|Analysis of in silico stereoelectronic properties of PMD (p-menthane-3-8-diols) and its derivatives to develop a pharmacophore for insect repellent activity |
Bhattacharjee AK, Chauhan K, Bathini N, Greico J, Achee N, Lawrence K, Benante JP and Gupta RK
PMD, an insect repellent that can be derived from steam distillate residue of leaves of lemon eucalyptus. No QSAR studies are known in literature. We performed ab initio (RHF/6-31G**) study of PMD derivatives. A 3D pharmacophore for repellent activity was also developed. Results indicate lipophilicity, MEP separation and localized negative MEP by oxygen atom have roles for repellency. The pharmacophore is consistent and allowed design of more effective insect repellents.
|DOCKING STUDIES OF A NEW HETEROCYCLIC METHYLTHIOMORPHOLIN PHENOLS DERIVATIVES AS ANTIHYPERTENSIVE DRUGS WITH ACE TARGET.CASE FESCDIPINE II |
1V. Vázquez,1O. Vázquez, 1,2M.A.Balboa, 1A. Ma. Velázquez, 1V.H. Abrego, 1B.Camacho, 1L. Martínez, 1L.A. Torres, 1A. Ramírez, 1I.Martínez, 3R.López-Castañares, 1S.Díaz-Barriga, 4J. Bocanegra, 4Froylan Gómez-Laguna, 1F. Olvera, 1E.Angeles.
As part of the Drug Design in Medicinal Chemistry Program of the UNAM, new methylthiomorpholinphenol compounds with cardiovascular effect, were studied. One of them, FESCDIPINE II, was an excellent antihypertensive drug, that has low toxicity and preliminary studies indicate that the Angiotensin-converting enzyme (ACE) system is the biological target of this compound.
|A Novel Design of Artificial Membrane for Improving the PAMPA Model|
Xiaoxi (Kevin) Chen, Ph.D., Anthony Murawski, Linda Hladik, and Charles L. Crespi, Ph.D.
The Parallel Artificial Membrane Permeability Assay (PAMPA) is a well-accepted screening assay for ADME properties (membrane permeability).
|Validation of Time-Dependent Cytochrome P450 Inhibition assays: Use of Stable - Labeled Isotope Internal Standards for Optimal Quantitation|
Elke S. Perloff, Andrew Mason, Shangara S. Dehal, Andrew P. Blanchard, Ling Morgan, Andre Dandeneau, Thuy Ho, Ronell M. Crocker, Catherine M. Chandler, Nathalie Boily, Charles L. Crespi, and David M. Stresser
Time-dependent inhibition of cytochrome P450 (CYP) metabolism can lead to nonlinear pharmacokinetics and drug-drug interactions. Recent guidance from the USFDA and drug failures attributable to toxicity that may have a basis in time-dependent inhibition, have elevated interest in this long-known undesirable property of drug candidates.
|Applications of Inside-Out Vesicle Uptake Assay to Assess the Inhibitory Effects of Various Drugs on Human MRP2 and Rat Mrp2 Transporters|
Vina Ketty, Eric Sands, Joanne Bourgea, Chris J. Patten, Charles L. Crespi, Ph.D., and Guangqing Xiao
Human MRP2 and rat Mrp2 inside-out vesicles were prepared from Spodoptera frugiperda (Sf9) insect cells expressing the corresponding transporters. MRP2 mediated and ATP dependent uptake of 3H-LTC4 was conducted using the rapid filtration system in the absence or presence of MgATP.
|Development of a High-Throughput Microarray for Evaluating CYP1A1 Induction|
Megan Mason, XinXin Ding, Jonathan S. Dordick
The aim of this study is to produce a vector capable of expressing green fluorescent protein (GFP) when exposed to a CYP1A1 inducer.
|A Walk-Up ADME Testing System for Medicinal Chemists and Pharmacologists|
Muhammad Alimuddina, Martin Peacock, Russell Dahl, Omar Jina, and Paul Oakley
VivADME was born with the fusion of a problem and a solution: recognition by a Medicinal Chemist that ADME data took too long to obtain, and, the realization that microfluidic tools could address the problem. The vivADME microfluidics solution means that ADME profiling can be performed in minutes with microgram-scale samples in a walk-up system with a very low cost per sample.
|Functional Evaluation of SLC Transporters in BD Gentest™ Cryopreserved Human Hepatocytes Using an Oil-Filtration Suspension Assay|
1Eric Sands, 1Vina Ketty, 2Yong-Hae-Han, 1Joanne Bourgea, 1Chris J. Patten, 1Charles L. Crespi, and 1Guangqing Xiao
The purpose of this study was to evaluate the function of Sodium Taurocholate Co-transporting Polypeptide (NTCP), Organic Anion Transporting Polypeptide (OATP), and Organic Cation Transporter (OCT) in cryopreserved human hepatocytes, and to examine the impact of various drugs on hepatic transporter-mediated uptake. Cryopreserved human hepatocytes were prepared using the Percoll™ method.
|Bioluminescent Approaches for In Vitro ADMET|
James J Cali, Mary Sobol, Dongping Ma, Michael Valley
Bioluminescent ADMET assays couple targets of interest to the photon emitting reaction of firefly luciferase. Multiplexed cell-based assays measure compound cytotoxicity and induction of P450 transcription and enzyme activity. Cell-free membrane assays measure P450 or monoamine oxidase enzyme activities and their inhibition by test compounds.