A DFT Study of the Relationships Between Electronic Structure and Peripheral Benzodiazepine Receptor Affinity in a Group of N,n-Dialkyl-2-Phenylindol-3-Ylglyoxylamides

Abstract

We present here the results of a Density Functional Theory study of the relationships between electronic structure and peripheral benzodiazepine receptor affinity for a group of n,n-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives. As expected for a receptor that evolved over many millions of years, the interaction is charge-and orbital-controlled because it involves net charges and reactivity indices from definite molecular orbitals. The conditions for high receptor affinity are obtained and commented on. A partial pharmacophore model is suggested and discussed. This is the first time that an all-electron calculation combined with a model-based method is employed in QSAR studies.

Model-Based Quantum-Chemical Study of the Uptake of Some Polychlorinated Pollutant Compounds by Zucchini Subspecies

“…This process is also orbital-controlled. chlorine substitution patterns 35 . This interaction is also orbital-controlled.…”

“…As expected, ZINDO/1 gave good results when applied to the interaction of a group of 3-substituted morphinans with μ, δ and κ opioid receptors 51 , and for the inhibition of wild-type and drug-resistant HIV-1 reverse transcriptase by some thiazolidenebenzenesulfonamide derivatives 52 . The problem of obtaining good numerical values for the NSD index with ab initio and DFT calculations has not yet been solved but there are some promising results 35,53 . We need to stress that the correct choice of more primitive methods (Extended Hückel Theory) can be very helpful in interpreting experimental results [54][55][56] .…”

“…This line of thought started with the work of Agin et al during the 1960s 27 , was continued by Cammarata 28 , crystallized in the work of Peradejordi 29 and was extended by one of us [30][31][32] . Its application to the analysis of experimental data on drug-receptor interactions showed [33][34][35][36][37] , beyond all reasonable doubt, that it has predictive capacity 38 and is even able to detect erroneous experimental data 39 . On the other hand, the lipophilic properties of molecules govern the penetrability of biological membranes and the partition between organic and aqueous phases.…”

Quantum Chemical Study of the Relationships Between Electronic Structure and Pharmacokinetic Profile, Inhibitory Strength Toward Hepatitis C Virus Ns5b Polymerase and HCV Replicons of Indole-Based Compounds

“…We have called them orientational parameters 49 . This model has shown, beyond all reasonable doubt, that it can shed light on the detailed structure of the drugreceptor interaction for several kind of biomolecules and receptors 48,[56][57][58][59][60][61][62][63][64][65][66] , that it has predictive capacity [67][68][69] and is even able to detect erroneous experimental data 70 . The last paper employing this method and not belonging to our group was published in 1979 71 .…”

“…Its application gave good results when applied to drug-receptor interaction studies 62 and biological activities (inhibition of wild-type and drug-resistant HTV-1 reverse transcriptase 63 , accumulation of polychlorinated molecules 76 and inhibitory activity against some effects of HIV-1 and H1N1 viruses 77 ). It is worth mentioning that, in general but not always, semiempirical methods give better QSAR results that Hartree-Fock or Density Functional ones 65,81 .…”