Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]benzodiazepines as antimitotic agents.
A series of new cinnamido-pyrrolo[2,1-c][1,4]benzodiazepine conjugates (4a-d and 5a-d) and their dimers (6a-d) have been designed, synthesized and evaluated for their biological activity. The anticancer screening of compound 4a by the NCI exhibited significant GI50 values ranging from 68 to 732 nM against 53 of 59 human cancer cell lines tested. Compounds 5a-d and 6a-d have also shown remarkable cytotoxic activity with GI50 values <0.1 microM concentrations in a large number of cell lines. Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in G0 and G2/M phase.
Kamal
Ahmed
A
Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India. ahmedkamal@iict.res.in
Balakishan
G
G
Ramakrishna
G
G
Shaik
T Basha
TB
Sreekanth
K
K
Balakrishna
M
M
Rajender
Dastagiri
D
D
Kalivendi
Shasi V
SV
D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D050256:Antimitotic Agents; D014404:Tubulin; D001569:Benzodiazepines