title: Anticancer activity of an imageable curcuminoid 1-[2-aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzylidene)-4-piperidone (EFAH).
abstract: 3,5-Bis(2-fluorobenzylidine)-4-piperidone or EF24 is a potent anticancer derivative of curcumin. Using an amine derivative of EF24, we synthesized a hydrazinonicotinic acid conjugate, EFAH, for Tc-99m radiolabelling and single photon emission tomography imaging. The aqueous solubility of EFAH (3.5 mg/mL) was significantly more than that of EF24 (1.2 mg/mL); the octanol/water partition coefficient of EFAH was estimated at log P = 0.33. As an antiproliferative agent, EFAH was as effective as EF24 in suppressing the proliferation of H441, MiaPaCa-2 and Panc-1 cells. Daily intraperitoneal injection of EFAH (5 μg) for 3 weeks in mice carrying xenografts of Panc-1 pancreatic cancer showed a mean tumour volume reduction of 79%; the tumour weight decreased by 82% in the treated group. For imaging and biodistribution, EFAH was labelled with Tc-99m (98% RCY) and intravenously administered in rats. Approximately 23.7% and 14.3% of injected dose accumulated in liver and intestine, respectively, suggesting that EFAH is mostly eliminated by hepatobiliary route. The results indicate that HYNIC modification of EF24 for Tc-99m radiolabelling does not affect its antiproliferative efficacy. For the first time, a visual biodisposition of EF24 in a live animal model has been demonstrated. Such knowledge could be of benefit in developing therapeutic curcuminoids, such as EF24.
authors: Department of Pharmaceutical Sciences and Small Animal Imaging Facility, University of Oklahoma Health Science Center, 1110 N, Stonewall Avenue, Oklahoma City, OK 73117, USA.
authors: Pallavi
authors: P
authors: Lagisetty
authors: Dharmalingam
authors: D
authors: Subramaniam
authors: Kaustuv
authors: K
authors: Sahoo
authors: Shrikant
authors: S
authors: Anant
authors: Vibhudutta
authors: V
authors: Awasthi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
chemical_list: C571719:1-(2-aminoethyl-(6-hydrazinopyridine-3-carbamidyl))-3,5-bis-(2-fluorobenzylidene)-4-piperidone; C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D006834:Hydrazines; D010881:Piperidones; D019275:Radiopharmaceuticals; D013667:Technetium