Mini Reviews in Medicinal Chemistry - Volume 13, Issue 2, 2013

Objective: Piper has been used for long timelike condiment and food, but also in traditional medicine around of the world. This work resumes the available and up to date work done on members of the Piperaceae family and their uses for therapeutic purposes. Methods: Information on Piper genus was gathered via internet using scientific databases such as Scirus, Google Scholar, CAB-abstracts, MedlinePlus, Pubmed, SciFinder, Scopus and Web of Science. Results: The largeleafed perennial plant Piper is used for its spicy aromatic scent and flavor. It has an important presence in the cuisine of different cultures. Another quality of these plants is their known medicinal properties. It has been used as emollient, antirheumatic, diuretic, stimulant, abortifacient, anti-inflammatory, antibacterial, antifungal and antidermatophytic. A survey of the literature shows that the genus Piper is mainly known for its alkaloids with cytotoxic, chemopreventive, antimetastatic and antitumor properties in several types of cancer. Studies of its alkaloids highlight the existence of various potential leads to develop new anti-cancer agents. Modern pharmacology studies have demonstrated that its crude extracts and active compounds possess wide pharmacological activities, especially asantioxidant, anti-depressive, hepatoprotective, antimicrobial, anti-obesity, neuropharmacological, to treat cognitive disorders, anti-hyperlipidemic, anti-feedant, cardioactive, immuno-enhancing, and anti-inflamatory. All this evidence supporting its traditional uses. Aim of the review: This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of Piper together with its toxicology, and discusses the possible trend and scope for further research on Piper in the future.

The adhesion of cells to vertically aligned TiO2 nanotubes is reviewed. The attraction between a negatively charged nanotube surface and a negatively charged osteoblast is facilitated by charged protein-mediators like proteins with a quadrupolar internal charge distribution, fibronectin and vitronectin. It is shown that adhesion and spreading of osteoblasts on vertically aligned TiO2 nanotube surfaces depend on the diameter of the nanotubes. Apparently, a small diameter nanotube surface has on average more sharp convex edges per unit area than a large one, leading to stronger binding affinity on its surface.

Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil, rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi, by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty acid mainly found in the Mediterranean diet.

Several chemical elements are required by living organisms in addition to the four elements carbon, hydrogen, nitrogen and oxygen usually present in common organic molecules. Many metals (e.g. sodium, potassium, magnesium, calcium, iron, zinc, copper, manganese, chromium, molybdenum and selenium) are known to be required for normal biological functions in humans. Disorders of metal homeostasis and of metal bioavailability, or toxicity caused by metal excess, are responsible for a large number of human diseases. Metals are also extensively used in medicine as therapeutic and/or diagnostic agents. In the past 5000 years, metals such as arsenic, gold and iron have been used to treat a variety of human diseases. Nowadays, an ever-increasing number of metal-based drugs is available. These contain a broad spectrum of metals, many of which are not among those essential for humans, able to target proteins and/or DNA. This mini-review describes metal-containing compounds targeting DNA or proteins currently in use, or designed to be used, as therapeutics against cancer, arthritis, parasitic and other diseases, with a special focus on the available information, often provided by X-ray studies, about their mechanism of action at a molecular level. In addition, an overview of metal complexes used for diagnosing diseases is presented.

Increased risk of fungal diseases in immunocompromised patients, emerging fungal pathogens, limited repertoire of antifungal drugs and resistance development against the drugs demands for development of new and effective antifungal agents. With greater knowledge of fungal metabolism efforts are being made to inhibit specific enzymes involved in different biochemical pathways for the development of antifungal drugs. Chitin synthase is one such promising target as it is absent in plants and mammals. Nikkomycin Z, a chitin synthase inhibitor is under clinical development. Chitin synthesis in fungi, chitin synthase as a target for antifungal agent development, different chitin synthase inhibitors isolated from natural sources, randomly synthesized and modified from nikkomycin and polyoxin are discussed in this review.

The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family. PEA was identified more than five decades ago and was shown to reduce allergic reactions and inflammation in animals along with influenza symptoms in humans. Interest in this compound faded, however, until the discovery that one of its structural analogs, anandamide (arachidonoylethanolamide), serves as an endogenous ligand for cannabinoid receptors, the molecular target of Δ9-tetrahydrocannabinol in marijuana. Since this finding, PEA has been shown to inhibit peripheral inflammation and mast-cell degranulation, as well as to exert neuroprotective and antinociceptive effects in rats and mice. These actions are also mediated by PPAR-α activation and are accompanied by a decrease in nitric oxide production, neutrophil influx, and expression of proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition to the hypothesis that PEA has potent immunoregulatory properties, recent data have demonstrated that PEA may also play a key role in the regulation of complex systems involved in the inflammatory response, pruritus, neurogenic and neuropathic pain. In this review, we discuss briefly the present understanding therapeutic mechanisms of PEA and the novel possible PEA clinical use for the treatment of several inflammatory diseases and trauma.

Curcumin (diferuloylmethane) is a yellow polyphenol found in the rhizome of the annual herb turmeric (Curcuma longa) belonging to the family Zingiberaceae. Its interaction with a huge number of molecular targets like cytokines, growth factors, transcription factors, receptors, pro-inflammatory enzymes, protein kinases and adhesion molecules has been studied extensively. Interaction of curcumin with nucleic acids has been the focus of extensive research in recent years. Curcumin is observed to be genotoxic and antigenotoxic agent in time and concentration dependent manner. Curcumin and its derivatives either alone or as metal complexes have been reported to bind directly to DNA. The interactions are mainly as DNA minor groove binding or as DNA intercalating agents. The similarity in the shape of curcumin to DNA minor groove binding drugs is the motivation for exploring its binding to DNA minor grooves. Thus curcumin is a “double edged sword”: having therapeutic potential as a minor groove binder but at the same time it may cause DNA damage in the cell at high concentration. The purpose of this review is to summarize the current information related to interaction of curcumin metal complexes and its derivatives with nucleic acids and the implication such interaction can have on therapeutics.

Platinum complexes such as cisplatin and caboplatin are widely used in cancer chemotherapy. However, their clinical applications are substantially limited by unexpected toxic side effects. In this review, we discuss the current progress on the design and synthesis of estradiol-linked platinum complexes as the targeted antitumor drugs. Many of them display a high antitumor activity against the growth of breast cancer cell lines in vitro. The estradiol-linked platinum complexes could be used as target therapeutics for breast cancer.

This review addressed the adverse effects of the frequently-used recreational drug, ketamine through using mice and monkey models. Our laboratory has documented initially that ketamine can induce the formation of hyperphosphorlated tau (hypertau), which is a hallmark of Alzheimer's disease (AD), in the cerebral cortex of both mice and monkeys as well as apoptosis in neurons in these species. Besides the cerebral cortex, other centers in the central nervous system (CNS) and peripheral nervous system (PNS) are also influenced by ketamine. Cerebellum was found to be down-regulated in both mice and humans after long-term of ketamine administration and it was caused by the apoptosis of Purkinje cells. Deleterious effects in other organs reported in long-term ketamine users include of kidney dysfunction leading to proteinuria, fibrosis of the urinary bladder and reduction in size of the urinary bladder leading to frequent urination, increase of liver fibrosis and cardiac problems such as premature ventricular beats. Moreover, ketamine is usually co-administrated with other chemicals such as caffeine or alcohol. It has been reported increased harmful effects when ketamine was used in combination with the above substances. Mechanisms of damages of ketamine might be due to 1) up-regulation of NMDA receptors leading to overestimation of glutamatergic system or 2) the metabolite of ketamine which was a hydroquinone exerted toxicity.

Reactive oxygen species/nitrogen species (ROS/RNS) are major causative agents of oxidative stress related diseases such as neurodegenerative, cancer, cardiovascular, and inflammation via intracellular signal transduction pathways. Synthetic modification of antioxidants and development of hybrid compounds by conjugation or integration of two or more moiety opened a new era in development of antioxidant based therapeutics. In this review, our attention is focused on structural, chemical and biochemical feature of free radicals, description of mechanistic modulation in signaling pathways by antioxidants and establishment of relationship between structural and biological accepts of antioxidant hybrid systems (1,2-dithiolone, α,β-unsaturated carbonyl, cinnamate based hybrids and miscellaneous hybrids).

In recent years, pharmaceutical chemists have synthesized large numbers of andrographolide derivatives, which bear important biological activities such as anti-inflammatory, antibacterial, antivirus, antitumor, antidiabetic, and antifeedant. Consequently, corresponding SARs were increasingly obvious. This paper aimed to review all the available literature in this field, highlighting the significant achievements on the structural modification and SARs of andrographolide and its derivatives.

Rupestonic acid (isolated from the Chinese traditional medicine Artemisia rupestris L.) is a sesquiterpene with multifunctional groups and possess higher activity against influenza virus B. In order to improve the biological activity of rupestonic acid, many derivatives have been synthesized and their anti-influenza activity was screened. This review describes the rupestonic acid derivatives and their anti-influenza activity studied by our researching group.