Hansch analysis of anticancer activities of C2-modified paclitaxel analogs against human ovarian carcinoma 1A9, human colon carcinoma HCT116 and human burkitt lymphoma CA46 cell lines

Abstract

Anticancer activities, recently reported by Kingston <i>et </i><i>al, </i>of paclitaxel and its thirty analogs, having substitution(s) on the phenyl ring of 2-benzoyloxy moiety, against human ovarian carcinoma 1A9, human colon carcinoma HCT116 and human burkitt lymphoma CA46 cell lines have been subjected to QSAR analyses by extrathermodynamic approach of Hansch. The aims of the study are to explore the effects of the phenyl ring substituents on the activities and to unravel the quantitative relations of the activities with physico-chemical parameters of the substituents. For the activity against ovarian carcinoma, presence of <i>meta </i>and absence of <i>para </i>substituents on the phenyl ring (with

Respect to the ester linkage on the 2-position of taxane skeleton) has been found to be conducive to the activity. Molar refractivity and electronic parameter (Hammett ϭ ) of the <i>meta </i>substituents show parabolic relationships with the activity. In case of the activity against colon carcinoma, <i>para </i>substitution is not preferred. However, Iipophilicity of the <i>para</i> substituent, If present, has been found to favour to the activity which was further negatively contributed by square term of molar refractivity of the <i>m</i><i>eta </i>substituents. In the relation best obtained, the activity against burkitt lymphoma is found to be negatively contributed by square term of molar refractivity of the <i>meta </i>substituents and those of electronic parameters (Hammett ϭ) of the <i>para </i>and <i>meta </i>substituents. The differences among the equations relating activity against three cell lines

with physico-chemical parameters suggest that there might be some differences among the receptor structures.