Synthesis, characterization and antitumor activity of new ferrocene incorporated N,N'-disubstituted thioureas.
We report herein the synthesis, structural characterization and activity against human ovarian tumour models: A2780 (parent), A2780(cisR) (resistant to cisplatin) and A2780(ZD0473R) (resistant to the cisplatin analogue denoted as ZD0473) of two ferrocene incorporated N,N'-disubstituted thioureas {1-benzoyl-3-(4-ferrocenylphenyl)thiourea, B16, and 1-acetyl-3-(4-ferrocenylphenyl)thiourea, B3}. Structural characterization has been based on FT-IR, multinuclear ((1)H and (13)C) NMR, elemental analysis and single crystal X-ray diffractometry. Ferrocene-incorporated thioureas may present themselves as a new class of metal-based tumour active compounds. The cyclic voltammetric measurements indicate that B16 undergoes partial intercalation with the CT-DNA whereas B3 undergoes only electrostatic interaction with the same. Partial prevention of BamH1 digestion of pBR322 plasmid DNA that has been interacted with high concentrations of both B16 and B3 indicates that even non-covalent interactions can induce significant conformational changes in the DNA.
Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan.
Bhajan
B
Lal
Amin
A
Badshah
Ataf Ali
AA
Altaf
Muhammad Nawaz
MN
Tahir
Shafiq
S
Ullah
Fazlul
F
Huq
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D055664:Electrochemical Techniques; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D000075163:Metallocenes; D008968:Molecular Conformation; D013890:Thiourea / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005296:Ferrous Compounds; D000075163:Metallocenes; D004247:DNA; D013890:Thiourea; C004998:ferrocene