resulting in a more efficient, and cost-effective, and it is more useful on large datasets than other algorithms.Our research team focused on developing an effective DL workflow for discovering new antimicrobial agents. Our group has previously synthesized and tested bisbenzazole structures with various linkers for a variety of pharmacological activities. Antimicrobial activities of bisbenzazole compounds have been also reported in the literature. Deep Neural Networks (DNN) were used to predict the activity of all bisbenzazole compounds synthesized by our group against Staphylococcus aureus and Candida albicans. DNN successfully predicted compounds 16, 17, and 30 out of six molecules (11, 16, 17, 29, 30, and 33) with activity results of 31.25 mu g /mL or better results based on in vitro studies. Compounds 13 and 15 out of four molecules (13, 15, 29, and 30) for C. albicans were successfully predicted. Molecular modeling studies were also carried out, and the compounds' docking scores agreed with the DNN models and in vitro antimicrobial activity results. Finally, this workflow, which includes deep learning, molecular docking, and in vitro studies, is a dependable and efficient way of discovering new antimicrobial agents for S. aureus and C. albicans.Öğe Design and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance(Elsevier, 2025) Oksuz, Zehra; Aktekin, Mine Buga; Alagoz, Mehmet Abdullah; Kuzucu, Mehmet; Serin, Mehmet Sami; Algul, OztekinHCV NS3/4A protease is a crucial target for antiviral therapy, but resistance remains a significant challenge. Understanding substrate recognition is key to developing effective inhibitors. The aim of this study was to investigate four new compounds (10-12 and 13) that mimic natural substrate binding. Compound activities were determined with enzymatic assays and anti-proliferative activities were evaluated. Compound 12 exhibited the highest potency with an IC50 of 17.78 mu M and a Ki value of 16.39 mu M. All compounds demonstrated moderate to high anti-proliferative activity against HFF-1 and HepG2 cells, with 12 and 11 showing the most potent effects. In silico studies revealed that compounds 11 and 12 formed stable complexes with the HCV NS3/4A protease, establishing significant interactions with key residues of the catalytic triad. Their docking scores and molecular dynamics simulations were comparable to those of the reference molecule, simeprevir. These findings suggest that compounds 10-12 and 13 hold promise as potential therapeutic agents against HCV, warranting further investigation.Öğe Design, Synthesis, and Biological Evaluation of Some Benzothiazolone Derivatives as Cholinesterase Inhibitors(Wiley-V C H Verlag Gmbh, 2022) Alagoz, Mehmet Abdullah; Akkaya, Didem; Arslan, Gulnur; Uludag, Berk; Ozdemir, Zeynep; Barut, Burak; Onkol, TijenIn this study, nine new benzothiazolone derivatives (6 a-i) were designed and synthesized to identify potent cholinesterase inhibitors. The compounds were tested in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and found to be selective to BChE. Compound 6 f proved the most potent derivative (IC50=12.25 +/- 0.23 mu M) against BChE and was identified as a mixed-type inhibitor with a K-i value of 4.45 +/- 0.35 mu M according to the kinetic studies. Molecular modelling suggested that the derivatives were druglike and non-PAINS. Compound 6 f showed good fit in BChE active site interacting with the key sites important for enzyme activity according to the molecular docking study.Öğe Design, Synthesis, and In Silico Analyses of Nitroimidazole Derivatives Targeting Cholinesterases(Wiley-V C H Verlag Gmbh, 2025) Biyik, Busra; Tarikogullari, Ayse H.; Alagoz, Mehmet Abdullah; Demir, Yeliz; Gulcin, Ilhami; Burmaoglu, Serdar; Algul, OztekinThe increasing incidence of diseases and the constraints of current treatments require expedited drug development. Drug repositioning presents an effective approach for discovering new therapeutic applications for drugs already in clinical use. This study examines the efficacy of metronidazole and secnidazole, which are presently utilized as antiprotozoal agents, in the treatment of Alzheimer's disease via ester modifications. The secondary alcohol group in nitroimidazole structures underwent esterification with acetyl, pivaloyl, cyclopropyl, and cyclohexyl carbonyl chlorides. The compounds exhibited significant inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with Ki values between 52.40 +/- 6.99 nM and 240.80 +/- 45.56 nM for AChE and 77.82 +/- 18.01 nM and 323.70 +/- 56.21 nM for BChE. Molecular docking studies demonstrated significant interactions of the most active compounds (MNZ 8 and MNZ 4) with essential residues, including Trp84 and Phe330 in AChE, as well as Trp82 and active-site water molecules in BChE. These findings corroborate their inhibitory potential, notwithstanding initial positional alterations observed during simulations. The synthesized compounds' absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties were also assessed in silico. All compounds demonstrated drug-like properties and did not exhibit undesirable toxic effects. The findings indicate that repositioned derivatives of metronidazole and secnidazole may serve as promising lead compounds for the development of cholinesterase inhibitors aimed at treating Alzheimer's disease.Öğe Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors(Mdpi, 2022) Alagoz, Mehmet Abdullah; Oh, Jong Min; Zenni, Yaren Nur; Ozdemir, Zeynep; Abdelgawad, Mohamed A.; Naguib, Ibrahim A.; Ghoneim, Mohammed M.Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 mu M, followed by TR2 (IC50 = 0.27 mu M). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K-i values of 0.230 +/- 0.004 and 0.149 +/- 0.016 mu M, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.Öğe Development of Benzoxazole Derivatives Targeting mTOR: A Promising Approach for Breast Cancer Therapy(Wiley-V C H Verlag Gmbh, 2025) Alagoz, Mehmet Abdullah; Resitoglu, Meryem Temiz; Kuzu, Burak; Sabrie, Zainab; Yetkin, Derya; Zobi, Cengiz; Tiftik, Rukiye NalanClinical use of mTOR inhibitors in cancer treatment is well established due to the critical role of mTOR signaling in tumor progression. In this study, we report the structure-based design and biological evaluation of a series of benzoxazole derivatives as potential mTOR inhibitors. Cytotoxicity studies using MTT assays showed that compounds B4, B11, B12, and B20 exhibited significant antiproliferative effects against breast cancer cell lines with IC50 values between 4.96 and 9.82 mu M. Colorimetric enzymatic assays further revealed that among these, only B12 and B20 effectively inhibited mTOR phosphorylation at Ser2448 in MCF-7 cells. Additionally, both compounds modulated the expression of key apoptotic proteins, including Bax, caspase-3, p53, and Bcl2. Molecular docking studies against the 4JT5 protein demonstrated binding affinities with docking scores ranging from -7.084 to -7.426 kcal/mol, comparable to the reference compound P2X (-7.309 kcal/mol). Molecular dynamics simulations over 150 ns confirmed the stability of B12 and B20 in the active site, with an average RMSD of 2.8 & Aring; and 3.0 & Aring;, respectively. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the synthesized compounds were evaluated in silico. Among them, B4, B11, B12, and B20 exhibited drug-like characteristics and showed no undesirable toxic effects. These findings highlight the potential of B12 and B20 as lead compounds for the development of novel mTOR inhibitors in breast cancer therapy.Öğe An efficient synthesis of novel di-heterocyclic benzazole derivatives and evaluation of their antiproliferative activities(Taylor & Francis Inc, 2021) Algul, Oztekin; Ersan, Ronak Haj; Alagoz, Mehmet Abdullah; Duran, Nizami; Burmaoglu, SerdarA series of unsymmetrical nine di-heterocyclic compounds of benzazole derivatives were synthesized at one step via cyclization reaction. The compounds evaluated forin vitrocytotoxic activity against A549, A498, HeLa, and HepG2 cancer cell lines. The biological evaluation results show that23, 26and29exhibit better activity against HepG2 and HeLa cancer cell lines. Compound23also showed good activity against A549, and A498 cancer cell lines. The analogs were further performed molecular docking studies against human cytochrome P450 2C8 monooxygenase enzyme, calculated some theoretical quantum parameters, ADMET descriptor and molecular electrostatic potential analysis. The strategy applied in this research work may act as a perspective for the rational design of potential anticancer drugs. Communicated by Ramaswamy H. SarmaÖğe Electrochemical and in Silico Investigations of the Interaction between Nitro Blue Tetrazolium Chloride and Bovine Serum Albumin(Eurasia Acad Publ Group (Eapg), 2022) Kazici, Dilek; Alagoz, Mehmet Abdullah; Savan, Ebru KuyumcuThe binding ability of the drug on its interaction with the protein will also significantly affect the apparent volume of distribution of the drugs and, in many cases the rate of elimination of the drugs. The interactions of proteins and other molecules are a fascinating topic applied to surface technologies and sensors. Therefore, it is aimed to determine the NBTCand to elucidate its interaction with Bovine Serum Albumin (BSA) by electrochemical and in silico studies in this paper. The reduction in BSA oxidation signals measured by differential pulse voltammetry upon incubation with different NBTC concentrations indicated that NBTC was bound to BSA. In addition, in silico (molecular modeling and molecular dynamics) studies have been conducted on the interactions of NBTC with proteins in plasma. As a result of the in silico studies investigated the interactions of NBTC with serum albumin, its binding affinity, and the dynamic process in the binding state. In silico studies showed that NBTC binds to BSA with high affinity (with-7.986 kcal/mol docking score), and this binding was stable (with a 3.0 average RMSD value). Eventually, the results of the electrochemical and modeling studies were perfectly matched.Öğe Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis(Springer, 2021) Ersan, Ronak Haj; Alagoz, Mehmet Abdullah; Ertan-Bolelli, Tugba; Duran, Nizami; Burmaoglu, Serdar; Algul, OztekinIn the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure-activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound31is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate. [GRAPHICS]Öğe Histological assessment of liver and stomach damage caused by pyridazinone derivative antidepressant agents(Taylor & Francis Ltd, 2022) Ozdemir, Zeynep; Karakurt, Arzu; Taslidere, Elif; Vardi, Nigar; Alagoz, Mehmet Abdullah; Parlakpinar, Hakan; Uslu, HarunDepression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.Öğe Inhibition of Cholinesterases by Benzothiazolone Derivatives(Mdpi, 2022) Alagoz, Mehmet Abdullah; Kim, Seong-Min; Oh, Jong Min; Arslan, Gulnur; Ozdemir, Zeynep; Sari, Suat; Ozcelik, Azime BernaThirteen benzothiazolone derivatives (M1-M13) were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs) and monoamine oxidases (MAOs). All the compounds inhibited ChEs more effectively than MAOs. In addition, most of the compounds showed higher inhibitory activities against butyrylcholinesterase (BChE) than acetylcholinesterase (AChE). Compound M13 most potently inhibited BChE with an IC50 value of 1.21 mu M, followed by M2 (IC50 = 1.38 mu M). Compound M2 had a higher selectivity index (SI) value for BChE over AChE (28.99) than M13 (4.16). The 6-methoxy indole group of M13 was expected to have a greater effect on BChE inhibitory activity than the other groups. Kinetics and reversibility tests showed that M13 was a reversible noncompetitive BChE inhibitor with a K-i value of 1.14 +/- 0.21 mu M. In a docking simulation, M13 is predicted to form a hydrogen bond with the backbone carbonyl group of Ser287 of BChE through its methoxy indole moiety and pi-pi interactions between its benzothiazolone group and the side chain of Trp82 with the five-membered pyrrole ring and with the six-membered benzene ring. From these results, it is suggested that M13 is a BChE inhibitor and a potential candidate agent for the treatment of Alzheimer's disease.
