Current pharmaceutical design
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The well-known opioid agonists, oxycodone and oxymorphone, and the opioid antagonists, naloxone and naltrexone, are commonly used clinical agents and research tools in the opioid field. They belong to the class of morphinan-6-ones, and produce their pharmacological effects by interacting with opioid receptors, i.e. mu (MOR), delta (DOR) and kappa (KOR). The search for potent agonists and antagonists has continuously engaged the interest of pharmaceutical research, aiming for the identification of safer therapeutic agents or discovery of opioids with novel therapeutic properties and with lesser unwanted side effects. ⋯ In this work, the development of 6-amino and 6-guanidino substituted 14-alkoxymorphinans, including the synthesis and pharmacological investigations is presented. The new approach represented by the introduction of amino and guanidino groups into position 6 of the morphinan skeleton of 14-O-methyloxymorphone, led to compounds with high efficacy, MOR affinity and selectivity, which act as potent antinociceptive agents. Altogether, as a consequence of target drug design and synthetic efforts in the field of morphinan-6-ones, we achieve a better understanding of the function of the opioid system, and such efforts may open new avenues for further investigations.
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Lung cancer is the leading cause of mortality world-wide. Non Small Cell Lung Cancer (NSCLC) is a particularly aggressive cancer, the optimum management of which is still being determined. In the next years modest survival improvement can be expected by chemotherapy. ⋯ A number of studies suggest that the PI3K/Akt signaling pathway is central to NSCLC growth and survival. Given the importance of activated PI3K signaling in cancer, several PI3K inhibitors are currently one of the most recent drug targets in oncology, with several small molecules in early stages of clinical development. This review will focus on the role of EGFR, ALK, MET, and PI3K inhibitors in the treatment of NSCLC.
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Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of foodstuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. ⋯ However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently available evidence regarding resveratrol's effects on humans obtained from randomized clinical trials. In addition, we will provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug.
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The metabolic syndrome (MetS) is a cluster of risk factors including obesity, insulin resistance, dyslipidemia, elevated blood pressure and glucose intolerance. The MetS increases the risk for cardiovascular disease (CVD) and type 2 diabetes. Each component of the MetS causes cardiac dysfunction and their combination carries additional risk. ⋯ In contrast, large scale clinical trials using antioxidants therapies for the treatment of CVD have been disappointing because of the lack of efficacy and undesired side effects. The focus of this review is to summarize the current knowledge about the mechanisms underlying cardiac dysfunction in the MetS with a special interest in the role of oxidative stress. Finally, we will update the reader on the results obtained with natural antioxidant and mitochondria-targeted antioxidant therapies for the treatment of CVD in the MetS.
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Recently, many studies have shown a decrease in myocardial damage in patients undergoing coronary artery bypass surgery where the anesthetic agent used was sevoflurane compared with propofol. The basis for this protective effect of the myocardium occurs through the mechanisms of preconditioning and postconditioning of halogenated agents. Both relate to the benefit of prior or subsequent administration of the drug (halogenated anesthetic agent) to the harmful stimulus for myocardial cells. ⋯ This device has proven useful to facilitate the treatment of pathological conditions. The object of our review is to determine if there are beneficial effects to extending exposure to halogenated agents in the immediate post-operative period. In the post-operative phase, the pathological myocardium is in a reperfusion process in the coronary microcirculation and expression of certain receptors and chemical mediators can reduce potential injury secondary to reperfusion of previously hibernating and/or stunned tissue.