NOPR Collection:

A quantitative and a qualitative study of the resonance assisted double proton transfer in formic acid dimer

Sun, 01 Jan 2006 00:00:00 GMT

Title: A quantitative and a qualitative study of the resonance assisted double proton transfer in formic acid dimer Authors: Shettya, Sharan; Pal, Sourav; Kanhere, Dilip G; Goursot, Annick Abstract: Ab initio molecular dynamics simulations have been performed to study the nature of the synchronous double proton transfer in formic acid dimer. In order to understand the evolution of the bonding during the double proton transfer, the electron localization function and the molecular orbital isosurfaces have been used. During the dynamics of the double proton transfer in formic acid dimer the two formic acid monomers approach each other, forming Speakman-Hadzi type of short strong hydrogen bonds at the transition state. The Speakman-Hadzi type of short strong hydrogen bonds are also shown to be polar covalent bonds. Based on the concept of resonance assisted hydrogen bond proposed by Gilli et al (Gilli P, Bertolasi V, Ferretti V & G. Gilli, J Am Chem Soc, 116 (1994) 909), it is shown that the proton at the transition state is connected by a π-conjugated O — C — O structures, indicating a resonance assisted hydrogen bond. On this basis the double proton transfer process in the formic acid dimer can be termed as a resonance assisted double proton transfer. The present work indicates that the synchronous double proton transfer in the formic acid dimer is due to the formation of (a) Speakman Hadzi type of short strong hydrogen bonds, and (b) resonance assisted hydrogen bond at the transition state. Page(s): 202-212

Comparative 2D and 3D-QSAR of antifungal griseofulvin analogues

Sun, 01 Jan 2006 00:00:00 GMT

Title: Comparative 2D and 3D-QSAR of antifungal griseofulvin analogues Authors: Juvale, Dhanshri C; Kadam, Shivajirao S; Kulkarni, Vithal M Abstract: A series of griseofulvin analogues has been examined to determine the structural requirements of antifungal activity by three-dimensional quantitative structure-activity relationship studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA ) methods. Evaluation of 22 compounds (training set) has established the CoMFA and CoMSIA models, which have been validated by evaluation of a set of four compounds (test set). The lowest energy conformer of the most active molecule obtained from systematic search has been used as the template structure for the alignment. In this study, the superimposition of molecules was carried out by atom-based fit (rms), multi fit and field fit. Along with steric and electronic fields, ClogP has been taken as additional descriptor to account for lipophilicity. Further, a QSAR analysis has been carried out using Tools for Structure-Activity Relationship software. For this study, various chemical descriptors such as electronic, steric, lipophilic, topological have been calculated and multiple regression carried out. The QSAR models from these three methods exhibit considerable correlative and predictive properties. The models obtained from the present study may be useful for the development of new griseofulvin analogues as potential antifungals. Page(s): 194-201

Molecular docking studies on pyridine derivatives of glitazones as PPARγ agonists

Sun, 01 Jan 2006 00:00:00 GMT

Title: Molecular docking studies on pyridine derivatives of glitazones as PPARγ agonists Authors: Bharatam, Prasad V; Khanna, Smriti Abstract: FlexX software has been employed to perform molecular docking analysis on a series of glitazones in the active site of PPARγ. FlexX scores and interaction energies of glitazones have been compared with those of the corresponding pyridine analogs. The results point out that the binding affinities do not significantly change due to the benzene versus pyridine substitution in the central ring of PPARγ. The experimentally observed differences do not originate from the differences in the binding affinities. Page(s): 188-193

Functional correlation of cyclooxygenases-l, 2 and 3 from amino acid sequences and three dimensional model structures

Sun, 01 Jan 2006 00:00:00 GMT

Title: Functional correlation of cyclooxygenases-l, 2 and 3 from amino acid sequences and three dimensional model structures Authors: Nagini, M; Reddy, G V; Hemalatha, G R; Guruprasad, Lalitha; Reddanna, P Abstract: COX-1, COX-2 and COX-3, three isoforms of cyclooxygenase are differentially expressed . We have analyzed the sequences of these cyclooxygenases and built the three dimensional model structures for human COX-1, COX-2 and canine COX-3 to characterize the function of cyclooxygenase isozymes based on the sequence and structure information. Sequence analysis reveals that COX-3 shares 90% homology with COX-1 and 60% with COX-2. The COX-1 model has been compared with those of COX-2 and COX-3 and the active site regions have been analyzed. The major differences in the active sites of COX-1 and COX-2 are: Ile 523 in COX-1 is replaced by Val in COX-2, apart from a few mutations at the mouth of the active site. No such differences in the active sites are seen between COX-1 and COX-3 structures and the amino acid residues that differ between COX-1 and COX-3 lie only on the surface of the protein. Therefore, it is hard to explain the specificity of acetaminophen towards COX-3. Further, the nitron 1 of canine COX-1 gene that is retained in COX-3 mRNA transcript codes for a poly proline region that could be responsible for intermolecular interactions. Page(s): 182-187