Structure activity correlation studies of anti-tumour agents based on flavone acetic acid
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In the first part of this thesis (chapters 1-8) the structure/activity (S/A) correlation studies on a class of anti-cancer drugs based on flavone acetic acid (FAA) by means of computer modelling techniques are reported. In particular, semiempirical and ab-initio quantum mechanical calculations have been performed on ten FAAs whose expeirmental anti-cancer activity was known. The results show that some calculated properties such as bond lengths, atomic charges, energies of the HOMO and the atomic orbitals involved in its formation, correlate with the anti-tumour activity. The correlations found were then used on another 38 molecules analogous to FAA whose anti-cancer activity had also been measured and of the 21 active molecules, 20 were predicted to be active by these SA correlations (95% success rate). From this study it also emerged that the pyrone ring may be directly involved in the anti-tumour mode of action of the FAA and it is suggested that vitamin-K may also play a role. The second part (chapter 9) is a study of the dependence of the molecular electrostatic potential on the basis set. From this study it emerged that GEOSMALL and MINI-1 minimal basis sets produce MEPs that are more similar to those obtained with the 6-31G** basis set than the MEP obtained with the STO-NG basis set. GEOSMALL and MINI-1 also give better energies and better properties than STO-NG and their use is recommended when properties of large organic molecules are of interest. Also, from this study it emerged that the use of Mulliken charges for the calculation of the MEP with the point charge approximation is not advisable for it may lead to very different pictures of the electrostatic potential calculated directly from the wave function.
Thesis, PhD Doctor of Philosophy
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