Current Medicinal Chemistry - Volume 18, Issue 28, 2011

The azetidinone core-structure offers a unique approach to the design and synthesis of new derivatives with unique biological properties. During the last two decades researches convincingly demonstrated that the prospect of structural modifications of monocyclic β-lactams with specific substituents is an effective procedure for the detection and improvement of important pharmacological effects different from antibacter Read More

The development of new treatments for mood disorders, as anxiety and depression, is based on identification of neural substrates and the mechanisms underlying their etiology and pathophysiology. The heterogeneity of mood disorders indicates that its origin may lie in dysfunction of multiple brain regions (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex). The hippocampus of patie Read More

Alzheimer's disease (AD) is a highly complex and rapidly progressive neurodegenerative disorder characterized by the systemic collapse of cognitive function and formation of dense amyloid plaques and neurofibrillary tangles. AD pathology is derived from the cholinergic, amyloid and tau hypotheses, respectively. Current pharmacotherapy with known anti-cholinesterases, such as Aricept® and Exelon®, only offer sym Read More

Alcoholism is a multifarious and ongoing disease tightly related to the amount of alcohol ingested, the drinking pattern, the history of alcohol drinking and the individual features, such as some genetic traits. Worldwide alcohol is the necessary cause of approximately 60 diseases and causes circa 2.5 million deaths every year. Studies show that alcohol interacts with brain neurotransmission in a complex manner. Dopa Read More

Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. HIF-1, a heterodimer consisting of a constitutively expressed β subunit and an oxygen-regulated α subunit, regulates a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The activity of HIF-1 is controlled by post-translational modifications Read More

Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the Read More

Major depression is a common mood disorder that affects overall health; currently, almost all of the available antidepressants have the same core mechanisms of action through promotion of serotonin or noradrenaline function in the brain. The major limitation of today's antidepressants is that chronic treatment (3 - 6 weeks) is required before a therapeutic benefit is achieved. More effective and faster treatments for depressio Read More

Checkpoint kinase 2 is a serine/threonine protein which functions as an important transducer in apoptosis or DNA repair following activation by DNA damage. Inhibition of checkpoint kinase 2 is thought to sensitize p53-mutated or p53-deficient cancerous cells but protect normal tissue following DNA-damage caused by ionizing radiation or chemotherapeutic agents. The development of checkpoint kinase inhibitors for the treatme Read More

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. However, there has been increasing interest in developing novel molecularly targeted agents in HCC due to the accumulation of knowledge of cell signaling and molecular carcinogene Read More

Topoisomerase I (Top1) represents an important target of active interest in developing novel anticancer agents. Camptothecin derivatives are the only class of clinically approved Top1 inhibitors and show potent efficacy in anticancer therapy. However, there are also several major limitations for them, such as poor chemical stability, drug resistance, long infusions and side effects. To overcome the drawbacks of the camptothecins Read More

Ribosome inactivating proteins (RIPs) are toxic RNA N-glycosidases that cleave an adenine-ribose glycosidic bond at position adenine4324 with the conserved ricin/α-sarcin loop in the eukaryotic 28S ribosomal RNA. RIPs have captured the attention of botanists, biochemists, and drug discoverers, due to their diverse potent defensive activities, and inter alia, their antitumor and anti-HIV activities. Out of the 145 families Read More