Browsing by Author "Sujayev, Afsun"

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Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular Docking and Enzymatic Inhibition for Therapeutic Potential
(Humana Press inc, 2025) Farzaliyev, Vagif; Erturk, Adem; Huseynova, Afat; Demir, Yeliz; Kiziltas, Hatice; Sujayev, Afsun; Gulcin, Ilhami
In this study, a series of new oxirane and thiirane (2a-g), were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). So, in the first stage, 1-chloro-3-phenothiazylpropanol-2 (2), methyl, methoxy-substituted oxirane, thiirane (2a and 2b), methyl, 1,2-aminopropanethiols (2c-2f), trifluorinated aminethiol derivative (2g), have been synthesized. The structures of synthesized compound were confirmed by IR, NMR analysis. Enzyme inhibition studies demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.21 +/- 0.072-12.64 +/- 0.12, 5.93 +/- 0.028- 81.87 +/- 12.52 and 61.43 +/- 10.01-344.22 +/- 33.87 nM, respectively. Additionally, molecular docking studies were conducted to investigate further the binding interactions of the most potent inhibitors with enzyme active sites, revealing strong hydrogen bonding, pi-stacking, and halogen interactions. These findings indicate that the synthesized compounds exhibit high affinity and specificity for the target enzymes, suggesting their potential for further development as therapeutic agents. Future studies will focus on optimizing the structural features of these compounds to enhance their selectivity and bioavailability, conducting in vivo evaluations to assess their pharmacokinetic and pharmacodynamic properties, and exploring their potential applications in the treatment of neurodegenerative and metabolic disorders.
Synthesis and Biological Evaluation of Aminomethyl and Alkoxymethyl Derivatives as Carbonic Anhydrase, Acetylcholinesterase and Butyrylcholinesterase Inhibitors
(Taylor & Francis Ltd, 2017) Gulcin, Ilhami; Abbasova, Malahat; Taslimi, Parham; Huyut, Zubeyir; Safarova, Leyla; Sujayev, Afsun; Supuran, Claudiu T.
Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II). Both hCA isoenzymes were significantly inhibited by the recently synthesized molecules, with Ki values in the range of 58-157 nM for hCA I, and 81-215 nM for hCA II. Additionally, the Ki parameters of these molecules for BChE and AChE were calculated in the ranges 23-88 and 18-78 nM, respectively.
Synthesis and Investigation of the Conversion Reactions of Pyrimidine-Thiones With Nucleophilic Reagent and Evaluation of Their Acetylcholinesterase, Carbonic Anhydrase Inhibition, and Antioxidant Activities
(Wiley, 2018) Taslimi, Parham; Sujayev, Afsun; Turkan, Fikret; Garibov, Emin; Huyut, Zubeyir; Farzaliyev, Vagif; Gulcin, Ilhami
The conversion reactions of pyrimidine-thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2-epoxy propane, 1,2-epoxy butane, and 4-chlor-1-butanol and pyrimidine-thiones. These pyrimidine-thiones derivatives (A-K) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 +/- 33.7-467.5 +/- 126.9nM. The hCA I and II were effectively inhibited by these compounds, with K-i values in the range of 4.3 +/- 1.1-9.1 +/- 2.7nM for hCA I and 4.2 +/- 1.1-14.1 +/- 4.4nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed K-i value of 13.9 +/- 5.1nM against hCA I and 18.1 +/- 8.5nM against hCA II. The antioxidant activity of the pyrimidine-thiones derivatives (A-K) was investigated by using different in vitro antioxidant assays, including Cu(2+)and Fe(3+)reducing, 1,1-diphenyl-2-picrylhydrazyl (DPPH center dot) radical scavenging, and Fe(2+)chelating activities.
Synthesis of New Cyclic Thioureas and Evaluation of Their Metal-Chelating Activity, Acetylcholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibition Profiles
(Wiley, 2017) Taslimi, Parham; Sujayev, Afsun; Garibov, Emin; Nazarov, Nazar; Huyut, Zubeyir; Alwasel, Saleh H.; Gulcin, Ilhami
In the presence of trifluoracetic acid (TFAA), an efficient method for the synthesis of tetra(hexa)hydropyrimidinethione-carboxylates has been used on the basis of three-component condensation of thiourea with its different aldehydes and -diketones. Some novel cyclic thioureas were synthesized, and their hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors and metal-chelating properties were evaluated. K-i values of novel synthesized compounds for AChE and BChE are in the range of 51.84-135.96 and 143.96-274.55 nM, respectively. Also, HCA I and II were effectively inhibited by these novel compounds, with K-i values in the range of 404.16-745.13 nM for hCA I and of 434.20-689.57 nM for hCA II, respectively. Additionally, acetazolamide (AZA), clinically used as a CA inhibitor, with a K-i value of 883.68 +/- 121.27 nM in hCA I and 1008.66 +/- 144.70 nM in hCA II. Also, tacrine inhibited AChE and BChE showed K-i values of 314.63 +/- 31.66 and 373.57 +/- 75.07 nM, respectively.