Emine Elçin Oruç-Emre

Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities

Abstract A series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UV–Vis, IR, 1H NMR, 13C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners.

Biting deterrence and insecticidal activity of hydrazide-hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles against Aedes aegypti.

BACKGROUND Taking into account the improvement in insecticidal activity by the inclusion of fluorine in the hydrazone moiety, the authors synthesized new 4-fluorobenzoic acid hydrazides and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles, substituting a phenyl group or a heteroaryl ring carrying one or two atoms of F, Cl and Br, and investigated their biting deterrent and larvicidal activities against Aedes aegypti for the first time. RESULTS The compound 3-acetyl-5-(4-fluorophenyl)-2-[4-(dimethylamino)phenyl]-2,3-dihydro-1,3,4-oxadiazole (17) produced the highest biting deterrent activity (BDI = 1.025) against Ae. Aegypti, followed by 4-fluorobenzoic acid [(phenyl)methylene] hydrazide (1). These activity results were similar to those of N,N-diethyl-meta-toluamide (DEET), which showed a proportion not biting of 0.8-0.92. When compounds 1 and 17 were tested on cloth worn on human volunteers, compound 1 was not repellent for some volunteers until present in excess of 500 nmol cm(-2) , while compound 17 was not repellent at the highest concentration tested (1685 nmol cm(-2) ). In the larvicidal screening bioassays, only compounds 10, 11, 12 and 17 showed 100% mortality at the highest screening dose of 100 ppm against Ae. aegypti larvae. Compounds 11 and 12 with LD50 values of 24.1 and 30.9 ppm showed significantly higher mortality than 10 (80.3 ppm) and 17 (58.7 ppm) at 24-h post-treatment. CONCLUSION The insecticidal and biting deterrent activities were correlated with the presence of a halogen atom on the phenyl or heteroaryl substituent of the hydrazone moiety.

Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents.

Microwave-assisted synthesis of new sulfonyl hydrazones, screening of biological activities and investigation of structure–activity relationship

Sulfonyl hydrazone scaffold and the piperidine rings have important role in medicinal chemistry. This study shows the synthesis of two novel series of sulfonyl hydrazone having piperidine derivatives by condensing benzene sulfonyl hydrazides with ethyl 4-oxopiperidine-1-carboxylate and 2,6-diphenylpiperidin-4-one. Physical and chemical properties of compounds have been characterized and reported by utilizing their melting point, elemental analysis, IR, 1H-NMR, 13C NMR, 2D NMR and mass spectra results. Synthesized compounds were evaluated for antioxidant capacity and anticholinesterase activity. The antioxidant capacity of the compounds were screened through four complementary test, i.e., β-carotene–linoleic acid for lipid peroxidation, DPPH free radical (DPPH·), ABTS cation radical (ABTS+·) and CUPRAC assays. Assay results showed that N′-(2,6-diphenylpiperidin-4-ylidene)-4-bromobenzenesulfonohydrazide (11) has the highest lipid peroxidation inhibitory activity. Within the assay series, N′-(2,6-diphenylpiperidin-4-ylidene)-4-bromobenzenesulfonohydrazide (11) exhibited better activity than standard BHT in DPPH· scavenging, while N′-(2,6-diphenylpiperidin-4-ylidene)benzenesulfonohydrazide (10) showed the best ABTS+· scavenging assay. The CUPRAC assay revealed that ethyl 4-(2-(4-methoxyphenylsulfonyl)hydrazono)piperidine-1-carboxylate (5) indicated the best activity with A0.50 value among the tested compounds than the antioxidant standard α-tocopherol. According to AChE assay, N′-(2,6-diphenylpiperidin-4-ylidene)-4-chlorobenzenesulfonohydrazide (12) had the best activity, while in BChE assay the highest activity was found for compound N′-(2,6-diphenylpiperidin-4-ylidene)-4-methylbenzenesulfonohydrazide (16). Electronic and structural characteristics and density functional studies of the all newly synthesized compounds have been reported for better understanding in molecular-level. NMR, molecular electrostatic potential (MEP), ΔEHOMO–LUMO band gap and the dipole moments of the molecules have been also analyzed and reported.Graphical Abstract

Synthesis, Characterization, and Biological Evaluation of Some Novel Thiosemicarbazones as Possible Antibacterial and Antioxidant Agents

Abstract The synthesis and characterization of 18 novel thiosemicarbazones have been investigated as part of a research program on development of compounds with antibacterial and antioxidant activities. Among the tested compounds, 2-(4-hydroxybenzylidene)-N-[4-(trifluoromethoxy)phenyl]hydrazine carbothioamide (3g) and 2-(thiophen-2-ylmethylidene)-N-[4-(morpholin-4-yl)phenyl]hydrazine carbothioamide (4b) showed excellent inhibition potency at low concentration (0.5 μg/mL) against Gram-positive pathogens (Enterococcus faecalis and Staphylococcus aureus). All tested compounds were also found to possess antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation. [Supplementary materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, tables, and figures.] GRAPHICAL ABSTRACT

X-ray structures and spectroscopic properties of chiral thiosemicarbazides as studied by computational calculations

GRAPHICAL ABSTRACT ABSTRACT In the present work, (+)-(R)-1-[2-(benzenesulfonamido)-3-phenylpropanoyl]-4-[(4-methoxy)phenyl]thiose micarbazide (1a) and (−)-(S)-1-[2-(benzenesulfonamido)-3-phenylpropanoyl]-4-[(4-methoxy)phenyl] thiosemicarbazide (1b) were synthesized starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The single crystal structures were characterized by XRD, FTIR and 1H and 13C NMR spectroscopy. Density functional theory (DFT) calculations (B3LYP/6-311G(d,p) were carried out to obtain the ground state optimized geometry, the IR and the NMR spectra of the molecule. Electronic properties (HOMO&LUMO) were calculated using the Time Dependant-DFT/B3LYP/6-311G(d,p) method. Furthermore, NBO, MEP, and Fukui function analyses have been used for the quantitative determination of the chemical activities at various sites of the molecule.

Synthesis, characterization, spectroscopy, X-ray structure and gaussian hybrid computational investigation of (−)-(S)-1-[2-(benzenesulfonamido)-3-phenylpropanoyl]-4-[(4-methyl)phenyl]thiosemicarbazide

Abstract The molecule (−)-(S)-1-[2-(benzenesulfonamido)-3-phenylpropanoyl]-4-[(4-methyl)phenyl] thiosemicarbazide was synthesized and its structure analyzed by X-ray diffraction to understand its geometry, and inter/intra-molecular interactions. Theoretical calculations were carried out using DFT and TD-DFT methods with B3LYP/6-31G(d, p) and B3LYP/6-31G + (d, p) basis sets. Theoretical bond parameters, harmonic vibration frequencies, and chemical shifts are in good agreement with the experimental results. Electronic properties of the molecule derived from frontier orbitals, molecular electrostatic potential, and theoretical UV-Visible spectrum are validated experimentally. Graphical Abstract

Design and evaluation of biological activities of 1,3-oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties

1,3‐Oxazolidine‐2‐one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1–22) were obtained by the reaction of (S)‐4‐(4‐aminobenzyl)‐2(1H)‐1,3‐oxazolidinone with 4‐substituted benzoyl chlorides, 4‐substituted benzene sulfonyl chlorides, and 4‐substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT‐IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram‐positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non‐mutagenic and non‐cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16.