DESIGN, SYNTHESIS, DNA-BINDING AND DOCKING STUDY OF 2,4-DIMETHOXY ACRIDONES AS CYTOTOXIC AGENTSAbstract
A series of novel N10 -substituted 2,4-Dimethoxy acridones were synthesized as potent cytotoxic agents. DNA-binding studies of the synthesized compounds were carried out by the HPLC method using Calf thymus DNA (CT – DNA) based on their affinity or intercalation with CT-DNA, measured by binding percentage. The compound 12 bearing planar dimethoxy tricyclic ring linked with butyl pyrazole side chain showed the highest percentage of binding (90.78%) with CT-DNA and showed binding affinity of -6.08 Kcal/mol with the lipophilicity value of 3.33. Compound 8 showed the highest lipophilicity value of 5.09 with a binding affinity of -6.04 Kcal/mol and a percentage of drug binding (80.93%). Compound 5 showed high binding affinity of 7.01 Kcal/mol with percentage of drug binding (66.94%) and lipophilicity value of 3.72. The Binding affinity and percentage of drug binding showed favorable results. The docking outcome was in good agreement with DNA-binding results confirming the DNA binding activity of compounds. The lipophilicity and binding ability of the acridones with CT-DNA showed poor correlation.
Navitha, Narendra B. Gowda and N. K. Sathish *
Department of Pharmaceutical Chemistry, Government College of Pharmacy, Bengaluru, Karnataka, India.
09 October 2021
10 January 2022
05 May 2022
01 July 2022