Publications by authors named "İlhami Gulçin"

263 Publications

Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors.

J Biomol Struct Dyn 2021 May 5:1-13. Epub 2021 May 5.

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

The underlying cause of many metabolic diseases is abnormal changes in enzyme activity in metabolism. Inhibition of metabolic enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and α-glucosidase (α-GLY) is one of the accepted approaches in the treatment of Alzheimer's disease (AD) and diabetes mellitus (DM). Here we reported an investigation of a new series of novel ureido-substituted derivatives with sulfamethazine backbone () for the inhibition of AChE, BChE, and α-GLY. All the derivatives demonstrated activity in nanomolar levels as AChE, BChE, and α-GLY inhibitors with values in the range of 56.07-204.95 nM, 38.05-147.04 nM, and 12.80-79.22 nM, respectively. Among the many strong -(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives () detected against ChEs, compound , the 4-fluorophenylureido derivative, demonstrated the most potent inhibition profile towards AChE and BChE. A comprehensive ligand/receptor interaction prediction was performed for the three metabolic enzymes providing molecular docking investigation using Glide XP, MM-GBSA, and ADME-Tox modules. The present research reinforces the rationale behind utilizing inhibitors with sulfamethazine backbone as innovative anticholinergic and antidiabetic agents with a new mechanism of action, submitting propositions for the rational design and synthesis of novel strong inhibitors targeting ChEs and α-GLY.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1916599DOI Listing
May 2021

LC-HRMS Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kınkor ().

Molecules 2021 Apr 23;26(9). Epub 2021 Apr 23.

Department of Chemistry, Faculty of Science, Ataturk University, 25240 Erzurum, Turkey.

Kınkor () is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kınkor (), some putative antioxidant methods such as DPPH· scavenging activity, ABTS scavenging activity, ferric ions (Fe) reduction method, cupric ions (Cu) reducing capacity, and ferrous ions (Fe)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and α-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kınkor () were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kınkor () demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kınkor () demonstrated IC values of 1.772 μg/mL against acetylcholinesterase (AChE), 33.56 ± 2.96 μg/mL against α-glycosidase, and 0.639 μg/mL against α-amylase enzyme respectively.
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http://dx.doi.org/10.3390/molecules26092469DOI Listing
April 2021

Synthesis, Characterization, and Inhibition Study of Novel Substituted Phenylureido Sulfaguanidine Derivatives as α-Glycosidase and Cholinesterase Inhibitors.

Chem Biodivers 2021 Apr 9;18(4):e2000958. Epub 2021 Mar 9.

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, 26470, Turkey.

A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2f) showed AChE and BChE inhibitory effects, with K values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide (2e) showed strong α-GLY inhibitory effect, with K values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD.
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http://dx.doi.org/10.1002/cbdv.202000958DOI Listing
April 2021

Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives.

Arch Pharm (Weinheim) 2021 May 4;354(5):e2000455. Epub 2021 Feb 4.

Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey.

3-Amino-2-ethylquinazolin-4(3H)-one (3) was synthesized in two steps from the reaction of amide (2), which was obtained from the treatment of methyl anthranilate (1) with propionyl chloride, with hydrazine. From the reaction of 3-amino-2-ethylquinazolin-4(3H)-one (3) with various aromatic aldehydes, novel benzylidenaminoquinazolin-4(3H)-one (3a-n) derivatives were synthesized. The structures of the novel molecules were characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy ( H-NMR and C-NMR), and high-resolution mass spectroscopy. The novel compounds were tested against some metabolic enzymes, including α-glucosidase (α-Glu), acetylcholinesterase (AChE), and human carbonic anhydrases I and II (hCA I and II). The novel compounds showed K values in the range of 244-988 nM for hCA I, 194-900 nM for hCA II, 30-156 nM for AChE, and 215-625 nM for α-Glu. The binding affinities of the most active compounds were calculated as -7.636, -6.972, -10.080, and -8.486 kcal/mol for hCA I, hCA II, AChE, and α-Glu enzymes, respectively. The aromatic ring of the quinazoline moiety plays a critical role in the inhibition of the enzymes.
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http://dx.doi.org/10.1002/ardp.202000455DOI Listing
May 2021

Synthesis and pharmacological effects of novel benzenesulfonamides carrying benzamide moiety as carbonic anhydrase and acetylcholinesterase inhibitors.

Turk J Chem 2020 16;44(6):1601-1609. Epub 2020 Dec 16.

Department of Chemistry, Faculty of Science, Atatürk University, Erzurum Turkey.

-(1-(4-Methoxyphenyl)-3-oxo-3-((4-( -(substituted)sulfamoyl)phenyl)amino)prop-1-en-1-yl)benzamides were designed since sulfonamide and benzamide pharmacophores draw great attention in novel drug design due to their wide range of bioactivities including acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and hCA II) inhibitory potencies. Structure elucidation of the compounds was carried out by 1H NMR, 13C NMR, and HRMS spectra. In vitro enzyme assays showed that the compounds had significant inhibitory potential against hCA I, hCA II, and AChE enzymes at nanomolar levels. Ki values were in the range of 4.07 ± 0.38 - 29.70 ± 3.18 nM for hCA I and 10.68 ± 0.98 - 37.16 ± 7.55 nM for hCA II while Ki values for AChE were in the range of 8.91 ± 1.65 - 34.02 ± 5.90 nM. The most potent inhibitors (Ki = 4.07 ± 0.38 nM, hCA I), (Ki = 10.68 ± 0.98 nM, hCA II , and (Ki = 8.91 ± 1.65 nM, AChE) can be considered as lead compounds of this study with their promising bioactivity results. Secondary sulfonamides showed promising enzyme inhibitory effects on AChE while primary sulfonamide derivative was generally effective on hCA I and hCA II isoenzymes.
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http://dx.doi.org/10.3906/kim-2007-37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763114PMC
December 2020

Synthesis and bioactivities of 1-(4-hydroxyphenyl)-2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors.

Turk J Chem 2020 18;44(4):1058-1067. Epub 2020 Aug 18.

Department of Chemistry, Faculty of Science, Atatürk University, Erzurum Turkey.

The discovery of enzyme targeting inhibitors is a popular area of drug research. Biological activities of the compounds bearing phenol and heteroaryl groups make them popular groups in drug design targeting important enzymes such as acetylcholinesterase (AChE, E.C.3.1.1.7) and carbonic anhydrases (CAs, EC 4.2.1.1). 1-(4-hydroxyphenyl)- 2-((aryl)thio)ethanones as possible AChE and CAs inhibitors were synthesized, and their chemical structures were confirmed by IR, H NMR, C NMR, and HRMS. The compounds 2 and 4 were found potent AChE inhibitors with the Ki values of 22.13 ±1.96 nM and 23.71 ±2.95 nM, respectively, while the compounds 2 (Ki = 8.61 ±0.90 nM, on hCA I) and 1 (Ki = 8.76 ±0.84 nM, on hCA II) had considerable CAs inhibitory potency. The lead compounds may help the scientists for the rational designing of an innovative class of drug candidates targeting enzyme-based diseases.
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http://dx.doi.org/10.3906/kim-2004-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751916PMC
August 2020

In vitro Antioxidant and Cytotoxic Activities of Extracts of Endemic Tanacetum erzincanense Together with Phenolic Content by LC-ESI-QTOF-MS.

Chem Biodivers 2021 Mar 8;18(3):e2000812. Epub 2021 Feb 8.

Erzincan University, Faculty of Science, Department of Chemistry, 24100, Erzincan, Turkey.

In this study, phenolic composition, and in vitro biological activities of ethyl acetate (EAE) and methanol (ME) extracts obtained from the aerial parts of endemic Tanacetum erzincanense were investigated. Total phenolic and flavonoid content of the extracts were determined by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Antioxidant capacity of the extracts was evaluated over radical scavenging (DPPH and ABTS) and metal ion reducing power (FRAP and CUPRAC) tests. Individual phenolic compounds in ME was analyzed by high-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF/MS). Cell inhibitory potential of the extracts was tested against colorectal adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7), and hepatocarcinoma (HepG2) cells by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The results showed that ME contains higher TPC (64.4 mg GAE/g) and TFC (62.2 mg QE/g) than those of EAE (41.5 mg GAE/g and 40.0 mg QE/g). LC-ESI-QTOF/MS analysis revealed that ME is rich in phenolic compounds, namely, chlorogenic acid, apigenin, quercetin, luteolin, and diosmetin. Antioxidant assay results indicated that ME possess stronger activity than EAE and a power that competes with synthetic antioxidants. XTT assay results demonstrated that although both extracts displayed a considerable cytotoxicity against the tested cancer cell lines in a time and dose-dependent manner, ME expressed its selective inhibitory action towards MCF-7 cells with an IC value of 20.4 μg/mL for 72 h. These results may serve as a basis for further in vivo studies to examine the potential applications of T. erzincanense in food and pharmaceutical industries.
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http://dx.doi.org/10.1002/cbdv.202000812DOI Listing
March 2021

Synthesis, characterization, crystal structure, α-glycosidase, and acetylcholinesterase inhibitory properties of 1,3-disubstituted benzimidazolium salts.

Arch Pharm (Weinheim) 2021 May 11;354(5):e2000422. Epub 2021 Jan 11.

Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey.

Chloro-/fluorobenzyl-substituted benzimidazolium salts were synthesized from the reaction of 4-fluorobenzyl/2-chloro-4-fluorobenzyl-substituted benzimidazole and chlorinated aromatic hydrocarbons. They were characterized using various spectroscopic techniques (Fourier-transform infrared and nuclear magnetic resonance) and elemental analysis. In addition, the crystal structures of the complexes 1a -d and 2b were determined by single-crystal X-ray diffraction methods. These compounds were crystallized in the triclinic crystal system with a P-1 space group. The crystal packing of all complexes is dominated by O-H⋯Cl hydrogen bonds, which link the water molecules and chloride anions, forming a chloride-water tetrameric cluster. These synthesized salts were found to be effective inhibitors for α-glycosidase and acetylcholinesterase (AChE), with K values ranging from 45.77 ± 6.83 to 102.61 ± 11.56 µM for α-glycosidase and 0.94 ± 0.14 to 10.24 ± 1.58 µM for AChE. AChE converts acetylcholine into choline and acetic acid, thus causing the return of a cholinergic neuron to its resting state. Discovering AChE and α-glycosidase inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease and diabetes.
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http://dx.doi.org/10.1002/ardp.202000422DOI Listing
May 2021

Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes.

Bioorg Chem 2021 Feb 15;107:104554. Epub 2020 Dec 15.

Department of Chemistry, Faculty of Science, Ataturk University, 25240 Erzurum, Turkey.

With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Ks varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bioorg.2020.104554DOI Listing
February 2021

Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives.

Int J Biol Macromol 2021 Feb 19;170:1-12. Epub 2020 Dec 19.

Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey.

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K values in the range of 19.28-135.88 nM for α-glycosidase (K value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (K value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (K value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (K value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (K value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.121DOI Listing
February 2021

Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone-based benzenesulfonamides.

Arch Pharm (Weinheim) 2021 Apr 7;354(4):e2000375. Epub 2020 Dec 7.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

New imidazolinone-based benzenesulfonamides 3a-e and 4a-e were synthesized in three steps and their chemical structures were confirmed by H NMR (nuclear magnetic resonance), C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas 3d and 4a were leads against hCA II in terms of K values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3-4.8 times more selective inhibitors than their corresponding analogues 3a-d in series 3, in which hydrogen was located in place of the nitro group, by considering K values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest K values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.
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http://dx.doi.org/10.1002/ardp.202000375DOI Listing
April 2021

Metal contained Phthalocyanines with 3,4-Dimethoxyphenethoxy substituents: their anticancer, antibacterial activities and their inhibitory effects on some metabolic enzymes with molecular docking studies.

J Biomol Struct Dyn 2020 Nov 24:1-12. Epub 2020 Nov 24.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

The compounds (-) used in this study were re-synthesized in accordance with our previous study. The inhibitory effect of the complexes on some metabolic enzymes was examined and it was demonstrated that the enzymes inhibited by ligands and their complex molecules at micromolar level. The best Ki value for α-glycosidase enzyme was absorved 1.01±0.08 µM for compound . The biological activity of ligand and metal complexes against enzymes was compared with molecular docking method. The enzymes used against ligand and metal complexes respectively: Achethylcholinesterase for ID 4M0E (AChE), butyrylcholinesterase for ID 5NN0 (BChE), α-glycosidase for ID 1XSI (α-Gly). ADME analysis was performed to examine the drug properties of the compounds (-). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The and compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds ( and ). Furthermore, antibacterial activities of these compounds against and were examined. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1844051DOI Listing
November 2020

Novel quinazolin-sulfonamid derivatives: synthesis, characterization, biological evaluation, and molecular docking studies.

J Biomol Struct Dyn 2020 Nov 23:1-12. Epub 2020 Nov 23.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin-sulfonamid derivatives () were synthesized, characterized and evaluated for their antidiabetic, anticholinergics, and antiepileptic activity. These synthesized novel quinazolin-sulfonamid derivatives () were found to be effective inhibitor molecules for the α-glycosidase, human carbonic anhydrase I and II (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzyme, with Ki values in the range of 100.62 ± 13.68-327.94 ± 58.21 nM for α-glycosidase, 1.03 ± 0.11-14.87 ± 2.63 nM for hCA I, 1.83 ± 0.24-15.86 ± 2.57 nM for hCA II, 30.12 ± 3.81-102.16 ± 13.87 nM for BChE, and 26.16 ± 3.63-88.52 ± 20.11 nM for AChE, respectively. In the last step, molecular docking calculations were made to compare biological activities of molecules against enzymes which are achethylcholinesterase, butyrylcholinesterase and α-glycosidase. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1847193DOI Listing
November 2020

Synthesis of benzamide derivatives with thiourea-substituted benzenesulfonamides as carbonic anhydrase inhibitors.

Arch Pharm (Weinheim) 2021 Feb 12;354(2):e2000230. Epub 2020 Oct 12.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

The novel compounds with the chemical structure of N-({4-[N'-(substituted)sulfamoyl]phenyl}carbamothioyl)benzamide (1a-g) and 4-fluoro-N-({4-[N'-(substituted)sulfamoyl]phenyl}carbamothioyl)benzamide (2a-g) were synthesized as potent and selective human carbonic anhydrase (hCA) I and hCA II candidate inhibitors. The aryl part was changed to sulfacetamide, sulfaguanidine, sulfanilamide, sulfathiazole, sulfadiazine, sulfamerazine, and sulfametazine. The K values of compounds 1a-g were in the range of 20.73 ± 4.32 to 59.55 ± 13.07 nM (hCA I) and 5.69 ± 0.43 to 44.81 ± 1.08 nM (hCA II), whereas the K values of compounds 2a-g were in the range of 13.98 ± 2.57 to 75.74 ± 13.51 nM (hCA I) and 8.15 ± 1.5 to 49.86 ± 6.18 nM (hCA II). Comparing the K values of the final compounds and acetazolamide, compound 1c with the sulfanilamide moiety (K  = 5.69 ± 0.43 nM, 8.8 times) and 2f with the sulfamerazine moiety (K  = 8.15 ± 1.5 nM, 6.2 times) demonstrated promising and selective inhibitory effects against the hCA II isoenzyme, the main target protein in glaucoma. Furthermore, compounds 1d (K  = 20.73 ± 4.32, 4 times) and 2d (K  = 13.98 ± 2.57, 5.9 times), which have the sulfathiazole moiety, were found as potent hCA I inhibitors. Compounds 1c and 2f can be considered as the lead compounds determined in the present study, which can be investigated further to alleviate glaucoma symptoms.
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http://dx.doi.org/10.1002/ardp.202000230DOI Listing
February 2021

Concise syntheses and some biological activities of dl-2,5-di-O-methyl-chiro-inositol, dl-1,4-di-O-methyl-scyllo-inositol, and dl-1,6-dibromo-1,6-dideoxy-2,5-di-O-methyl-chiro-inositol.

Arch Pharm (Weinheim) 2021 Feb 30;354(2):e2000254. Epub 2020 Sep 30.

Department of Chemistry, Faculty of Sciences and Arts, Ordu University, Ordu, Turkey.

The regio- and stereospecific synthesis of O-methyl-chiro-inositols and O-methyl-scyllo-inositol was achieved, starting from p-benzoquinone. After preparing dimethoxy conduritol-B as a key compound, regiospecific bromination of the alkene moiety of dimethoxy conduritol-B and acid-catalyzed ring opening of dimethoxydiacetate conduritol-B epoxide with Ac O afforded the desired new chiro-inositol derivatives and scyllo-inositol derivative, respectively. Spectroscopic methods were employed for the characterization of all synthesized compounds. The novel inositols (11-17) had effective inhibition profiles against human carbonic anhydrase isoenzymes I and II (hCA I and II) and acetylcholinesterase (AChE). The novel inositols 11-17 were found to be effective inhibitors against AChE, hCA I, and hCA II enzymes. K values were calculated in the range of 87.59 ± 7.011 to 237.95 ± 17.75 μM for hCA I, 65.08 ± 12.39 to 538.98 ± 61.26 μM for hCA II, and 193.28 ± 43.13 to 765.08 ± 209.77 μM for AChE, respectively. Also, due to the inhibitory effects of the novel inositols 11-17 against the tested enzymes, these novel inositols are potential drug candidates to treat some diseases such as glaucoma, epilepsy, leukemia, and Alzheimer's disease.
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http://dx.doi.org/10.1002/ardp.202000254DOI Listing
February 2021

Synthesis and in silico studies of triazene-substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors.

Arch Pharm (Weinheim) 2021 Jan 28;354(1):e2000243. Epub 2020 Sep 28.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by H nuclear magnetic resonance (NMR), C NMR, and high-resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, the K values of the compounds 1-9 were in the range of 19.9 ± 1.5 to 96.5 ± 20.7 nM against AChE. Tacrine was used as the reference drug and its K value was 49.2 ± 2.7 nM against AChE. The K values of the compounds 1-9 were in the range of 10.2 ± 2.6 to 101.4 ± 27.8 nM against hCA I, whereas they were 18.3 ± 4.4 to 48.1 ± 4.5 nM against hCA II. Acetazolamide was used as a reference drug and its K values were 72.2 ± 5.4 and 52.2 ± 5.7 nM against hCA I and hCA II, respectively. The most active compounds, 1 (nonsubstituted) against AChE, 5 (4-ethoxy-substituted) against hCA I, and 8 (4-bromo-substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.
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http://dx.doi.org/10.1002/ardp.202000243DOI Listing
January 2021

Phthalocyanine complexes with (4-isopropylbenzyl)oxy substituents: preparation and evaluation of anti-carbonic anhydrase, anticholinesterase enzymes and molecular docking studies.

J Biomol Struct Dyn 2020 Sep 21:1-9. Epub 2020 Sep 21.

Department of Chemistry, Sakarya University, Sakarya, Turkey.

In this study, the preparation, aggregation behavior and investigation of carbonic anhydrase and cholinesterase enzyme inhibition features of non-peripherally (4-isopropylbenzyl)oxy-substituted phthalocyanines () are reported for the first time. The chemical structures of these new phthalocyanines were elucidated by UV-Vis (ultraviolet-visible), FT-IR (Fourier transform infrared spectrometry), NMR (nuclear magnetic resonance) and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry. The substitution of 4-isopropylbenzyl)oxy groups benefits a remarkable solubility and redshift of the phthalocyanines Q-band. Also, these complexes were tested against some enzymes such as butyrylcholinesterase enzyme, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme. The phthalocyanine complexes showed Ki values of in the range of 478.13 ± 57.25-887.25 ± 101.20 µM against hCA I, 525.16 ± 45.87-921.14 ± 81.25 µM against hCA II, 68.33 ± 9.13-201.15 ± 35.86 µM against AChE and 86.25 ± 13.65-237.54 ± 24.7 µM against BChE. Molecular docking studies were performed to investigate the binding modes and interaction energies of the () complexes with the hCA I (PDB ID:1BMZ), hCA II (PDB ID:2ABE), AChE (PDB ID:4EY6) and BChE (PDB ID:2PM8).
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http://dx.doi.org/10.1080/07391102.2020.1818623DOI Listing
September 2020

Synthesis of nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds - Determination of their carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase and α-glycosidase inhibition properties.

Bioorg Chem 2020 10 26;103:104171. Epub 2020 Aug 26.

Dipartimento di Chimica Ugo Schiff, Universita degli Studi di Firenze, Sesto Fiorentino, Firenze, Italy; Neurofarba Department and Laboratorio di Chimica Bioinorganica Universita' degli Studi di Firenze, Sesto Fiorentino, Italy.

Sulfur-containing pyrroles (1-3), tris(2-pyridyl)phosphine(selenide) sulfide (4-5) and 4-benzyl-6-(thiophen-2-yl)pyrimidin-2-amine (6) were synthesized and characterized by elemental analysis, IR and NMR spectra. In this study, the synthesized compounds of nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds (1-6) were evaluated against the human erythrocyte carbonic anhydrase I, and II isoenzymes, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase enzymes. The synthesized heterocyclic compounds showed IC values in range of 33.32-60.79 nM against hCA I, and 37.05-66.64 nM against hCA II closely associated with various physiological and pathological processes. On the other hand, IC values were found in range of 13.13-22.21 nM against AChE, 0.54-31.22 nM against BChE, and 13.51-26.55 nM against α-glycosidase as a hydrolytic enzyme. As a result, nitrogen, phosphorus, selenium and sulfur-containing heterocyclic compounds (1-6) demonstrated potent inhibition profiles against indicated metabolic enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly in the treatment of some global disorders including glaucoma, Alzheimer's disease and diabetes.
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http://dx.doi.org/10.1016/j.bioorg.2020.104171DOI Listing
October 2020

Molecular docking and inhibition profiles of some antibiotics on lactoperoxidase enzyme purified from bovine milk.

J Biomol Struct Dyn 2020 Aug 28:1-10. Epub 2020 Aug 28.

Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey.

Antibiotics are generally used for human and veterinary applications to preserve and to control microbial diseases. Milk has a biologically significant enzyme known as lactoperoxidase (LPO) that is a member of peroxidase family. In metabolism, LPO has ability to catalyze the transformation of thiocyanate (SCN) to hypothiocyanite (OSCN) that is an antibacterial agent and the reaction occurs with hydrogen peroxide. In this work, LPO inhibition effects of some antibiotics including cefazolin, oxytetracycline, flunixin meglumine, cefuroxime, tylosin, vancomycin, chloramphenicol and lincomycin were tested. Among the antibiotics cefazolin was indicated the strongest inhibitory efficacy. The half maximal inhibitory concentration (IC) and the inhibition constant (K) values of cefazolin were found as 8.19 and 34.66 µM, respectively. It was shown competitive inhibition. 5-Methyl-1,3,4-thiadiazol-2-yl moiety activity plays a key role in the inhibition mechanism of cefazolin. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1814416DOI Listing
August 2020

Design, synthesis, characterization, biological evaluation, and molecular docking studies of novel 1,2-aminopropanthiols substituted derivatives as selective carbonic anhydrase, acetylcholinesterase and α-glycosidase enzymes inhibitors.

J Biomol Struct Dyn 2020 Aug 27:1-13. Epub 2020 Aug 27.

Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, Turkey.

In the article, various substituted derivatives of 1,2-aminopropanthiol () have been prepared by a general and efficient method, in one-steps, starting from available thiirane and aromatic amines (aniline, -toluidine) as a convenient source of sulfur and nitrogen. The synthesized compounds were fully characterized by spectral and analytical data. Seven novel compounds are synthesized. The biochemical properties indicating their potential for constituting an anti-Alzheimer's disease substance were also recorded revealing strong carbonic anhydrase I, and II, α-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives () were found to be effective inhibitors for the α-glycosidase, human carbonic anhydrase I and II, and acetylcholinesterase enzymes, with K values in the range of 11.47 ± 0.87-24.09 ± 6.37 µM for α-glycosidase, 29.30 ± 4.67-79.01 ± 4.49 µM for hCA I, 14.27 ± 2.82-30.85 ± 12.24 µM for hCA II and 5.76 ± 1.55-55.39 ± 2.27 µM for AChE, respectively. In the last step of this study, molecular docking calculations were obtained in order to compare the biological activities of indicated molecules against the enzymes of acetylcholinesterase, butyrylcholinesterase and α-glycosidase. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1811772DOI Listing
August 2020

Determination of the inhibition profiles of pyrazolyl-thiazole derivatives against aldose reductase and α-glycosidase and molecular docking studies.

Arch Pharm (Weinheim) 2020 Dec 6;353(12):e2000118. Epub 2020 Aug 6.

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl)thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.
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http://dx.doi.org/10.1002/ardp.202000118DOI Listing
December 2020

Synthesis, characterization, powder X-ray diffraction analysis, thermal stability, antioxidant properties and enzyme inhibitions of M(II)-Schiff base ligand complexes.

J Biomol Struct Dyn 2020 Aug 5:1-8. Epub 2020 Aug 5.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

The Schiff base ligand (()-6-methyl-2-(2,3,4-trimethoxybenzylideneamino)-4,5,6,7-tetrahydrobenzo[]thiophene-3-carbonitrile) and its cobalt(II) and palladium(II) complexes were successfully prepared. The structure of the compounds was elucidated by various techniques (NMR, FT-IR, powder X-ray diffraction, microanalysis, TGA, magnetic susceptibility, mass spectrometry). The Pd(II) complex showed a square planar geometry and the Co(II) complex had an octahedral geometry. ABTS (2,2-azino-bis 3-ethylbenzothiazloine-6-sulphonic acid), DPPH (1,1-diphenyl-2-picrylhydrazyl), FRAP (ferric-reducing antioxidant power) and CUPRAC (cupric reducing antioxidant capacity) methods were applied to identify the antioxidant features of the synthesized compounds. In addition, glutathione S-transferase and acetyl/butyryl cholinesterase enzymes were examined for possible inhibition capacities of the complexes. According to the enzyme activity measurements, Ru(II) complex inhibited both GST and BChE enzymes, while Fe(II) complex inhibited only AChE enzyme. Furthermore, the antioxidant activities and enzyme inhibitions of the previously synthesized Fe(II) and Ru(II) complexes of the same ligand were examined to make a comparison of the metal complexes. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1802340DOI Listing
August 2020

Benzenesulfonamide derivatives as potent acetylcholinesterase, α-glycosidase, and glutathione S-transferase inhibitors: biological evaluation and molecular docking studies.

J Biomol Struct Dyn 2020 Jul 21:1-12. Epub 2020 Jul 21.

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

Sulfonamide derivatives exhibit a wide biological activity and can function as potential medical molecules in the development of a drug. Studies have reported that the compounds have an effect on many enzymes. In this study, the derivatives of amine sulfonamide (-) were prepared with reduced imine compounds (-) with NaBH in methanol. The synthesized compounds were fully characterized by spectral data and analytical. The effect of the synthesized derivatives on acetylcholinesterase (AChE), glutathione S-transferase (GST) and α-glycosidase (α-GLY) enzymes were determined. For the AChE and α-GLY, the most powerful inhibition was observed on and series with value in the range 2.26 ± 0.45-3.57 ± 0.97 and 95.73 ± 13.67-102.45 ± 11.72 µM, respectively. values of the series for GST were found in the range of 22.76 ± 1.23-49.29 ± 4.49. Finally, the compounds have a stronger inhibitor in lower concentrations by the attachment of functional electronegative groups such as two halogens (-Br and -CI), -OH to the benzene ring and -SONH. The crystal structures of AChE, α-GLY, and GST in complex with selected derivatives and show the importance of the functional moieties in the binding modes within the receptors. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1790422DOI Listing
July 2020

Cytotoxic effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives.

J Biomol Struct Dyn 2020 Jul 21:1-12. Epub 2020 Jul 21.

Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey.

Today, interest in studies on the search for new drugs to be used in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes, as well as prevention of microbial inflammation is increasing day by day. Emerging biological and pharmacological effects of sulfonyl hydrazone derivative compounds reveal their importance. In the present study, heteroatom-containing sulfonyl hydrazone derivatives have been studied for their anticancer and antimicrobial properties, as well as their effects on enzymes that could play roles in Alzheimer's dissease and diabetes. High doses of the tested compounds significantly decreased the cell viabilities of breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Furthermore, all compounds possessed antimicrobial activities against very common bacteria and . These compounds were good inhibitors of the α-glycosidase, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme with values in the range of 1.14 ± 0.14-3.63 ± 0.26 nM for α-glycosidase, 66.05 ± 9.21-125.45 ± 11.54 nM for hCA I, 89.14 ± 10.43-170.22 ± 26.05 nM for hCA II and 754.03 ± 73.22-943.92 ± 58.15 nM for AChE, respectively. Molecular docking method was used to theoretically compare biological activities of sulfonyl hydrazone derivatives against enzymes. The theoretical results were compared with the experimental results. Thus, these compounds have strong biological activities. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1792345DOI Listing
July 2020

Synthesis, characterization, molecular docking, and biological activities of coumarin-1,2,3-triazole-acetamide hybrid derivatives.

Arch Pharm (Weinheim) 2020 Oct 9;353(10):e2000109. Epub 2020 Jul 9.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin-1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin-1,2,3-triazole-acetamide hybrids showed K values in the range of 483.50-1,243.04 nM against hCA I, 508.55-1,284.36 nM against hCA II, 24.85-132.85 nM against AChE, 27.17-1,104.36 nM against BChE, 590.42-1,104.36 nM against α-Gly, and 55.38-128.63 nM against α-Amy. The novel coumarin-1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin-1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.
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http://dx.doi.org/10.1002/ardp.202000109DOI Listing
October 2020

human monoamine oxidase (hMAO) A and hMAO B inhibitors from Artemisia dracunculus L. herniarin and skimmin: human mononamine oxidase A and B inhibitors from A. dracunculus L.

Z Naturforsch C J Biosci 2020 Nov;75(11-12):459-466

Department of Chemistry, Faculty of Science and Letters, Kilis 7 Aralik University, Kilis 79000, Turkey.

The aim of this study was to investigate the effects of extracts and pure Artemisia dracunculus L. (tarragon) metabolites on the antimonoamine oxidase and anticholinesterase activities. The compounds were characterized as stigmasterol (1), herniarin (2), (2E,4E)-1-(piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4), 3,4-dehydroherniarin (5) and skimmin (6) by 1H-NMR, 13C-NMR, 1D and 2D NMR methods. The compounds 5 and 6 were isolated from tarragon for the first time. The extracts and pure compounds have inhibitory effects on the human monoamine oxidase (hMAO) A and B enzymes, whereas they did not exhibit any anticholinesterase activities. Among the tarragon compounds, only 2 and 6 compounds showed the inhibitory effects against hMAO A (IC50 = 51.76 and 73.47 μM, respectively) and hMAO B (IC50 = 0.84 and 1.63 mM, respectively). In the study, herniarin content in the extracts was also analysed by high-performance liquid chromatography and it was found that there was a relationship between the inhibition effects of the extracts and their herniarin content.
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http://dx.doi.org/10.1515/znc-2019-0227DOI Listing
November 2020

N-Substituted pyrimidinethione and acetophenone derivatives as a new therapeutic approach in diabetes.

Arch Pharm (Weinheim) 2020 Sep 14;353(9):e2000075. Epub 2020 Jun 14.

Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey.

In this study, compounds with 4-hydroxybutyl, 4-phenyl, 5-carboxylate, and pyrimidine moieties were determined as α-glycosidase inhibitors. N-Substituted pyrimidinethione and acetophenone derivatives (A1-A5, B1-B11, and C1-C11) were good inhibitors of the α-glycosidase enzyme, with K values in the range of 104.27 ± 15.75 to 1,004.25 ± 100.43 nM. Among them, compound B7 was recorded as the best inhibitor, with a K of 104.27 ± 15.75 nM against α-glycosidase. In silico studies were carried out to clarify the binding affinity and interaction mode of the compounds with the best inhibition score against α-glycosidase from Saccharomyces cerevisiae. Compounds B7 (S) and B11 (R) exhibited a good binding affinity with docking scores of -8.608 and 8.582 kcal/mol, respectively. The docking results also showed that the 4-hydroxybutyl and pyrimidinethione moieties play a key role in S. cerevisiae and human α-glycosidase inhibition.
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http://dx.doi.org/10.1002/ardp.202000075DOI Listing
September 2020

Quinoline-based promising anticancer and antibacterial agents, and some metabolic enzyme inhibitors.

Arch Pharm (Weinheim) 2020 Sep 14;353(9):e2000086. Epub 2020 Jun 14.

Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey.

A series of substituted quinolines was screened for their antiproliferative, cytotoxic, antibacterial activities, DNA/protein binding affinity, and anticholinergic properties by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation, lactate dehydrogenase cytotoxicity, and microdilution assays, the Wolfe-Shimmer equality method, the Ellman method, and the esterase assay, respectively. The results of the cytotoxic and anticancer activities of the compounds displayed that 6-bromotetrahydroquinoline (2), 6,8-dibromotetrahydroquinoline (3), 8-bromo-6-cyanoquinoline (10), 5-bromo-6,8-dimethoxyquinoline (12), the novel N-nitrated 6,8-dimethoxyquinoline (13), and 5,7-dibromo-8-hydroxyquinoline (17) showed a significant antiproliferative potency against the A549, HeLa, HT29, Hep3B, and MCF7 cancer cell lines (IC  = 2-50 μg/ml) and low cytotoxicity (∼7-35%) as the controls, 5-fluorouracil and cisplatin. The compound-DNA linkages are hyperchromic or hypochromic, causing variations in their spectra. This situation shows that they can be bound to DNA with the groove-binding mode, with K value in the range of 2.0 × 10 -2.2 × 10  M . Studies on human Gram(+) and Gram(-) pathogenic bacteria showed that the substituted quinolines exhibited selective antimicrobial activities with MIC values of 62.50-250 μg/ml. All tested quinoline derivatives were found to be effective inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase I and II isoforms (hCA I and II), with K values of 46.04-956.82 nM for hCA I, 54.95-976.93 nM for hCA II, and 5.51-155.22 nM for AChE. As a result, the preliminary data showed that substituted quinolines displayed effective pharmacological features. Molecular docking studies were performed to investigate the binding modes and interaction energies for compounds 2-17 with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).
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http://dx.doi.org/10.1002/ardp.202000086DOI Listing
September 2020

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3-diaryltriazene-substituted sulfathiazole derivatives.

Arch Pharm (Weinheim) 2020 Sep 11;353(9):e2000102. Epub 2020 Jun 11.

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

In the present study, a series of eleven novel 1,3-diaryltriazene-substituted sulfathiazole moieties (ST1-11) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, H-NMR (nuclear magnetic resonance), C-NMR, and high-resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α-glycosidase (α-GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), with K values in the range of 426.84 ± 58.42-708.61 ± 122.67 nM for α-GLY, 450.37 ± 50.35-1,094.34 ± 111.37 nM for hCA I, 504.37 ± 57.22-1,205.36 ± 195.47 nM for hCA II, and 68.28 ± 10.26-193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4-[3-(perfluorophenyl)triaz-1-en-1-yl]-N-(thiazol-2-yl)benzenesulfonamide) showed a highly efficient inhibition profile against hCA I, hCA II, and AChE, with K values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes.
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http://dx.doi.org/10.1002/ardp.202000102DOI Listing
September 2020

Novel propanolamine derivatives attached to 2-metoxifenol moiety: Synthesis, characterization, biological properties, and molecular docking studies.

Bioorg Chem 2020 08 24;101:103969. Epub 2020 May 24.

Department of Chemistry, Faculty of Science, Ataturk University, 25240 Erzurum, Turkey.

The synthesis of seven new ß-amino alcohols was designed and performed by starting from eugenol, a natural phenolic compound known to be biologically active. The synthesized compounds were obtained in yields ranging from 54 to 81%. Molecule structures were determined with FT-IR, H NMR and C NMR spectroscopies. In addition, the inhibitory effects of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes have been investigated. It has been seen that all compounds have a better ability to inhibit compared to existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 2b (Ki 62.08 ± 11.67 µM and IC 90.33), and against α-Gly, 2c showed the highest effect (Ki 0.33 ± 0.08 µM and IC 0.28). The best inhibitor against hCA I, and hCA II enzymes is compound 2f. For hCA I and hCA II, Ki value was measured as 9.68 ± 1.32 and 11.46 ± 2.64 µM and IC values as 7.37 and 8.26 µM respectively. The interactions of the studied new propanolamine derivatives with the enzymes were done by molecular docking calculations and their biological activities were compared to the experimental tests. Studied enzymes in molecular docking calculations are acetylcholinesterase (AChE) is PDB ID: 4M0E, α-glycosidase (α-Gly) is PDB ID: 1R47, human carbonic anhydrase isoenzyme I (hCA I) PDB ID: 3LXE is human carbonic anhydrase isoenzyme II (hCA II) is PDB ID: 5 AML.
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http://dx.doi.org/10.1016/j.bioorg.2020.103969DOI Listing
August 2020