Phosphonate-linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.
Pyrrolobenzodiazepine-diethylphosphonate conjugates have been designed and synthesized that link through two different types of spacers that are simple alkane chain and also a piperazine moiety side-armed with the alkane chains. These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity.
Kamal
Ahmed
A
Biotransformation Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh 500 007, India. ahmedkamal@iict.res.in
Kumar
P Praveen
PP
Seshadri
B N
BN
Srinivas
O
O
Kumar
M Shiva
MS
Sen
Subrata
S
Kurian
Nisha
N
Juvekar
Aarti S
AS
Zingde
Surekha M
SM
D000586:Amination; D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D063065:Organophosphonates / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013696:Temperature
D063065:Organophosphonates; D011758:Pyrroles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D004247:DNA; C427203:calf thymus DNA