QSAR by Fujita-Ban approach of antileukemic 1-(3-(dialkylamino)propyl)-amino-4-methyl-5H-pyrido4,3-bbenzoeindoles and-benzog indoles

摘要

In vitro antileukemic activities of 1-(3-(dialkylamino)propyl)amino-4-methyl-5H-pyrido4,3-bbenzoeindoles E1 to E14 and -benzogindoles G1 to G12Figure 1) against P388 leukemia cells are subjected to modified de novo analysis (Fujita-Ban method).The'e' fusion series (n=14) explains 92.6 of the variance of the activity while the'g' fusion series (n=11,excluding a compound with an unifrequent substituent)explained only 52.25.Merging the two series,with the tacit assumption of common receptor target and identical mode of action,allows dropping of five compounds having substituents with uncommon positions between the series,extreme skewness of distribution and insignificant coefficients in the individual series.Excluding the possible outliers,the best equation(EV=96.0,R=0.985) is obtained.The equation justifies the underlying assumption of common receptor:a broad flat anchoring site complimenting the fused ring system,possibly having an electron rich centre enhancing hydrogen bonding with 9-OH group of the ligand and an orientation preferring'd' fusion geometry.