A Theoretical Study of the Relationships between Electronic Structure and Anti-inflammatory and Anti-cancer Activities of a Series of 6,7-substituted-5,8-Quinolinequinones
Juan S. Gómez-Jeria *
Quantum Pharmacology Unit, Department of Chemistry, Faculty of Sciences, University of Chile. Las Palmeras 3425, Nuñoa, Santiago 7800003, Santiago, Chile
*Author to whom correspondence should be addressed.
Abstract
We report the results of the search of quantum-chemical model-based relationships between electronic structure and anti-inflammatory and antiproliferative activity against HL60 and T-cells of a group of 6,7-substituted-5,8-quinolinequinones. The wave functions and local atomic reactivity indices were obtained at the ab initio Hartree-Fock 6-311G (d,p) level of theory. We found and discussed several significant relationships explaining the variation of anti-inflammatory and anti-proliferative activity in terms of the variation of very definite and distinct sets of local atomic reactivity indices belonging to specific atoms of a common molecular skeleton. The variation of anti-inflammatory and anti-cancer activities seems to occur through very different mechanisms. It is shown that σ molecular orbitals localized on certain atoms could play an important function in controlling biological activity. The working hypothesis stating that a model built for in vitro drug-receptor interactions is useful for the study of other biological activities is supported by the results presented here.
Keywords: 6,7-substituted-5, 8-quinolinequinones, QSAR, local atomic reactivity indices, anti-cancer activity, anti-inflammatory activity, anti-proliferative activity, Quantum Chemistry