Compound 1 (2,3-dichloro-1,4-naphthoquinone) was used as a prototype or a parent compound for comparison with its derivatives as 2-amino-3-chloro-1,4-naphthoquinones (2-11). It was found that compound 4 was the only one that exhibited experimental activity comparable to that of compound 1 (highly active), whereas the rest of the compounds displayed lower potent activity (moderately to weakly active) (Table 1(Tab. 1)). The experimental results indicate that the replacement of the 2-chloro group of 1 with amino phenyl ring leads to compound 3 with a loss of activity (Table S3, Panel 2). The deleterious effects may be due to an alteration of the mass, electronegativity and van der Waals volume of the compound, as indicated by the Mor04m, Mor08e and G1v values (Table S1 and Table S3, Panel 2). A remarkable reduction in G1v but increases in Mor04m and Mor08e were noted for the inactive compound 3 compared to the most potent compound 1, which showed lower Mor04m (1.226) and Mor08e (-0.928) values but higher G1v (0.193) values (Table S1). Such descriptor values are well correlated with the results of the QSAR model, as previously mentioned. However, improved activities were observed when various types of substituents were placed on the 2-amino group (Table S3, Panel 3) or on the phenyl ring of the 2-amino group (Table S3, Panels 4 - 7). In particular, the highly potent activity of the compound 4 is governed by the additional substitution of the CH3 group on the 2-amino group of inactive compound 3, which causes the opposite effect on related descriptors (i.e., Mor04m, Mor08e and G1v) such that it enhances the activity (Table S3, Panel 3). Compound 4 showed a higher G1v value (0.190) but lower Mor04m (1.104) and Mor08e (-0.728) values compared with those of compound 3, which showed a lower G1v (0.619) value but higher Mor04m (1.672) and Mor08e (-0.494) values.