Anti-cancer agents in medicinal chemistry
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Anticancer Agents Med Chem · May 2008
ReviewTargeting poly (ADP) ribose polymerase I (PARP-1) and PARP-1 interacting proteins for cancer treatment.
Cancer is a disease of uncontrolled cellular proliferation. Chemotherapy and radiation therapy are the two main modalities for cancer treatment. However, some cancer types have been found to be refractory to these treatments. ⋯ Since the resistance of cancer cells to DNA damaging agents stems from the modulation of DNA repair pathways, pharmacological inhibition of these pathways has been emerging as an effective tool for cancer treatment. Inhibition of key proteins involved in the molecular cascade of DNA damage detection and repair such as poly (ADP) ribose polymerase I (PARP-1) and its interacting proteins [DNA dependent protein kinase (DNA-PK) and Cockayne syndrome group B (CSB)] has recently proven to be successful for the treatment of various types of cancer cells and tumor xenografts in vitro. This review summarizes some of the recent findings and the potential application of DNA repair inhibitors in cancer treatment.
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Anticancer Agents Med Chem · Apr 2008
ReviewCancer chemoprevention by garlic and its organosulfur compounds-panacea or promise?
Of late medicinal plants and functional foods rich in bioactive phytochemicals have received growing attention as potential agents for cancer chemoprevention. Accumulating evidence from epidemiological studies as well as laboratory data supports the anticancer properties of garlic widely used as a medicinal herb and spice. Garlic and its organosulfur compounds (OSCs) appear to exert their anticarcinogenic effects through multiple mechanisms that include modulation of carcinogen metabolism, inhibition of DNA adduct formation, upregulation of antioxidant defences and DNA repair systems, and suppression of cell proliferation by blocking cell cycle progression and/or inducing apoptosis. Since multiple signaling pathways are dysfunctional in cancer and new oncogenic mutations accumulate with carcinogenic progression, dietary agents such as garlic with its rich array of bioactive OSCs that modulate cancer cascades offer promise as potential chemopreventive and chemotherapeutic agents.
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Anticancer Agents Med Chem · Sep 2007
ReviewPARP inhibitor development for systemic cancer targeting.
Poly(ADP-ribose) polymerase 1 (PARP-1) is a DNA-binding enzyme that is activated by DNA breaks, converting them into an intracellular signal via poly(ADP-ribosyl)ation of nuclear proteins. Negatively charged polymers of ADP-ribose (PAR) attached to PARP-1 itself and histones lead to chromatin relaxation, facilitating the access of base excision/single strand break repair proteins and activating these repair enzymes. ⋯ These novel PARP inhibitors have been shown to enhance the antitumour activity of temozolomide (a DNA-methylating agent), topoisomerase poisons and ionising radiation in advanced pre-clinical studies and are now under clinical evaluation. PARP inhibitors can also selectively kill cells and tumours with homozygous defects in the hereditary breast cancer genes, BRCA1 and BRCA2.
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Anticancer Agents Med Chem · Jan 2007
ReviewSearching for the magic bullet: anticancer platinum drugs which can be accumulated or activated in the tumor tissue.
Cisplatin, carboplatin and oxaliplatin are anticancer drugs, which are efficiently used in the clinics all over the world. Besides a remarkable therapeutic efficacy in a series of solid tumors and outstanding activity of cisplatin against testicular germ-cell cancer, the platinum-based therapy is in part accompanied by a set of severe toxic side-effects. The design of platinum complexes being equipped with an exclusive selectivity for the tumoral tissue and exhibiting a lack of systemic toxicity ('magic bullets') is the great hope in the fight against cancer and also a motor within the expanding field of bioinorganic chemistry. In this review article, two promising strategies, namely accumulation and activation of tumor inhibiting platinum complexes specifically at the tumor site is presented, demonstrating a stepwise approach towards the 'magic bullet' concept propagated by Paul Ehrlich.