Hasan Türkmen

Comparative QSTR Study Using Semi-Empirical and First Principle Methods Based Descriptors for Acute Toxicity of Diverse Organic Compounds to the Fathead Minnow

Several quantum-mechanics-based descriptors were derived for a diverse set of 48 organic compounds using AM1, PM3, HF/6-31+G, and DFT-B3LYP/6-31+G (d) level of the theory. LC50 values of acute toxicity of the compounds were correlated to the fathead minnow and predicted using calculated descriptors by employing Comprehensive Descriptors for Structural and Statistical Analysis (CODESSA) program. The heuristic method, implemented in the CODESSA program for selecting the ‘best’ regression model, was applied to a pre-selection of the most-representative descriptors by sequentially eliminating descriptors that did not satisfy a certain level of statistical criterion. First model, statistically, the most significant one has been drawn up with the help of DFT calculations in which the squared correlation coefficient R2 is 0.85, and the squared cross-validation correlation coefficient RCV2 is 0.79. Second model, which has been drawn up with the help of HF calculations, has its statistical quality very close to the DFT-based one and in this model value of R2 is 0.84 and that of RCV2 is 0.78. Third and fourth models have been drawn up with the help of AM1 and PM3 calculations, respectively. The values of R2 and RCV2 in the third case are correspondingly 0.79 and 0.66, whereas in the fourth case they are 0.78 and 0.65 respectively. Results of this study clearly demonstrate that for the calculations of descriptors in modeling of acute toxicity of organic compounds to the fathead minnow, first principal methods are much more useful than semi-empirical methods.

Synthesis of Schiff base derivatives of 4-(2-aminoethyl)-benzenesulfonamide with inhibitory activity against carbonic anhydrase isoforms I, II, IX and XII

Schiff base derivatives were obtained by reaction of 4-(2-aminoethyl)benzenesulfonamide with aromatic aldehydes. The corresponding secondary amine derivatives were also prepared by reduction of the imine compounds with NaBH4. These derivatives were investigated as inhibitors of four human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic isozymes hCA I and II, as well as, the transmembrane, tumor-associated hCA IX and XII. Some of the newly synthesised compounds showed effective inhibitory activities against these CA isozymes. Many low nanomolar inhibitors were detected against all isoforms among the secondary amines whereas the Schiff bases were by far less active compared to the corresponding reduced derivatives among all investigated isoforms.

Synthesis of sulfanilamide derivatives and investigation of in vitro inhibitory activities and antimicrobial and physical properties

Novel sulfanilamide derivatives were synthesized and evaluated for carbonic anhydrase inhibitory activity as a target for the treatment of glaucoma, and antibacterial properties for use in chemotherapy. Synthesized compounds were characterized by FT-IR, (1)H NMR, (13)C NMR and photoluminescence. In vitro inhibitory activities were measured by UV-Vis and some of the compounds were found have greater inhibitory effects than the lead compound sulfanilamide. The correlation between inhibitory activity, biological properties and the physicochemical properties of water solubility and partition coefficients was also investigated. Sulfanilamide derivatives gave intense emissions upon irradiation by UV light and a dimethyl substituted compound and a cyclic analog have photoluminescence quantum yields 42% and 31% and long excited-state lifetimes of 3.92 and 2.91 ns, respectively.

Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII.

Imine derivatives were obtained by condensation of sulfanilamide with substituted aromatic aldehydes. The Schiff bases were thereafter reduced with sodium borohydride, leading to the corresponding amines, derivatives of 4-sulfamoylphenyl-benzylamine. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). We noted that the compounds incorporating secondary amine moieties showed a better inhibitory activity against all CA isozymes compared to the corresponding Schiff bases. Low nanomolar CA II, IX and XII inhibitors were detected, whereas the activity against hCA I was less potent. The secondary amines incorporating sulfonamide or similar zinc-binding groups, poorly investigated chemotypes for designing metalloenzyme inhibitors, may offer interesting opportunities in the field due to the facile preparation and possibility to explore a vast chemical space.

3-Chloro-N-(4-sulfamoylphen­yl)propanamide

In the title compound, C9H11ClN2O3S, the dihedral angle between the benzene ring and the amido –NHCO– plane is 15.0 (2)°. An intramolecular C—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal structure, the amino NH2 group is involved in intermolecular N—H⋯O hydrogen bonds, which connect the molecules into a double layer structure expanding parallel to the bc plane. The layers are further linked by an amido N—H⋯O hydrogen bond. Between the layers, a weak π–π interaction with a centroid–centroid distance of 3.7447 (12) Å is also observed.

2-Chloro-N-(4-sulfamoylphen­yl)acetamide

In the title compound, C8H9ClN2O3S, the benzene ring makes a dihedral angle of 4.1 (9)° with the amido –NHCO– plane including the major occupancy component of the carbonyl O atom [19 (4)° for the minor component]. An intramolecular C—H⋯O interaction occurs. The O atom of the carbonyl group is disordered over two positions with site-occupancy factors of 0.67 (11) and 0.33 (11). Intermolecular N—H⋯O hydrogen bonds help to stabilize the crystal structure.

Synthesis, characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide)benzenesulfonamide derivatives

In this study, several sulfonamide derivatives, 4-(2-methylacetylamino)benzenesulfonamides were synthesized. Chemical structures of the derivatives were characterized by 1H NMR, 13C NMR, LC-MS-MS, UV-Vis, FTIR, photoluminescence and elemental analysis. Sulfanilamide was reacted with 2-bromopropionyl bromide, in the presence of pyridine, to form bromo-substituted sulfonamide key intermediates, which were subsequently treated with secondary amines to obtain novel sulfonamide derivatives. All the synthesized compounds were evaluated for in vitro antimicrobial activities and cytotoxicity. Increases in ring size, and rings bearing a nitrogen heteroatom led to improvements in antimicrobial activities. As the presence of CA IX and CA XII enzymes have been implicated in some cancerous tumors, the studies presented herein focuses on targeting these enzymes. It was found that the synthesized derivatives had in vitro anti-cancer properties, where compounds (3-6) were found to be active against all cancerous cells, and no cytotoxic effects on normal cells were observed.

4-(3-Chloro-2,2-dimethyl-propanamido)-benzene-sulfonamide.

In the title compound, C11H15ClN2O3S, the 3-chloro-2,2-dimethylpropanamide and sulfonamide substituents are arranged on opposite sides of the benzene ring plane. In the crystal, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network.

4-{[4-(Di­methyl­amino)­benzyl­idene]amino}­benzene­sulfonamide

The title Schiff base compound, C15H17N3O2S, is non-planar with a dihedral angle of 69.88 (4)° between the planes of the benzene rings. In the crystal, pairs of N—H⋯N hydrogen bonds, between the sulfonamide nitrogen-H atom and the azomethine N atom, link the molecules into inversion dimers, forming R 2 2(16) ring motifs. These dimers are linked by N—H⋯O hydrogen bonds, between the sulfonamide nitrogen-H atom and one sulfonamide O atom, forming sheets lying parallel to (100). Within the sheets there are weak parallel slipped π–π interactions involving inversion-related benzenesulfonamide rings [centroid–centroid distance = 3.8800 (9) Å; normal distance = 3.4796 (6) Å; slippage = 1.717 Å].

4-(5-Chloro­penta­namido)­benzene­sulfonamide

The molecular conformation of the title compound, C11H15ClN2O3S, is stabilized by a C—H⋯O hydrogen bond, forming an S(6) ring motif. In the crystal, molecules are linked by two pairs of inversion-related N—H⋯O hydrogen bonds, generating R 2 2(8) and R 2 2(20) ring motifs, resulting in chains running along [0-11]. These chains are connected by N—H⋯O hydrogen bonds along [100], forming layers parallel to (011). There are also C—H⋯π interactions between the layers, which consolidate the three-dimensional structure.