harman and pyrimidine

A combined physicochemical and 3D technique is used to establish the QSAR of four series of non-benzodiazepines towards BzR. In physicochemical QSAR study, the semi-empirical PM3 based parameters like hardness, electronegativity, electrophilicity index, molar refractivity, heat of formation, solvent assessable surface area and logP were used as descriptors. The heat of formation (HF) and logP are recognized as the most important descriptors for binding affinity of such compounds to BzR. The 3D QSAR study reveals that beta-Carbolines of series "A" and Imidazo[1, 2-alpha]pyrimidines of series "C" show steric bulk interaction, the beta-Carbolines of series "B" and di-substituted purines of series "D" have dominance of electrostatic interaction with BzR. The CoMSIA also indicate the same trend in terms of steric and electrostatic interaction. The CoMSIA reveals that only in case of series "D", the hydrophobic field effect is important. Some possible candidates for all four series were designed and their probable activities were estimated by using different QSAR models. The activities of designed molecules are in better range and developed models might be helpful to design the potent ligands of BzR.

Topics: Benzodiazepines; Carbolines; Imaging, Three-Dimensional; Imidazoles; Inhibitory Concentration 50; Models, Molecular; Molecular Structure; Pyrimidines; Quantitative Structure-Activity Relationship; Software

FTIR, UV-vis, steady state and time-resolved fluorescence measurements show that harmane (1-methyl-9H-pyrido/3,4-b/indole) interacts with pyrimidine and its isomers pyrazine and pyridazine in its ground and lowest singlet states. The mechanisms of interaction are dependent on both the structure of the diazine and the nature of the solvent. Thus, in a low polar solvent such as toluene, harmane forms ground state 1:1 hydrogen-bonded complexes with all the diazines. These complexes quench the fluorescence of harmane and diminish its fluorescence lifetime. Conversely, in buffered (pH 8.7) aqueous solutions, pyrimidine behaves differently from the other diazines. Thus, whereas pyrimidine only interacts with harmane in its ground state, pyrazine and pyridazine also interact in the excited state. The harmane-pyrimidine ground state interaction is an entropic controlled process. Therefore, we propose the formation of pi-pi stacked 1:1 complexes between these substrates. Association constants for the different types of complexes and quenching parameters are reported.

Topics: Harmine; Kinetics; Models, Chemical; Pyrimidines; Spectrometry, Fluorescence; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Time Factors