The potency and aqueous solubility significantly affect the clinical use of Combretastatin
A-4 and phenstatin analogs. A lot of Combretastatin A-4 analogs have good potency but they have
been rejected in clinical trials due to low solubility. In this research work, cheminformatic approaches
i.e., structure activity correlation by rational approach and computational approach (pharmacophore
and atom based 3D QSAR), molecular docking, energetic based pharmacophore mapping
studies have been used to identify significance of amino group substitution at Combretastatin A-4
and phenstatin analogs. Substitution of amino group in Combretastatin A-4 and phenstatin analogs at
R2 or/and R2' or/and R3' exhibited excellent cytotoxic activity with enhanced aqueous solubility. The
amino group increased the polarity of the corresponding structure without compromising its bioactivity.
It is possible in the future to design structural analogs of Combretastatin A-4 and phenstatin with
amino group exhibiting excellent cytotoxic activity with enhanced aqueous solubility.
Keywords: Combretastatin A-4, phenstatin, cheminformatics, pharmacophore, 3D-QSAR, docking.
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