The effect of some new platinum (II) and palladium (II) coordination complexes on rat hepatic nuclear transcription in vitro.
Several new L-amino acid derivatives of 2,2'-bipyridine and 1,10-phenanthroline complexes of platinum (Pt) and palladium (Pd) and a few binuclear 2,2'-bipyridine complexes of these metals were tested for their potential to inhibit rat hepatic nuclear transcription in vitro. Pd complexes were generally more effective inhibitors of transcription than the corresponding Pt complexes. Among Pd-diimine chlorides, the 2,2'-bipyridine complex was nearly 10 times more active than the corresponding 1,10-phenanthroline complex. Both Pt-diimine chlorides, however, showed same level of inhibitory activity. Amino acid derivatives were less inhibitory with respect to the parent metal diimine chlorides except for 1,10-phenanthroline complexes of Pd. For binuclear 2,2'-bipyridine complexes of Pt, the increase in length of linking hydrocarcon chain increased the inhibitory potential of the complex. The mechanism of inhibition of transcription by these metal complexes was sought to be understood by use of actinomycin-D and poly[d(I-C)] to differentiate effect on the two major components of transcription machinery viz. the template and the enzyme. These studies along with studies on reconstituted system of transcription using either pretreated template or enzyme indicate that these metal complexes displayed dual effect on transcription by inhibiting both the template and the enzymes.
Mital
R
R
Department of Chemistry, Indian Institute of Technology, Powai, Bombay.
Shah
G M
GM
Srivastava
T S
TS
Bhattacharya
R K
RK
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*
D000596:Amino Acids; D000970:Antineoplastic Agents; D010984:Platinum; D010165:Palladium; D012313:RNA