Sedat Cosgun

Carbonic anhydrase inhibitors: Design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulfonamide derivatives.

The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315μM for hCA I and of 18.31-143.8μM against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitrophenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.

Differences between β-Ala and Gly-Gly in the design of amino acids-based hydrogels

Summary Despite the continuous interest in organogels and hydrogels of low molecular weight gelators (LMWG), establishing the relationship between the molecular structure and the gelation mechanism is still a challenge. In this paper our interest focuses on the consequences of slight molecular modifications on the self-assembling behaviour of β-Ala vs Gly-Gly-based hydrogelators. Previously, in our group, amino acid based amphiphiles i.e. Gly-Gly-His-EO2-Alk, a trimodular amphiphile (containing three domains: H-bond donor and acceptor/hydrophilic/hydrophobic domain, respectively) were reported to act as hydrogelators and that the gelation properties were related to hydrogen bonding, hydrophobic interactions and π-π stacking. Herein, β-Ala-His-EO2-Alk was fully characterised by FT-IR, NMR, SAXS and SEM and the gelation mechanism is discussed. It appears that the number of amide groups determines the self-assembling behaviour into 1D or 2D/3D networks as a result of intimate interactions between gelator molecules.

Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition.

Abstract The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with some 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives, were investigated by using the esterase assay, with 4-nitrophenyl acetate (4-NPA) as substrate. Compounds 10–13 showed KI values in the range of 112.7–441.5 μM for hCA I and of 3.5–10.76 μM against hCA II, respectively. These hydroxyl group containing compounds generally were competitive inhibitors. Some hydroxyl group containing compounds investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.

Genotoxicity potentials of anionic and cationic amino acid-based surfactants

To understand the genotoxic consequences of chemical agents, random amplification of polymorphic DNA (RAPD) as a useful biomarker to be used as an investigation tool for environmental toxicology. In this study, sodium dodecyl sulfate (SDS) was used as a toxic anionic surfactant, and glutamic acid-based cationic bicatanar surfactant (GS) was used as less toxic cationic amino acid-based surfactant. Experimental results show significant correlations between the RAPD profile changes with root growth, mitotic activity and chromosomal aberration test. The inhibitory rates of root growth at 400 ppm of SDS and GS were 85% and 32%, respectively. Mitotic activity results showed a drastic decrease in SDS exposures, whereas there was no significant decrease in GS treatment. Comparison of the chromosomal aberration test results, rates were indicated at 100, 200 and 400 ppm of SDS and GS; 10, 17, 26 (SDS) and 6, 9, 9 (GS) consequently. Also DNA alterations started at 100 and 200 ppm during SDS and GS exposures, respectively. These preliminary findings encourage the utilization of GS as an environmental friendly surfactant detected by these tools in the investigation of genotoxicity potentials of SDS and GS on maize and the other crops.