Mustafa Emirik

Synthesis and molecular docking study of some 5,6-dichloro-2-cyclopropyl-1H-benzimidazole derivatives bearing triazole, oxadiazole, and imine functionalities as potent inhibitors of urease

A new series of benzimidazole compounds including hydrazinecarbothioamide, 1,2,4-triazole, 1,3,4-oxadiazole and imine function were synthesized starting from 5,6-dichloro-2-cyclopropyl-1H-benzimidazole. All of the benzimidazole derivatives exhibited good urease inhibitor activity. Compound 6a proved to be the most potent showing an enzyme inhibitory activity with an IC50=0.06µM. Molecular docking studies were also conducted on enzyme extracted from Jack bean urease to identify the binding mode of the newly synthesized compounds.

Spectroscopic, electrochemical, theoretical characterization and biological evaluation of a ferrocenyl-substituted unsymmetric azine ligand and its Cu(II) complex

Abstract Ferrocenyl-substituted unsymmetrical azine and its Cu(II) complex were prepared. The redox active ferrocene-based azine was obtained by condensation of 1-[(E)-hydrazono]-5-bromo-2-hydroxybenzene with ferrocene carboxaldehyde. The ferrocenyl ligand and its Cu(II) complex were characterized by IR, UV–vis, NMR, X-ray, magnetic susceptibility, molar electrical conductivity measurements, and TG techniques. The redox behaviors of the ferrocene compounds were investigated by cyclic voltammetry. Structural parameters and spectroscopic properties of the ligand and the Cu(II) complex were calculated by employing density functional theory (DFT) and time-dependent DFT and compared with available experimental data. We found slightly stronger binding ability for Cu(II) complex than the free ligand. DNA binding abilities for ferrocenyl-substituted unsymmetrical azine ligand and its Cu(II) complex are higher than some reported ferrocene compounds. We also studied DNA cleavage, superoxide and DPPH radical scavenging abilities of the compounds. Furthermore, the synthesized organometallic compounds can be bound to DNA through an intercalative mode.

A simple and efficient synthesis of novel inhibitors of alpha-glucosidase based on benzimidazole skeleton and molecular docking studies.

A novel series of benzimidazole derivatives were prepared starting from o-phenylenediamine and 4-nitro-o-phenylenediamine with iminoester hydrochlorides. Acidic proton in benzimidazole was exchanged with ethyl bromoacetate, then ethyl ester group was transformed into hydrazide group. Cyclization using CS2/KOH leads to the corresponding 1,3,4-oxadiazole derivative, which was treated with phenyl isothiocyanate resulted in carbothioamide group, respectively. As the target compounds, triazole derivative was obtained under basic condition and thiadiazole derivative was obtained under acidic condition from cyclization of carbothioamide group. Most reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. All compounds obtained in this study were investigated for α-glucosidase inhibitor activity. Compounds 6a, 8a, 4b, 5b, 6b and 7b were potent inhibitors with IC50 values ranging from 10.49 to 158.2μM. This has described a new class of α-glucosidase inhibitors. Molecular docking studies were done for all compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.

Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors

In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC50 values of 1.72 ± 0.12 µM, 1.92 ± 0.28 and 0.98 ± 0.07 µM, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms.

Synthesis and molecular docking study of some novel 2,3-disubstituted quinazolin-4(3H)-one derivatives as potent inhibitors of urease

A new series of 2,3-disubstituted quinazolin-4(3H)-one compounds including oxadiazole and furan rings was synthesized. Their inhibitory activities on urease were assessed in vitro. All newly synthesized compounds exhibited potent urease inhibitory activity in the range of IC50 = 1.55 ± 0.07-2.65 ± 0.08 µg/mL, when compared with the standard urease inhibitors such as thiourea (IC50 = 15.08 ± 0.71 µg/mL) and acetohydroxamic acid (IC50 = 21.05 ± 0.96 µg/mL). 2,3-Disubstituted quinazolin-4(3H)-one derivatives containing furan ring (3a-e) were found to be the most active inhibitors when compared with the compounds 2a-e bearing oxadiazole ring. Compound 3a, bearing 4-chloro group on phenyl ring, was found as the most effective inhibitor of urease with the IC50 value of 1.55 ± 0.11 µg/mL. The molecular docking studies of the newly synthesized compounds were performed to identify the probable binding modes in the active site of the Jack bean urease (JBU) enzymes.

A Novel Ferrocenyl Naphthoquinone Fused Crown Ether as a Multisensor for Water Determination in Acetonitrile and Selective Cation Binding

A multisensor which is based on a novel multifunctional triad molecule, ferrocenyl naphthoquinone fused crown ether (Fc-cnq) bearing ferrocene, quinone, and crown ether functional groups together, was synthesized and characterized in this study. Sensing performance of a trace amount of water and the selective cation binding capabilities of this multisensor were carried out by the electrochemical, spectroelectrochemical, and spectrophotometric titration techniques in acetonitrile (CH3CN). It was shown that the potential separation (E((Fc))1/2 - E((2))1/2) between the second reduction of naphthoquinone and the oxidation processes of ferrocene in the triad molecule Fc-cnq was proportional to the amount of water due to the hydrogen-bonding interactions between water and the doubly reduced species (Fc-cnq(2-)). This property enabled Fc-cnq to detect the trace amount of water in CH3CN. The half-wave potential (E((Fc))1/2) of the ferrocene in Fc-cnq was used as an internal reference potential, and it defined the accuracy of the detection. In addition, by using the UV-vis spectrophotometric titration technique in CH3CN, it was also shown that the Fc-cnq multisensor could bind Ba(2+) and Ca(2+) cations selectively. We proposed that the intramolecular charge-transfer (CT) transition which occurred between the donor ferrocene and the acceptor naphthoquinone was the principle mechanism for the selective binding property of this multisensor. Quantum chemical calculations were also performed to investigate optical and electronic properties of the Fc-cnq molecule.

Synthesis, invitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole, thiadiazole and thiosemicarbazide functionalities

A new series of quinazolinone derivatives containing triazole, thiadiazole, thiosemicarbazide functionalities was synthesized and then screened for their in vitro urease inhibition properties. Most of the compounds showed excellent activity with IC50 values ranging between 1.88 ± 0.17 and 6.42 ± 0.23 µg/mL, compared to that of thiourea (IC50 = 15.06 ± 0.68) and acetohydroxamic acid (IC50 = 21.03 ± 0.94), as reference inhibitors. Among the synthesized molecules, compounds 5c, 5e and 5a showed the best inhibitory effect against urease enzyme with IC50 values of 1.88 ± 0.17 µg/mL, 1.90 ± 0.10 and 1.96 ± 0.07 µg/mL, respectively. Moreover in order to give better understanding of the inhibitory activity of synthesized compounds, molecular docking studies were applied at the target sites of jack bean urease enzyme (JBU). Their binding poses and energy calculations were analyzed using induced fit docking (IFD) and prime-MMGBSA tool. Binding poses of studied compounds were determined using induced fit docking (IFD) algorithms.