Design, synthesis, and in vitro antiproliferative activity of benzimidazole analogues for radiopharmaceutical efficacy.
The synthesis of eight ligands by using 2-amino benzimidazole with different mono/bis aldehydes is described herein. The final products were characterized by spectral techniques such as FT-IR, (1)H NMR, and EI-Mass. The structure-activity relationships of the benzimidazole derivatives are also reported. Studies on the complexation of the ligands with (99m)Tc were optimized by using stannous tartrate as reducing agent under various reaction conditions. The radiochemical stability was >or=95% for all the complexes, and they were to be stable for 12-14 hours in serum. Most of the ligands showed fast blood clearance. Biodistribution studies of the (99m)Tc complexes of these ligands showed no significant uptake in the brain or in the heart, and the clearance was mainly through the hepatobiliary system. Among the eight compounds evaluated for their antiproliferative activity in vitro, L(8) produced good activity against the cancer cell lines A549 and PC-3.
Singh
Sweta
S
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Ojha
Himanshu
H
Tiwari
Anjani K
AK
Kumar
Nitin
N
Singh
Bachcha
B
Mishra
Anil Kumar
AK
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D006321:Heart / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D001562:Benzimidazoles; D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals