| 主权项 |
1. A method for inhibiting the invasiveness of tumor cells in a subject, said method comprising contacting said cells with a pharmaceutically effective amount of a compound, wherein said compound has Formula I:or a stereoisomer, tautomer, racemic, pro- or predrug, salt, hydrate, or solvate thereof, wherein:
A1, A2 and A3 are independently selected from C and O; R1, R2, R3, R4, R5, and R6 are each independently selected from —H, -halo, —C1-6 alkyl, and —O—C1-6 alkyl; and x and y are each independently selected from 1 or 2; andwherein said compound has a predicted lowest active concentration of 0.1 μM or less as predicted by an in silico method to predict the anti-invasive activity of said compound; said in silico method comprising the steps of:
(1) determining theoretical molecular descriptors for said compound, wherein the theoretical molecular descriptors comprise:
(a) maximal antibonding contribution of one molecular orbital (D1),(b) partial surface area for atom C (D2),(c) final heat of formation/# atoms (D3),(d) XY Shadow/XY Rectangle (D4),(e) minimum 1-electron reaction index for an oxygen atom (D5), and(f) polarity parameter (D6); and (2) determining log cmin for said compound, wherein log cmin is determined in accordance with the following Equation:
log cmin=−58.90+(28.63×D1)−(16.29×D2)+(1.093×D3)+(9.904×D4)−(116.3×D5)+(17.01×D6) wherein:
when log cmin is >−1.5 and ≦−0.5, said compound is predicted to have anti-invasive activity at a lowest active concentration of about 0.1 μM,when log cmin is >−2.5 and ≦−1.5, said compound is predicted to have anti-invasive activity at a lowest active concentration of about 0.01 μM, andwhen log cmin is ≦−2.5, said compound is predicted to have anti-invasive activity at a lowest active concentration of <0.01 μM. |
