Zeynep Soyer

Synthesis and anticonvulsant activity of some 2/3-benzoylaminopropionanilide derivatives.

In this study, the synthesis and anticonvulsant properties of sixteen 2/3-benzoylaminopropionanilide derivatives were described. Molecular design of the compounds has been based on the modification of lacosamide which is a functionalized amino acid with a novel anticonvulsant activity. The structural confirmation of the title compounds was achieved by spectral and analytical data. The anticonvulsant activity profile of synthesized compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) seizure tests, whereas their neurotoxicity was examined using rotarod test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. The majority of the compounds were effective in the MES or scMet screening tests. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. Most active compounds in the series were 3, 12 and 13, which bearing 2-methyl, 2-ethyl and 2-isopropyl substituent on the N-phenyl ring, respectively.

3-Anilinomethyl-5-chloro-1,3-­benzoxazol-2(3H)-one

In the title compound, C14H11ClN2O2, the 2,3-dihydro-1,3-benzoxazole ring system is essentially planar [maximum deviation = 0.009 (2) Å] and makes a dihedral angle of 79.15 (7)° with the phenyl ring. Intermolecular N—H⋯O and weak C—H⋯Cl hydrogen bonds occur in the crystal structure.

Synthesis, biological evaluation, and docking studies of some 5-chloro-2(3H)-benzoxazolone Mannich bases derivatives as cholinesterase inhibitors

A series of N‐substituted‐5‐chloro‐2(3H)‐benzoxazolone derivatives were synthesized and evaluated for their acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory, and antioxidant activities. The structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellmans colorimetric method. The free radical scavenging activity was also determined by in vitro ABTS (2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)) assay. The biological activity results revealed that all of the title compounds displayed higher AChE inhibitory activity than the reference compound, rivastigmine, and were selective for AChE. Among the tested compounds, compound 7 exhibited the highest inhibition against AChE (IC50 = 7.53 ± 0.17 μM), while compound 11 was found to be the most active compound against BuChE (IC50 = 17.50 ± 0.29 μM). The molecular docking study of compound 7 showed that this compound can interact with the catalytic active site (CAS) of AChE and also has potential metal chelating ability and a proper log P value. On the other hand, compound 2 bearing a methyl substituent at the ortho position on the phenyl ring showed better radical scavenging activity (IC50 = 1.04 ± 0.04 mM) than Trolox (IC50 = 1.50 ± 0.05 mM).

Crystal Structure and Theoretical Study of N,N-di[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazole-3-yl)methyl]ethanamine

The aim of the present work is to explore crystal and electronic structure of N,N-di[(5-chloro-2-oxo-2,3-dihydrobenzo[d]oxazole-3-yl)methyl]ethanamine. In the title compound, C18H15Cl2N3O4, the two 2, 3-dihydro-1, 3-benzoxazole ring systems are almost planar and make a dihedral angle of 96.12(7) with each other. The ethyl group is disordered over two set of sites with a site-occupancy ratio of 0.766(12):0.234(12). The crystal structure contain intermolecular C—H...O hydrogen bonds which form a zigzag chains along the c-axis, C—H...π interactions and π-π stacking interactions [centroid-centroid distance = 3.5668(19) A].

Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman’s colorimetric method. The biological activity results revealed that all of the title compounds (except for compound 8) displayed high selectivity against AChE. Among the tested compounds, compound 7 was found to be the most potent against AChE (IC50= 1.35 ± 0.08 μM), while compound 3 exhibited the highest inhibition against BuChE (IC50= 13.41 ± 0.62 μM). Molecular docking studies of the most active compound 7 in AChE showed that this compound can interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.

Synthesis and anticonvulsant activity of some N-(benzoyl)glycinanilide derivatives

Glycine is a major inhibitory neurotransmitter and recent studies have shown that certain lipophilic glycine derivatives demonstrate anticonvulsant activity in animal epilepsy models. On the other hand, anilide is another fruitful structure for designing potential anticonvulsant agents. Ameltolide, ralitoline and some phthalimide derivatives are the examples of anilide analogs with potent anticonvulsant activity. In this study, two key structural pharmacophores were combined and a series of N-benzoylglycinanilide derivatives were designed. Their anticonvulsant activities evaluated against maximal electroshock (MES) and subcutaneous metrazole seizure tests, whereas their neurotoxicity was examined by rotarod test. The preliminary screening results indicated that majority of the compounds were effective in the MES test. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. The most active compound in the series is N-(2-((4-methoxyphenyl)amino)-2-oxoethyl)benzamide (compound 8) which bearing 4-methoxy substituent on the N-phenyl ring.