Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing ability of 2,5-diaryloxadiazole-pyrrolobenzodiazepine conjugates.
A series of 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates have been prepared and evaluated for their anticancer activity. These conjugates have shown promising activity with GI50 values ranging from <0.1 to 0.29 microM. It is observed that some of these conjugates particularly 4a, 4d, 4i and 4l exhibit significant anticancer activity. Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates.
Kamal
Ahmed
A
Chemical Biology Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. ahmedkamal@iict.res.in
Dastagiri
D
D
Ramaiah
M Janaki
MJ
Bharathi
E Vijaya
EV
Reddy
J Surendranadha
JS
Balakishan
G
G
Sarma
Pranjal
P
Pushpavalli
S N C V L
SN
Pal-Bhadra
Manika
M
Juvekar
Aarti
A
Sen
Subrata
S
Zingde
Surekha
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008928:Mitochondria / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D010069:Oxadiazoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D001569:Benzodiazepines; D051357:Cyclin-Dependent Kinase 2; D020169:Caspases