THEORETICAL INVESTIGATION ON INTERACTION BINDING OF ANALOGS OF AT-1840 TO DOUBLE-STRANDED POLYNUCLEOTIDE

The acetate of ungeremine (AT-1840, lycobetaine) is a new anticancer a gent. Pharmacological studies have revealed that AT-1840 can interact with DNA by intercalation mechanism, preferentially into G-C base pair s. The tetranuclueotide d(CCGG)(2) was selected as target with which A T-1840's analogues interact and their interaction energies have been c alculated in order to investigate the relationship between interaction energy and the pharmacological activity. The calculation results indi cate that there is parallel relationship between interaction energy an d anticancer potency. For the four potent compounds, the binding in fa shion A is better than in fashion B. The electrophilicity of 17-substi tuent was found to be an important factor markedly affecting the inter action of compounds with DNA. According to these results two new compo unds were designed.