Yazar "Adem, Sevki" seçeneğine göre listele

Listeleniyor 1 - 4 / 4
  • [ X ]
    Öğe
    Activation and inhibition effects of some natural products on human cytosolic CAI and CAII
    (Springer Birkhauser, 2019) Adem, Sevki; Akkemik, Ebru; Aksit, Huseyin; Guller, Pinar; Tufekci, Ali Riza; Demirtas, Ibrahim; Ciftci, Mehmet
    Carbonic anhydrases (CAs) play a significant function in diverse pathological and physiological processes. Their inhibitors and activators are suitable molecules to use as a drug in the treatment of different disease. In the present study, seven natural compounds, namely didymin, retusin isoquercitrin, silymarin, verbascoside, teucroside, and 3'-O-methylhypolaetin 7-O-[6'-O-acetyl-beta-D-allopyranosyl-(1 -> 2)]-6 ''-O-acetyl-beta-D-glucopyranoside were isolated from Mentha spicata, Sideritis libanotica linearis, Platanus orientalis, Teucrium chamaedrys subsp. chamaedrys, and Silybum marianum. The influences of compounds on the carbonic anhydrase I(hCAI) and II(hCAII) purified from human erythrocytes were tested. Five phenolic compounds acted as an inhibitor on the activity of hCAI, and IC50 values were computed between 18.16 and 172.5 mu M. Isozyme hCAII is only inhibited by silymarin with an IC50 value of 43.12 mu M. This isoenzyme was effectively activated by five natural compounds with AC(50) values in the range of 2.98-18.53 mu M. To understand the binding patterns of molecules that show activation effect against hCAII, molecular docking was done using Leadit 2.3.2 software, and calculated between -19.05 and -14.42 (kJ/mol) binding energies. Both in vitro and in silico results demonstrated that the best activators against hCAII were teucroside and isoquercitrin, with AC(50) values of 2.98 and 3.17 mu M, and binding energies -19.05 and -18.01 (kJ/mol), respectively. According to the ADME results, retusin demonstrated physicochemical and pharmacokinetic properties specific to the drug candidates.
  • [ X ]
    Öğe
    Inhibition Effects of Some Non-Proteinogenic Amino Acid Derivatives on Carbonic Anhydrase Isoenzymes and Acetylcholinesterase: An In Vitro Inhibition and Molecular Modeling Studies
    (Wiley-V C H Verlag Gmbh, 2024) Alim, Zuhal; Rawat, Ravi; Adem, Sevki; Eyuepoglu, Volkan; Akkemik, Ebru
    Amino acid derivatives are molecules of interest for medicinal chemistry and drug design studies due to their important chemical properties. In this study, the inhibition effects of some non-proteinogenic amino acid derivatives (hippuric acid (A), N-(9-Fluorenylmethoxycarbonyl)-D-valine (B), N-Z-(1-Benzotriazolylcarbonyl) methylamine (C), (S)-N-Z-1-Benzotriazolylcarbonyl-2-phenylethylamine (D)) on carbonic anhydrase I (hCA-I), II (hCA-II) isoenzymes and acetylcholinesterase (AChE) activity, whose inhibitors are of vital pharmacological importance, were examined. While carbonic anhydrase (CA) inhibitors are effective molecule candidates for the treatment of many diseases from glaucoma to cancer, acetylcholinesterase inhibitors are target molecules for the treatment of Alzheimer ' s disease. According to the results of this study, compound D had a strong inhibitory effect on hCA-I (IC50: 0.836 mu M) and hCA-II (IC50: 0.661 mu M), while compound B (IC50: 100 mu M) showed a strong inhibitory effect on AChE activity. In addition, inhibition results were supported by molecular modeling studies. We hope that the obtained results will contribute to the synthesis of new and effective amino acid derivative inhibitors for CA and AChE.
  • [ X ]
    Öğe
    Investigation of in vitro and in silico effects of some novel carbazole Schiff bases on human carbonic anhydrase isoforms I and II
    (Taylor & Francis Inc, 2022) Camadan, Yasemin; Cicek, Baki; Adem, Sevki; Calisir, Umit; Akkemik, Ebru
    Carbonic anhydrases (CAs, EC4.2.1.1) are metalloenzymes that catalyse reversible hydration reaction of carbon dioxide to bicarbonate and protons. In recent years, there has been a great interest in inhibitors/activators of carbonic anhydrase isoenzymes. Therefore, we investigated the effects of four different carbazole Schiff base derivatives, which are believed to have a potential to be used as a drug, on human carbonic anhydrase (hCA) isoenzymes I and II under in vitro conditions. The IC50 values of carbazole Schiff base derivatives were found to be in the range of 32.09-151.2 mu M for hCA isoenzyme I and 21.82-40.54 mu M for hCA isoenzyme II. Among all compounds, (E)-3-(((9-Octyl-9H-carbazole-3-yl)imino)methyl)benzene-1,2-diol (C3) had the strongest inhibitory effect on hCA isoenzyme II. It was determined that 2,3,4-trimethoxy and 4-hydroxy phenyl containing carbazole compounds have selective inhibition against hCA II isoenzyme. Docking studies were performed against hCA I and II receptors using induced-fit docking method. The compounds had affinity scores varying from -7.74 +/- 0.27 to -6.27 +/- 0.07 kcal/mol for hCA I and from -8.04 +/- 0.17 to -7.27 +/- 0.18 kcal/mol for hCA II. Communicated by Ramaswamy H. Sarma
  • [ X ]
    Öğe
    Synthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties
    (Taylor & Francis Inc, 2023) Calisir, Umit; Camadan, Yasemin; Cicek, Baki; Akkemik, Ebru; Eyupoglu, Volkan; Adem, Sevki
    The main objective of the present study was to synthesize potential inhibitor/activators of AChE and hCA I-II enzymes, which are thought to be directly related to Alzheimer's disease. Dithiodibenzothioate compounds were synthesized by thioesterification. Six different thiolate compounds produced were characterized by H-1-, C-13-NMR, FT-IR, LC-MS/MS methods. HOMO-LUMO calculations and electronic properties of all synthesized compounds were comprehensively illuminated with a semi-empirical molecular orbital (SEMO) package for organic and inorganic systems using Austin Model 1 (AM1)-Hamiltonian as implemented in the VAMP module of Materials Studio. In addition, the inhibition effects of these compounds for AChE and hCA I-II in vitro conditions were investigated. It was revealed that TE-1, TE-2, TE-3, TE-4, TE-5, and TE-6 compounds inhibited the AChE under in vitro conditions. TE-1 compound activated the enzyme hCA I while TE-2, TE-3 TE-4 compounds inhibited it. TE-5 and TE-6, on the other hand, did not exhibit a regular inhibition profile. Similarly, TE-1 activated the hCA II enzyme whereas TE-2, TE-3, TE-4, and TE-5 compounds inhibited it. TE-6 compound did not have a consistent inhibition profile for hCA II. Docking studies were performed with the compounds against AChE and hCA I-II receptors using induced-fit docking method. Molecular Dynamics (MD) simulations for best effective three protein-ligand couple were conducted to explore the binding affinity of the considered compounds in semi-real in-silico conditions. Along with the MD results, TE-1-based protein complexes were found more stable than TE-5. Based on these studies, TE-1 compound could be considered as a potential drug candidate for AD. Communicated by Ramaswamy H. Sarma