ABSTRACT
The study of modified synthetic procedure of water soluble morin-5'-sulfonic acid sodium salt (NaMSA) involving less aggressive chemicals and carried out at mild conditions was described. The NaMSA salt is a convenient source of anionic morin-5'-sulfonic ligand (MSA) in ion exchange reactions. The coordination ability of MSA ligand towards the zinc cations was investigated in aqueous solution and in solid state. Novel zinc complexes of morin-5'-sulfonate were obtained by a reaction of Zn(NO3)2 with morin-5'-sulfonate in water. Resulting compounds were characterized by single-crystal X-ray diffraction analysis, as well as spectral and thermal methods. The coordination interaction, hydrogen bond and π-π stacking lead to the formation of a 1D chain or 3D coordination polymers. The antioxidant activity of the Zn(II)-MSA complexes was evaluated by means of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. In this work, we have shown that the studied compounds are more effective free radical scavengers than the natural flavonoids like plain morin.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antioxidants/chemical synthesis , Coordination Complexes/chemical synthesis , Flavonoids/chemistry , Malonates/chemistry , Organoplatinum Compounds/chemical synthesis , Sulfonic Acids/chemistry , Zinc/chemistry , Animals , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/pharmacology , Coordination Complexes/pharmacology , Crystallography, X-Ray , Female , Humans , Inhibitory Concentration 50 , Male , Mice , NIH 3T3 Cells , Organoplatinum Compounds/pharmacology , Pyrimidines/chemistry , Structure-Activity RelationshipABSTRACT
Derivatives of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine were synthesized. These compounds contain the 3-(4-piperidyl)-1H-indole residue or its 5-methoxy or 2-methyl derivative. In vitro binding tests were performed to determine the affinity of the compounds for the 5-HT(1A) receptor and serotonin transporter (SERT) proteins in the rat brain cortex. In vivo studies, particularly the inducible hypothermia test and forced swimming test, were conducted to determine agonistic/antagonistic activity with pre- and postsynaptic 5-HT(1A) receptors. Molecular modeling techniques were used to determine the binding modes of the selected compounds at the 5-HT(1A) receptor and SERT. The SAR analysis showed that the presence of the 3-(4-piperidyl)-1H-indole group or its 5-methoxy derivative, as well as a para substitution with -OCH(3) or -F in the aryl ring of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine, results in an increased affinity for both the 5-HT(1A) receptors and SERT. In contrast, the presence of the 2-methyl-3-(4-piperidyl)-1H-indole group resulted in a considerable decrease in binding affinity.
