Sci Pharm. 2009; 77: 19–32.
Synthesis of Novel 1,3-Diacetoxy-Acridones as Cytotoxic Agents and their DNA-Binding Studies
N. K. SATHISH 1, V. V. S. RAJENDRA PRASAD 1, N. M. RAGHAVENDRA 2, S. M. SHANTA KUMAR 1, Y. C. MAYUR * 1
1 Medicinal Chemistry Research Division, V. L. College of Pharmacy, Raichur-584103, Karnataka, India.
2 Acharya and BM Reddy College of Pharmacy, Bangalore, Karnataka, India.
* Corresponding author. E-mails: mayuryc@yahoo.com or mayuryc@rediffmail.com (Y. C. Mayur).
Abstract
A series of novel substituted acridones (1–15) have been synthesized. Their in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) and human promyelocytic leukemia (HL-60) cell lines has been investigated. The compounds 11, 12, 14 and 15 showed moderate activity against MCF-7 cell lines with IC50 value < 5.83 μM. The compounds 8, 10–12, and 15 showed moderate activity against HL-60 cell lines with IC50 value < 1.75 μM. The DNA-binding properties of the compounds were evaluated based on their affinity or intercalation with CT-DNA measured with absorption titration. The compound 12 bearing planar diacetoxy tricyclic ring linked with butyl piperidine side chain showed highest binding affinity with binding constant (Ki) 10.38 ×10 ×M–1. The examination of the relationship between lipophilicity and cytotoxic properties of acridones showed a poor correlation.
Keywords
1,3-Diacetoxyacridone • Cytotoxicity • MCF-7 • HL-60, DNA-binding • Calf-Thymus DNA.
Received November 4th, 2008 | Accepted December 18th, 2008 | Published Online December 19th, 2008
