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

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.