- Synthesis of 2-[11C]methoxy-3,17β-O,O-bis(sulfamoyl) estradiol as a new potential PET agent for imaging of steroid sulfatase (STS) in cancers
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Steroid sulfatase (STS) catalyzes the hydrolysis of steroid sulfates to estrones, the main source of estrogens in tumors. Carbonic anhydrase II (CAII) is highly expressed in red blood cells through a coordination of the monoanionic form of the sulfamate moiety to the zinc atom in the enzyme active site, and CAII is highly expressed in several tumors. 2-Methoxy-3,17β-O,O- bis(sulfamoyl)estradiol (5) is a dual-function STS-CAII inhibitor inhibited STS with 39 nM IC50 value selectively over CAII with 379 nM IC 50 value. This compound exhibited potent antiproferative activity with mean graph midpoint value of 87 nM in the NCI 60-cell-line panel, and antiangiogenic in vitro and in vivo activity in an early-stage Lewis lung model as well. The compound has been recently developed as a multitargeted anticancer agent. Both STS and CAII are over-expressed in cancers and have become attractive targets for cancer treatment and molecular imaging of cancer. Here we report the first design and synthesis of 2-[11C]methoxy-3,17β- O,O-bis(sulfamoyl)estradiol ([11C]5) as a new potential imaging agent for biomedical imaging technique positron emission tomography (PET) to image STS in cancers. The authentic standard 5 was synthesized from 17β-estradiol by published procedures in 5 steps with 40% overall chemical yield. The precursor 2-hydroxy-3,17β-O,O-bis(sulfamoyl)estradiol (14a) for radiolabeling was synthesized from 17β-estradiol in 10 steps with 5% overall chemical yield. The target tracer [11C]5 was prepared from the precursor 14a with [11C]CH3OTf through O-[ 11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) purification in 40-50% radiochemical yields based on [ 11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.
- Wang, Min,Xu, Lu,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
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p. 864 - 870
(2012/07/14)
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- Estradiol conjugates and uses thereof
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A conjugated prodrug of an estradiol compound conjugated to a biological activity modifying agent.
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Page/Page column 13
(2010/11/08)
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- Synthesis of 2-alkoxyestradiols
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Disclosed is a method of preparing a compound represented by the following structural formula: The method comprises reacting bromine (Br2) and an aliphatic organic acid with a compound represented by the following structural formula: R1 and R2 are each independently a hydroxyl protecting group.
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- Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth
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A new series of estradiol analogs was synthesized in an attempt to improve on the anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of tubulin polymeriza
- Cushman, Mark,He, Hu-Ming,Katzenellenbogen, John A.,Varma, Ravi K.,Hamel, Ernest,Lin, Chii M.,Ram, Siya,Sachdeva, Yesh P.
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p. 2323 - 2334
(2007/10/03)
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- Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site
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In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 2-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inh
- Cushman,He,Katzenellenbogen,Lin,Hamel
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p. 2041 - 2049
(2007/10/02)
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