Influence of Chirality of Benzimidazole Amine Hybrids on Inhibition of Human Erythrocytes Carbonic Anhydrase I, II and Acetylcholinesterase

Novel chiral benzimidazole amine hybrids (4a–4d) were synthesized from commercially available amine [(R)- (+)-phenylethylamine, (−) (S)-(-)-phenylethylamine, (−) (R)-(-)-cyclohexylethylamine, (S)-(+)-cyclohexylethylamine] and 2-(chloromethyl)-N-tosyl-1H-benzimidazole. The synthesized compounds (4a–4d) were characterized by IR, NMR, and LC/MS analysis. The inhibitory effect of 4a–4d on human erythrocytes carbonic anhydrase I (hCA-I), II (hCA-II), and acetylcholinesterase (AChE) activity was investigated. For hCA-I, the IC50 values of 4a–4d were found to be 4.895 μM, 1.750 μM, 0.173 μM, and 0.620 μM, respectively, and for hCA-II, the IC50 values of 4a–4d were found to be 0.469 μM, 0.380 μM, 0.233 μM, 0.635 μM, respectively. Furthermore, IC50 values of 4a–4d on AChE were found as 87.5 nM, 100 nM, 26.92 nM, and 100 nM, respectively. In addition, molecular docking analysis was performed to evaluate the affinity of 4a–4d against hCA-I, hCA-II, and AChE and explain their binding interactions. © 2023 Wiley-VHCA AG, Zurich, Switzerland

Synthesis of benzimidazole derivatives containing amide bond and biological evaluation as acetylcholinesterase, carbonic anhydrase I and II inhibitors

Acetylcholinesterase (AChE) and carbonic anhydrase I (CA-I) and II (CA-II) are two vital metabolic enzymes. AChE inhibitors are seen as target molecules in drug development studies for Alzheimer's treatment. CA inhibitors are target molecules for treating many diseases from glaucoma to cancer. For this reason, it is crucial to identify new AChE and CA inhibitors. In this study, four benzimidazole acetamide derivatives were synthesized and their inhibition effects were investigated against human erythrocyte carbonic anhydrase I (hCA-I), II (hCA-II), and AChE. IC50 values of 9a-10b were determined in the range of 0.936 to 17.07 µM for AChE. IC50 values of 9a–10b for hCA-I were found as 7.21 µM, 4.72 µM, 6.08 µM, 8.23 µM, respectively. On the other hand, IC50 values of 9a–9b for hCA-II were found as 8.64 µM, 7.07 µM, 4.12 µM, 5.93 µM, respectively. According to IC50 values, 9a–10b molecules exhibited strong inhibition effects for AChE and hCAI, II. Also, Molecular docking studies were carried out to explain the binding interaction of 9a–10b with AChE, hCA-I, and hCA-II. © 202

In vitro anti-leishmanial activities and structure-activity relationship analysis of new antimony(III) complexes

1609-1617New fourteen antimony(III) complexes of general formula [SbLnCl3] (where n= 1 or 2, L =2-aminopyridine, 5-methyl-2-aminopyridine, 2-aminopyrimidine, 4,6-dimethoxy-2-aminopyrimidine, 2-benzyl-2-thiopseudeourea,2-guanidinobenzimidazole, 2-amino-5-thiol-4,6-dimethoxypyrimidine, 2-amino-5-(1H-tetrazol-5-ylthio)-4,6-dimethoxypyrimidine, N-2-pyrimidine, 2-piperidinecarboxamide, N-2-pyrimidine, 2-pyrrolidinecarboxamide, 2-amino-5-(1H-tetrazol-5-iltiyo)-4,6-dimethoxypyrimidine-2-pyrrolidinecarboxamide and N-2-pyrimidine, 5-chloro-2-thiophenecarboxamide, N-2-benzothiazol-2-pyrrolidinecarboxaamide, N,N-(1,2-phenyl)dipyrrolidine-2-carboxamide) have been synthesized and their anti-leishmanial activity have been assessed in vitro against Leishmania tropica promastigotes. The best complex, Sb(2-guanidinobenzimidazole)Cl3 is demostrated 3.16% growth inhibition at a concentration of 31.25 μg/mL. In general, antimony(III) complexes containing pyrimidine ligands has showed higher anti-leishmanial activity than antimony(III) complexes bearing pyridine ligands, and electron-donating substituents decrease the anti-leishmanial activity. All complexes have been optimised with DFT/B3LYP/LANL2DZ method in the gas phase. Several descriptors are tested to find a quantitative correlation between anti-leishmanial activity and structural properties of the complexes by best multiple linear regression method. Good correlations are obtained with minimum net atomic charge for a C atom and maximum bond order of a Cl atom. The developed QSAR equation is internally validated

In vitro anti-leishmanial activities and structure-activity relationship analysis of new antimony(III) complexes

New fourteen antimony(III) complexes of general formula [SbLnCl3] (where n= 1 or 2, L =2-aminopyridine, 5-methyl-2-aminopyridine, 2-aminopyrimidine, 4,6-dimethoxy-2-aminopyrimidine, 2-benzyl-2-thiopseudeourea,2-guanidinobenzimidazole, 2-amino-5-thiol-4,6-dimethoxypyrimidine, 2-amino-5-(1H-tetrazol-5-ylthio)-4,6-dimethoxypyrimidine, N-2-pyrimidine, 2-piperidinecarboxamide, N-2-pyrimidine, 2-pyrrolidinecarboxamide, 2-amino-5-(1H-tetrazol-5-iltiyo)-4,6-dimethoxypyrimidine-2-pyrrolidinecarboxamide and N-2-pyrimidine, 5-chloro-2-thiophenecarboxamide, N-2-benzothiazol-2-pyrrolidinecarboxaamide, N,N-(1,2-phenyl)dipyrrolidine-2-carboxamide) have been synthesized and their anti-leishmanial activity have been assessed in vitro against Leishmania tropica promastigotes. The best complex, Sb(2-guanidinobenzimidazole)Cl3 is demostrated 3.16% growth inhibition at a concentration of 31.25 μg/mL. In general, antimony(III) complexes containing pyrimidine ligands has showed higher anti-leishmanial activity than antimony(III) complexes bearing pyridine ligands, and electron-donating substituents decrease the anti-leishmanial activity. All complexes have been optimised with DFT/B3LYP/LANL2DZ method in the gas phase. Several descriptors are tested to find a quantitative correlation between anti-leishmanial activity and structural properties of the complexes by best multiple linear regression method. Good correlations are obtained with minimum net atomic charge for a C atom and maximum bond order of a Cl atom. The developed QSAR equation is internally validated

Acetohydroxyacid Synthase (AHAS) Inhibitor-Based Commercial Sulfonylurea Herbicides as Glutathione Reductase Inhibitors: in Vitro and in Silico Studies

In this study, in vitro inhibitory effect of AHAS inhibiting-based commercial sulfonylurea herbicides on human GR and S. cerevisiae GR was determined by electrochemical method. Our findings, the first report in literature, show that the four commercial herbicides were found to be the inhibitors in the range of 4.90–9.75 μM for ScGR, and in the range of 8.54–18.84 μM for hGR. Global reactivity descriptors (energy gaps, electronegativity, hardness and electrophilicity index) of the herbicides were calculated by DFT/B3LYP/6-31G(d,p) method in gas phase. The electrochemical behavior of the herbicides was studied by cyclic voltammetry. Single-electron half-wave reduction potentials and global reactivity descriptors were correlated with the IC50 values of the herbicides. Molecular docking analysis using Schrödinger Suite was applied to examine the interaction between the herbicides and human GR (PDB ID:1XAN and 2GH5), S. cerevisiae GR (PDB ID:2HQM), P. falciparum GR (PDB ID:1ONF), C. albicans AHAS (PDB ID:6DEL) and ScAHAS (PDB ID: 5FEM. Based on the docking results, it can be predicted that (a) herbicides have similar binding potential to two different binding sites of hGRs, (b) herbicides may have antimalarial potential against P. falciparum (c) herbicides may have antifungal potential against C. albicans. © 2022 Wiley-VCH GmbH

Synthesis of new antimony(III) complexes for treatment of leishmaniasis

Bu çalışmada toplam 24 tane kapalı formülü SbLnX3 olan ( n: 1 veya 2, X: Cl veya Br, L: 2-aminopiridin (1), 2-amino-5-metil piridin (2), 2-amino pirimidin (3), 2-amino-4,6- dimetoksi pirimidin (4), 2-benzil-2-tiyopseudoüre (5), 2-guanidobenzimidazol (6), 2- amino-4,6-dimetoksi-5-tiyol pirimidin (7), 2-amino-5-(1H-tetrazol-5-iltiyo)-4,6-dimetoksi pirimidin (8), 5-5'-disülfanidil-bis(2-amino-4,6 dimetoksipirimidin) (9), N-2-pirimidin-2- piperidinkarboksamit (10), N-2-pirimidin-2-pirolidinkarboksamit (11), N-2-5-(1H-tetrazol- 5-iltiyo)-4,6-dimetoksipirimidin-2-pirolidinkarboksamit (12), 5-kloro-N-(2-pirimidin) tiyofen-2-karboksamit (13), N-2-benzotiyoazol-2-pirolidinkarboksamit (14), N,N-(1,2- fenil)dipirolin-2-karboksamit) (15) antimon(III) kompleksi sentezlenmiş ve yapıları spektroskopik (LC-MS, 1H-NMR, 13C-NMR, FTIR ) yöntemler, elementel analiz ve iletkenlik yöntemi ile aydınlatılmıştır. Ayrıca 9 nolu ligandın yapısı tek kristal X-ışını analizi ile belirlenmiştir. Komplekslerin glutation redüktaz inhibitör aktiviteleri (IC50, Ki) belirlenmiştir. Kompleksleri antileishmania aktiviteleri Aydın şehrindeki bir hastadan izole eden Leishmania tropica promastigotları üzerinde Adnan Menderes Üniversitesi Tıp Fakültesi Parazitoloji bölümünde çalışılmıştır. En yüksek glutation redüktaz inhibitör ve antileishmania aktivitesini Sb(2-guanidobenzimidazol )Br3 kompleksi göstermiştir. Bütün komplekslerin DNA yarılma etkileşimleri yapılmıştır. Oniki adet Sb(III) kompleksinin IC50 (glutation redüktaz aktivitesi) değerleri kullanılarak 2D-QSAR analizi yapılmıştır. Elde edilen denklemde, H atomu üzerindeki maksimum yük arttıkça ve HOMO-LUMO enerji farkı azaldıkça GR aktivitelerinin arttığını öngörmektedir.In this study, a total of twenty-four Sb(III) complexes with molecular formula of SbLnX3 (n: 1 or 2, X: Cl or Br, L: 2-aminopyridine (1), 2-amino-5-methylpyridine (2), 2- aminopyrimidine (3), 2-amino-4,6-dimethoxypyrimidine (4), 2-benzyl-2-thiopseudourea (5), 2-guanidinobenzimidazole (6), 2-amino-4,6-dimethyoxy-5-thiolpyrimidine (7), 2- amino-5-(1H-tetrazole-5-ylthio)-4,6-dimethoxypyrimidine (8), 5-5'-disulfanidyl-bis(2- amino-4,6 dimethoxypyrimidine) (9), N-2-pyrimidine-2-piperidinecarboxamide (10), N-2- pyrimidine-2-prolidinecarboxamide (11), N-2-5-(1H-tetrazol-5-iltiyo)-4,6- dimetoksipirimidin-2-prolinecarboxamide (12), 5-chloro-N-(2-pyrimidine)thiophen-2- carboxamide (13), N-2-benzothiazol-2-prolidinecarboxamide (14), N,N-(1,2-phenyl) diprolidine-2-carboxamide) (15) were synthesized and their structure were identified with spectroscopy methods ((LC-MS, 1H-NMR, 13C-NMR, FTIR ) elemental analysis and conductivity measurements. In addition, the structure of ligand 9 was identified by single crystal X-ray analysis. Glutathione reductase inhibitory activites (IC50, Ki) of all complexes were studied. Antileishmanial activities of the complexes were studied at Adnan Menderes University Medicine Faculty Parasitology Department on Leishmania tropica promastes isolated from a patient in Aydın. Sb(2-guanidobenzimidazole )Br3 has the highest glutathione reductase inhibitory and antileishmanial activites. DNA cleavage interaction of all complexes were carried out. 2D-QSAR analysis were carried out by using IC50 (for glutathione reductase inhibitory activity) values of twelve Sb(III) complexes with and antileishmanial activites. Obtained model equations predict that increase in maximum partial charge for a H and decrease in HOMO-LUMO gap, increase the glutathione inhibitory activity of the complexes

Synthesis and antimicrobial study of new benzimidazole schiff bases bearing P-toluene sulfonamide moiety

Three new Schiff bases bearing benzimidazole and p-toluen sulfonamide moiety were synthesized. Their structures were characterized by elemental analysis, FTIR, NMR and LCMS methods. The antimicrobial properties of the compounds were also evaluated. All compounds exhibit higher antimicrobial activity against all bacteria, Schiff bases (4a-4c) shows more activity than the parent aldehyde (3). 4c displays higher antibacterial activity against P. aeruginosa compare to reference drug Sulfioxazole. The compounds were found more potent against Gram-negative than Gram positive bacteria. One more free phenyl group increase the activity in 4c, but one more phenyl ring in 4b does not.In vitro antifungal activity of the compounds was also tested on fungi C. albicans C. tropicalis and C. krusei. However, our compounds exhibit no antifungal activity against three fungi. © 2019 Sociedad Chilena de Quimica. All rights reserved

A Study Model Aimed at Playing Counterpointal Songs Based Turkish Music in Piano Teaching

Araştırmanın amacı, Türkiyezde piyano öğretiminde kullanılan makamsal içerikli materyallere ilişkin ihtiyaç durumunu belirlemek, piyano öğretiminde Türk Müziği kaynaklı kontrpuantal eserlerin seslendirilmesine yönelik bir çalışma modeli oluşturmak, bu modelin öğrenci başarısı üzerine etkilerini incelemektir. Araştırmanın çalışma grubunu bir devlet üniversitesi konservatuvarında 2013-2014 öğretim yılı bahar döneminde eğitim gören 10 öğrenci oluşturmaktadır. Araştırmada hem betimsel hem deneysel olarak nicel yöntem kullanılmıştır. Betimsel boyutta anket uygulaması yapılmış; deneysel boyutta ise tek grup ön test - son test modeli kullanılmıştır. Araştırma; çokseslilik yöntemlerinden karma armoni yaklaşımıyla, Nihavent ve Nikriz makam dizileri kullanılarak yazılmış kontrpuantal eserler ile sınırlandırılmıştır. Uygulanan anket sonucu elde edilen verilerin çözümlenmesinde frekans (f), yüzde (%) değerleri kullanılmıştır. Deneysel verilerin çözümlenmesinde ise araştırmacı tarafından geliştirilen ölçme aracı kullanılarak elde edilen verilerin analizinde Wilcoxon İşaretli Sıralar Testi kullanılmıştır. Bu sonuçlara göre, Türk Müziği materyalleri kullanılarak yazılan kontrpuantal eserlerin seslendirilmesine yönelik hazırlanan çalışma modelinin, ortaya çıkan kanıtlar sonucu işlevsel olduğu saptanmış ve konuyla ilgili önerilerde bulunulmuştur.The aim of this study is to determine the need for maqamic content materials used in piano teaching in Turkey, form a study model aimed at playing counterpointal pieces based Turkish music in piano teaching and investigate the effects of this model on student achievement. The study group of this research includes 10 students studying in a public university state conservatory in spring term in 2013-2014. Quantitative method is used in the study both descriptively and experimentally. In the descriptive part, questionnaire is conducted and in the experimental part, single group pretest - posttest model is used. The research is limited with counterpointal pieces written in one of the counterpointal methods, mixed harmony, by using Nihavent and Nikriz maqamic scale. In order to analyze the data obtained from the questionnaire, frequency (f) and percent (%) values were used. In order to analyze the experimental data, a measurement tool developed by the researcher was used and Wilcoxon Signed - Rank Test was used to analyze the data. In conclusion, it is understood with the evidences that the study model which was aimed at playing counterpointal pieces written by using Turkish music materials is fully operational and recommendations were given related to the subject matter

INVESTIGATION OF USABILITY SITUATION OF THE PIANO IN HARMONY-COUNTERPOINT-ACCOMPANIMENT COURSES WHICH ARE BEING APPLIED AT THE MUSIC EDUCATION PROGRAMME

Bu araştırma, Müzik Öğretmenliği Programı öğrencilerinin Armoni- Kontrpuan-Eşlik derslerinde piyanoyu kullanabilme durumunu ortaya koymayı amaçlayan betimsel bir çalışma olarak tasarlanmıştır. Problemin çözümü doğrultusunda, öğrencilerin eşlikleyebilme becerisi ile deşifre edebilme becerisini ölçmeye yönelik olarak üç farklı zorluk düzeyinde, 5'er ezgisel çalışma hazırlanmıştır. Basit, orta ve ileri zorluk düzeylerinde yer alan ezgiler, önce basit düzey gurubunda sonra orta düzey gurubunda daha sonra ileri düzey gurubunda olmak üzere birer hafta ara ile öğrencilere çaldırılmış ve video kayıtları alınmıştır. Bu kayıtlar, araştırma kapsamında hazırlanan ölçme araçları kullanılarak uzmanlar tarafından değerlendirilmiş ve öğrenci performansları puanlanmıştır. Değerlendirme sonuçları ise bulgular ve yorum bölümünde tablolar halinde yer verilmiştir. Bulgular ve yorumlar ışığında öğrencilerin Armoni- Kontrpuan-Eşlik derslerinde piyanoyu kullanabilmede güçlük çektiği noktalar tespit edilmiş ve bu noktalara ilişkin önerilerde bulunulmuştur.The purpose of the study is investigation of pre-service Music teachers' performance on using piano in \"Harmony-Counterpoint-Companion\" course. Descriptive statistical methods are used to find solutions. For analyzing the data, according to measuring students' accompanion ability with three different difficulty levels for five melodically study have been prepared for each level. Melodies that have simple, intermediate and advanced levels of difficulty were played by students every week through three weeks. First week students played simple level group of melodies, second week in the mid-level group of melodies, and then third week advanced level group of melodies and video recordings were taken. These students' performance records were evaluated by measuring instruments that was prepared by the reasearcher and also evaluated by experts. Assessment results, findings and comments were included in the table. In the light of results and comments students difficulties in using piano in Harmony- Counterpoint-Accompaniment course had been determined and conclusions were reached

Farklı biçim zamanı ve sayısının (Leucaena leucocephala(lam) de wit.'nın verim ve bazı tarımsal özelliklere etkisi üzerinde bir araştırma

TEZ183Tez (Yüksek Lisans) -- Çukurova Üniversitesi, Adana, 1984.Kaynakça (s. 53-55) var.57 s. ; 28 cm.