Studies on activities, cell up take and DNA binding of four multinuclear complexes of the form: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4-7.
The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied for four multinuclear complexes code named DH4Cl, DH5Cl, DH6Cl and DH7Cl, having the general formula: [[trans-PtCl(NH(3))(2)](2)mu-[trans-Pd(NH(3))(2)-(H(2)N(CH(2))(n)NH(2))(2)]]Cl(4) where n=4, 5, 6 and 7 for DH4Cl, DH5Cl, DH6Cl and DH7Cl, respectively. The compounds are found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R). DH6Cl in which the linking diamine has six carbon atoms is found to be the most active compound. As the number of carbon atoms in the linking diamine is decreased below six and increased above six, the activity is found to decrease, illustrating structure-activity relationship. All the multinuclear compounds are believed to form a plethora of long-range interstrand GG adducts with DNA dictated by the sequence of bases in the DNA strands. Increasing prevention of BamH1 digestion with the increase in concentration of the compounds is due to global changes in DNA conformation brought about by interstrand long-range binding of the compounds with DNA.
Daghriri
Hassan
H
School of Biomedical Sciences, Cumberland Campus, C42, The University of Sydney, East Street, P.O. Box 170, Lidcombe, NSW 1825, Australia.
Huq
Fazlul
F
Beale
Philip
P
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity; D001665:Binding Sites; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D010051:Ovarian Neoplasms; D010165:Palladium / Q000493:pharmacokinetics* / Q000633:toxicity; D010957:Plasmids / Q000378:metabolism; D017671:Platinum Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D015183:Restriction Mapping
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017671:Platinum Compounds; D010165:Palladium