Studies on planaramineplatinum(II) compounds of the form [PtL3Cl]Cl where L=planaramine ligand
Arzuman L
Biomedical Science Department
The University of Sydney
Sydney
Australia
Abstract:
Cisplatin is a highly used as anticancer drug although its use is limited due to drug to the presence of side effects and development of drug resistance [1, 2].Currently much research efforts are being applied in designing new platinums that would violate classical structure-activity requirements of cisplatin in one way or another. As such compounds would bind with DNA somewhat differently than cisplatin, the compounds are expected to have altered spectra of activity. This project aims to design new planaramineplatinum(II) compounds of the form [PtL3Cl]Cl where L= planaramine and investigate the compounds for antitumour activity, nature of binding with DNA and mode of transport across the cell membrane. Because of the charged nature of the compounds, they are expected to cross the cell membrane only by carrier-mediated transport. The targeted compounds can only form monofunctional adducts with the DNA and hence the contention that they may have an altered spectrum of activity. This poster will present results on the activity of the compounds and synergism from the combination of the compounds with cisplatin. Elemental analyses and spectral studies are employed to characterize the compounds. Activity of the compounds in ovarian cancer cell lines is determined using MTT reduction assay. Combination studies are done using a number of time sequences.
References:
1. Wang, D., Lippard, S. J. 2005. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 4: 307-320.
2. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22: 7265-7279.
