## Abstract

This study examined the applicability of various density functional theory (DFT)-based descriptors, such as energy gap (ΔE) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), weighted nucleophilic atomic frontier electron density (WNAFED, F _{i} ^{N}), mean molecular polarizability (α), and net atomic charge (Q _{i}), in quantitative structure-activity relationship (QSAR) studies on a class of important protoporphyrinogen oxidase (Protox) inhibitors including a series of cyclic imide derivatives with various heterocyclic rings and substituents. Our QSAR analysis using the quantum chemical descriptors calculated at the B3LYP/6-31G(d,p) level led to a useful explicit correlation relationship, i.e. pI _{50} = -5.7414 + 0.1424α - 0.0003α ^{2} - 0.4546F _{C.} ^{N} + 0.2974Q _{N.} (n=26, R ^{2}=0.87), showing that descriptors mean molecular polarizability, α, and WNAFED F _{C.} ^{N} of a critical carbon atom and net atomic charge (Q _{i}) in the molecules are most likely responsible for the in vitro biological activity of cyclic imides. It has been shown that the use of the DFT-based quantum chemical descriptors indeed led to a better QSAR equation than that obtained from the use of the corresponding descriptors calculated at a semiempirical PM3 level. The present work demonstrates that the DFT-based quantum chemical descriptors are potentially useful in the future QSAR studies for quantitatively predicting biological activity, and, therefore, the DFT-based QSAR approach could be expected to help facilitate the design of additional substituted cyclic imide derivatives of Protox inhibitors with the potentially higher biological activity.

Original language | English |
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Pages (from-to) | 2099-2105 |

Number of pages | 7 |

Journal | Journal of Chemical Information and Computer Sciences |

Volume | 44 |

Issue number | 6 |

DOIs | |

State | Published - Nov 2004 |

## ASJC Scopus subject areas

- General Chemistry
- Information Systems
- Computer Science Applications
- Computational Theory and Mathematics