STUDIES ON THE RELATIONSHIP OF ANTITUMOR ACTIVITY AND THE ELECTRONIC STRUCTURE OF RIBONUCLEOTIDE REDUCTASE INHIBITORS

By using the CNDO/2 quantum chemistry method,32 substituted hydroxamicacids,6 substituted benzamides and 9 substituted methyl benzoates have been calculated.Among them44 compounds were studied by step regression method. Two quantitative structure-(ribonucleotidereductase inhibitory) activity relationships of two groups(hydroxamic acids and benzamides ,methylbenzoates)were obtained. They were(1) PC=3.00—2.74 CQS—0.15 E_HOMO+0.22 SHEP forsubetituted hydroxamic acids and(2) PC=10.06—0.96 CQS+1.07 E_LUMO+0.66 SHEP forsubetituted benzamides and methyl benzoates. The results show that the quantum chemical indexes inthe two QSAR affected the inhibitory activity to similar degree and the mechanism of inhibition ofribonucleotide reductase by inhibitors involves metal chelation. Furthermore ,the effects of thestructure of 35 compounds on the life span of L₁₂₁₀ leukemia-bearing mice were studied by patternrecognition method. The antitumor activity classification figure obtained by four parameters π,CQS,ELUMO and SHEP, is satisfactory. This indicates that the antitumor activities of these compounds arethe result of inhibiting ribonucleotide reductase which is governed by the speed and extent of thesecompounds to reach the acceptor.