Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.
A series of triazolobenzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These compounds have exhibited significant cytotoxicity against most of the cell lines examined. Compound 5a displays GI(50) values from 1.83 to 2.38 microM against seven human tumour cell lines, and is identified as a promising lead compound from this series. Their DNA thermal denaturation studies have also been carried out, and one of the compounds 5c elevates the DNA helix melting temperature of the CT-DNA by 2.6 degrees C after incubation for 36 h.
Kamal
Ahmed
A
Chemical Biology Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India. ahmedkamal@iict.res.in
Khan
M Naseer A
MN
Srikanth
Y V V
YV
Reddy
K Srinivasa
KS
Juvekar
Aarti
A
Sen
Subrata
S
Kurian
Nisha
N
Zingde
Surekha
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001581:Benzothiadiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009062:Mouth Neoplasms / Q000188:drug therapy; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D000970:Antineoplastic Agents; D001581:Benzothiadiazines; D004273:DNA, Neoplasm; D011758:Pyrroles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D004247:DNA; C427203:calf thymus DNA