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Comparative Molecular Field Analysis (comparative + molecular_field_analysis)
Selected AbstractsCorrelation between the predicted and the observed biological activity of the symmetric and nonsymmetric cyclic urea derivatives used as HIV-1 protease inhibitors.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2003A 3D-QSAR-CoMFA method for new antiviral drug design Abstract The predicted inhibition constant (Ki) and the predicted inhibitor concentration (IC90) of the HIV-1 protease (HIV-1 PR) inhibitors: symmetric and nonsymmetric - benzyl, ketone, oxime, pyrazole, imidazole, and triazole cyclic urea derivatives, were obtained by the 3D-CoMFA (Comparative Molecular Field Analysis) method. The CoMFA statistical parameters: cross-validate correlation coefficient (q2), higher than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated the predicted biological activities. The best predictions were found for the trifluoromethyl ketoxime derivative (log 1/Ki predict = 8.42), the m-pyridineCH2 pyrazole derivative (log 1/Ki predict = 9.77) and the 1,2,3 triazole derivative (log 1/Ki predict = 7.03). We attempted to design a new potent HIV-1 protease inhibitor by addition of o-benzyl to the (p-HOPhCH2) pyrazole 12f derivative inhibitor. A favorable steric area surrounded the o-benzyl, suggesting a possible new potent HIV-1 protease inhibitor. [source] Bond-based 3D-chiral linear indices: Theory and QSAR applications to central chirality codificationJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2008Juan A. Castillo-Garit Abstract The recently introduced non-stochastic and stochastic bond-based linear indices are been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. These improved modified descriptors are applied to several well-known data sets to validate each one of them. Particularly, Cramer's steroid data set has become a benchmark for the assessment of novel quantitative structure activity relationship methods. This data set has been used by several researchers using 3D-QSAR approaches such as Comparative Molecular Field Analysis, Molecular Quantum Similarity Measures, Comparative Molecular Moment Analysis, E-state, Mapping Property Distributions of Molecular Surfaces, and so on. For that reason, it is selected by us for the sake of comparability. In addition, to evaluate the effectiveness of this novel approach in drug design we model the angiotensin-converting enzyme inhibitory activity of perindoprilate's ,-stereoisomers combinatorial library, as well as codify information related to a pharmacological property highly dependent on the molecular symmetry of a set of seven pairs of chiral N -alkylated 3-(3-hydroxyphenyl)-piperidines that bind ,-receptors. The validation of this method is achieved by comparison with earlier publications applied to the same data sets. The non-stochastic and stochastic bond-based 3D-chiral linear indices appear to provide a very interesting alternative to other more common 3D-QSAR descriptors. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] A 3-D QSAR Study of Catechol- O -Methyltransferase Inhibitors Using CoMFA and CoMSIAMOLECULAR INFORMATICS, Issue 10 2008Chunzhi Ai Abstract Inhibitors of Catechol- O -Methyltransferase (COMT) play an important role in the treatment of Parkinson's Disease (PD). A new Three-Dimensional Quantitative Structure,Activity Relationship (3-D QSAR) analysis was performed on 36 previously reported COMT inhibitors employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methodologies to correlate the molecular fields and percent inhibition values and three predictive models were derived. The CoMFA and CoMSIA models with steric and electrostatic field yielded cross-validated rs of 0.585 and 0.528, respectively whereas the conventional rs were 0.979 and 0.891, respectively. The CoMSIA model with hydrophobic field exhibited a r of 0.544 and a r of 0.930. The individual inspection of 3-D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. These 3-D QSAR models are also useful for designing and predicting novel COMT inhibitors. [source] Computer-aided design of selective COX-2 inhibitors: comparative molecular field analysis and docking studies of some 3,4-diaryloxazolone derivativesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 7 2001G. R. Desiraju Abstract The recent discovery of a second, inducible isoform of cyclooxygenase, COX-2, has stimulated the search for highly selective non-steroidal anti-inflammatory drugs (NSAIDs). These NSAIDs have the ability to treat pain and inflammation caused by arthritis with less risk of gastrointestinal or renal toxicity. We report here the results of 3D-quantitative structure,activity relationship and docking studies, performed on a series of 3,4-diaryloxazolones. Comparative moleculer field analysis studies provided a good model with cross-validated and conventional r2 values of 0.688 and 0.969 respectively for 24 analogues in the training set with six components. Docking studies with both COX-1 and COX-2 indicate good selectivity for COX-2. The binding energies between COX-2 and some of the most active oxazolones are comparable to those of celecoxib or rofecoxib. These compounds adopt similar orientations and form similar sets of hydrogen bonds involving the sulfonyl group of the ligand and His 90, Leu 352, Ser 353, Arg 513, Phe 518 and Ser 530 residues of the receptor. Copyright © 2001 John Wiley & Sons, Ltd. [source] 3D-QSAR Studies on C24-Monoalkylated Vitamin D3 26,23-Lactones and their C2, -Modified Derivatives with Inhibitory Activity to Vitamin D ReceptorMOLECULAR INFORMATICS, Issue 8-9 2010Jinhu Wang Abstract The ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) for 82 inhibitors of 25-dehydro-1, -hydroxyvitamin D3 -26,23-lactone analogs has been studied by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The established CoMFA model in training set gives a cross-validated q2 value of 0.516 and a non-cross-validated rncv2 value of 0.667, while the CoMSIA model results in q2=0.517 and rncv2=0.632. In general, the predictive ability of the CoMFA model is superior to that of the CoMSIA model, with rpred2=0.639 for the CoMFA and rpred2=0.619 for the CoMSIA model. Based on the CoMFA contour maps, some key structural characters of vitamin D3 analogs responsible for inhibitory activity are identified, and some new C2, -modified 24-alkylvitamin D3 lactone analogs with high predicted pIC50 values are designed. The ligand functional group mutations by FEP simulation and docking studies reveal the rationality of the molecular design. [source] Synthesis, Herbicidal Activities and Comparative Molecular Field Analysis Study of Some Novel Triazolinone DerivativesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2009Lei Wang A series of novel triazolinones were synthesized and their structures were characterized by 1H NMR, elemental analysis and single-crystal X-ray diffraction analysis. The herbicidal activities were evaluated against Echinochloa crusgalli (L.) Beauv., Digitaria adscendens, Brassica napus and Amaranthus retroflexus. The herbicidal activity data indicated that the title compounds had higher activities with substituted benzyl group moieties than with other groups such as sulfonyl, alkyl, etc. To further investigate the structure,activity relationship, comparative molecular field analysis was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of comparative molecular field analysis are in good agreement in this work. The results showed that a bulky and electronegative group around the ortho- or para -positions of the benzene ring would possibly lead to higher activity. Based on the comparative molecular field analysis, compound I-23 was designed and synthesized, which display as good herbicidal activities as the commercial herbicide, carfentrazone-ethyl. The activity against Digitaria adscendens is 66.1% under pre-emergence at 300 g of a.i./ha. [source] | ||||||||||