Abstract:
:In the early 1960s, inorganic pyrophosphate (PPi) was found to be present in body fluids and to act as a natural inhibitor of calcification by its interaction with hydroxyapatite. In addition to inhibiting the formation of calcium phosphate, PPi also inhibited dissolution of hydroxyapatite crystals, which made it interesting for pharmacologic applications in the treatment of diseases associated with excessive bone resorption. However, PPi is metabolically unstable because of rapid hydrolysis of the P-O-P backbone by hydrolytic enzymes in the gastrointestinal tract. In the search for more stable analogues of PPi, attention turned to the chemical class of bisphosphonates (BPs). The first BPs were synthesized in the 19th century and widely used for industrial applications. Bisphosphonates are formally derived from PPi by replacement of the bridging oxygen atom by a carbon atom, resulting in a P-C-P moiety that is resistant to hydrolysis. In addition to its decisive role in stability, the central carbon atom also provides an attachment point for 2 additional substituents (R¹ and R²). While R¹ is preferentially a hydroxy group, allowing such derivatives to act as powerful tridentate ligands for calcium (bone hook), R² is mainly responsible for antiresorptive potency. The clinically available BPs can be divided into 2 subclasses based on their structure and molecular mechanism of action. The simple, non-nitrogen-containing derivatives can be incorporated into non-hydrolyzable cytotoxic ATP analogues. The more potent nitrogen-containing BPs inhibit FPPS, a key enzyme in the mevalonate pathway. Details of this crucial molecular interaction have recently been elucidated. Members of this class have a wide therapeutic window between therapeutic inhibition of bone resorption and undesired inhibition of bone formation, and several have found widespread use for the treatment of benign and malignant bone disease.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
Widler L,Jahnke W,Green JRdoi
10.2174/187152012799014959subject
Has Abstractpub_date
2012-02-01 00:00:00pages
95-101issue
2eissn
1871-5206issn
1875-5992pii
BSP/ACAMC/E-Pub/ 00233journal_volume
12pub_type
杂志文章,评审abstract::As chemotherapy with temozolomide is far from providing satisfactory clinical outcomes for patients with glioblastoma, more efficient drugs and drug combinations are urgently needed. The anti-malarial artesunate was previously shown to exert a profound cytotoxic effect on various tumor cell lines including those deriv...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/18715206113136660340
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abstract::As cancers are one of the most important causes of human morbidity and mortality worldwide, researchers try to discover novel compounds and therapeutic approaches to decrease survival of cancer cells, angiogenesis, proliferation and metastasis. In the last decade, use of special phytochemical compounds and flavonoids ...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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abstract::Polyphenol-protein interaction (PPI) is reversible in that polyphenol-protein complex can be dissociated and release the free polyphenols. The aim of this study is to evaluate the contribution of polyphenol-protein interaction on improving the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity of polyphe...
journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2012-10-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2018-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underl...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200318094618
更新日期:2020-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,已发布勘误
doi:10.2174/187152061808181112151244
更新日期:2018-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152012800228643
更新日期:2012-05-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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doi:10.2174/1871520616666151111115809
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Tumor recurrence and metastasis are still leading causes of cancer mortality worldwide. The influence of traditional treatment strategies against metastatic tumors may still be limited. To search for novel and powerful agents against tumors has become a major research focus. In this study, Artemisinin (ARM),...
journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2020-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Glucosamine is a widely prescribed dietary supplement used in the treatment of osteoarthritis. In the present study, the chemoprotectant ability of glucosamine was evaluated against cisplatin-induced genotoxicity and cytotoxicity in rat bone marrow cells. METHODS:Glucosamine was orally adminis...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2009-10-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2006-05-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-03-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2011-05-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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doi:10.2174/1871520617666170522120200
更新日期:2017-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2015-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2019-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
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更新日期:2012-09-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2016-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2015-01-01 00:00:00
abstract::Garlic (Allium sativam L.) is widely used in traditional herbal remedies and alternative medicine. The potential health benefits of garlic are largely attributed to its metabolic byproducts. Extensive in vivo and in vitro studies has demonstrated that the garlic derivatives possess anti-cancer effects, but the underly...
journal_title:Anti-cancer agents in medicinal chemistry
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