Showing papers in "Mini-reviews in Medicinal Chemistry in 2013"

An Overview of the Modulatory Effects of Oleic Acid in Health and Disease

Abstract: 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.

The Universal Nature, Unequal Distribution and Antioxidant Functions of Melatonin and Its Derivatives

Abstract: Melatonin is an uncommonly widely distributed molecule. It is found throughout the plant and animal kingdoms, i.e., perhaps in every living organism. Within vertebrate organisms, melatonin also has an extremely wide distribution, seemingly being capable of entering every cell and all subcellular compartments. So-called morphophysiological barriers, e.g., the blood-brain barrier, are no impediment to the passage of melatonin and it has a multitude of confirmed functions. We have hypothesized that melatonin originally evolved as a free radical scavenger and during evolution it acquired other important and essential actions. Due to the multi-faceted actions of melatonin and its metabolites as direct free radical scavengers and indirect antioxidants, these agents have been used to abate oxidative damage in a diverse variety of experimental models where free radical destruction is a component. When compared with classic, better-known antioxidants, melatonin is better in terms of limiting destruction of intracellular macromolecules when the damage is a consequence of excessive oxygen or nitrogen-based toxic reactants. Considering the vast array of experimental data that has accumulated which documents melatonin's high efficacy and lack of, or minimal, toxicity over a very wide dose range, it is essential that the usefulness of this agent be more thoroughly tested at the clinical level. The findings from experimental models of numerous diseases overwhelming confirm that this indoleamine would likely have great benefit in aiding humans suffering with conditions that have as their basis tissue and molecular damage resulting from oxygen and nitrogen-based reactants.

The Antioxidant Activity of Coumarins and Flavonoids

Abstract: Coumarins and flavonoids are heterocyclic molecules that have been associated with beneficial effects on human health, such as reducing the risk of cancer, diabetes, cardiovascular and brain diseases. These effects are thought to be related to the radical scavenging effect, due to their antioxidant activities, along with other possible mechanisms, such as anti-inflammatory properties and interaction with several enzymes. Over the past two decades, there have been an increasing number of publications on coumarins and flavonoids, which demonstrate the importance of understanding the chemistry behind the antioxidant activities of both natural and synthesized compounds, considering the benefits from their dietary ingestion as well as pharmacological use. This work aims to review the antioxidant effects of coumarin and flavonoid molecules in humans and the structural aspects that contribute to these effects.

Nutritional and Medical Applications of Spirulina Microalgae

Abstract: Spirulina spp. and its processing products are employed in agriculture, food industry, pharmaceutics, perfumery and medicine. Spirulina has several pharmacological activities such as antimicrobial (including antiviral and antibacterial), anticancer, metalloprotective (prevention of heavy-metal poisoning against Cd, Pb, Fe, Hg), as well as immunostimulant and antioxidant effects due to its rich content of protein, polysaccharide, lipid, essential amino and fatty acids, dietary minerals and vitamins. This article serves as an overview, introducing the basic biochemical composition of this algae and moves to its medical applications. For each application the basic description of disease, mechanism of damage, particular content of Spirulina spp. for treatment, in vivo and/or in vitro usage, factors associated with therapeutic role, problems encountered and advantages are given.

Phenolic compounds as antioxidants: carbonic anhydrase isoenzymes inhibitors.

Abstract: Antioxidant compounds can scavenge free radicals and increase shelf life by retarding the process of lipid peroxidation, which is one of the major reasons for deterioration of food, medicine and pharmaceutical products during processing and storage. An antioxidant molecule has been defined as any substance when found in low concentrations compared to that of an oxidizable substrate significantly delays or inhibits the oxidation. The major antioxidant compounds are especially phenolics and flavonoids, which are responsible for their health benefits. Carbonic anhydrase (EC 4.2.1.1., CA) is a pH regulatory/metabolic enzyme in all life kingdoms, being found in organisms all over the phylogenetic tree. It catalyzes the hydration of carbon dioxide (CO(2)) to bicarbonate (HCO(3) -) and the corresponding dehydration of HCO(3) -in acidic medium with regeneration of CO(2). Also, CA isoforms are found in a variety of tissues where they participate in several important biological processes such as acid-base balance, respiration, carbon dioxide and ion transport, bone resorption, ureagenesis, gluconeogenesis, lipogenesis and electrolyte secretion. On the other hand, the phenyl moiety of phenol was found to lay in the hydrophobic part of the CA active site, where CO(2), the physiologic substrate of the CAs, binds in the precatalytic complex, explaining thus the behavior of phenol as a unique CO(2) competitive inhibitor. This review consists of two main sections. The first section is devoted to main phenolic antioxidant compounds in the foodstuffs and beverages. The second general section is about some definitions of CA inhibitory effects of the main phenolic compounds used for antioxidant activity. The phenolic compounds and acids had marked especially CA I and CA II inhibitory effects and might be used as leads for generating CA isoenzyme inhibitors. This class of compounds may lead to isoform-selective inhibitors targeting just one or few of the medicinally relevant CAs. In addition, there are given some chemical and kinetic basis and technical details related to phenolic antioxidant compounds and carbonic anhydrase isoenzymes.

Mangiferin - a bioactive xanthonoid, not only from mango and not just antioxidant.

Abstract: Mangiferin is a plant natural polyphenol of C-glycosylxanthone structure and various pharmacological activities. It can be found in many plant species, among which the mango tree (Mangifera indica) is one of the primary sources. Mangiferin is also present in some medicinal herbs, influencing their therapeutic and preventive properties, and in honeybush (Cyclopia sp.), a popular South African herbal tea. Mangiferin dissolves well in water, so it can be easily extracted into infusions and decoctions. In the mangiferin molecule, four aromatic hydroxyl groups determine its strong antiradical and antioxidant properties. Mangiferin is also an efficient iron chelator, therefore preventing the generation of hydroxyl radical in Fenton-type reactions. Numerous published in vitro and in vivo pharmacological studies, demonstrated many other activities of mangiferin: analgesic, antidiabetic, antisclerotic, atimicrobial and antiviral, cardio-, hepato-, and neuroprotective, antiinflammatory, antiallergic, MAO inhibiting and memory improving, as well as radioprotective against X-ray, gamma, and UV radiation. Several studies indicated also its ability to inhibit cancerogenesis and cancer cells growth by apoptosis induction in vitro and in vivo. It is also used in cosmetics, due to antioxidant and UV-protecting properties.

Pyrazolines: A Biological Review

Abstract: Pyrazoline is an important five membered nitrogen heterocycle, which has been extensively researched upon. The ring is quite stable and has inspired chemists to carry out various structural variations in the ring. This has propelled the development of distinct pyrazolines with an array of pharmacological activities viz. anti-inflammatory, analgesic, antimicrobial, anticancer, antidepressant etc. The review aims at highlighting this pharmacological diversity of pyrazolines. The review is a gist of latest work done describing the pharmacological aspects and potential of pyrazoline ring.

Chemistry and biology of indoles and indazoles: a mini-review.

Abstract: The present review article is related with the method of preparation, importance and medicinal application of indole and indazoles. The studies of heterocycles is an evergreen field in the branch of organic chemistry and always attract the attention of chemists working not only in the area of natural products but also in the synthetic chemistry. Moreover many useful drugs have emerged from the successful investigation carried out in this branch. The derivatives of indoles and indazoles exhibits antibacterial, anticancer, antionidants, anti-inflammatory, antidiabetic, antiviral, atniproliferative, antituberculosis, antispermetogenic activity, antipsychotic drugs etc.

An Evolving Role of Piperazine Moieties in Drug Design and Discovery

Abstract: This article purposes to provide insights to piperazine based molecular designs that will facilitate drug discovery program in future. In our pursuit to summarize the reservoir of bioactive agents, and in line with the synthetic economy of new heterocycles, many new roles are being identified for the multiple biotargets of piperazine moieties. We mark out how series of different scaffolds provide an extensive range of various piperazine-based analogues displaying antimicrobial, antituberculosis, anticancer, antiviral and antimalarial activities. We believe that piperazine family of compounds, and their various co-components, highlight the existence of several potential leads for the furtherance of novel bioactive agents.

Unequivocal role of pyrazine ring in medicinally important compounds: a review.

Abstract: Pyrazine is one of the important class of heterocyclic compounds that can be obtained naturally or synthesized chemically. Pyrazine ring has got importance in exhibiting various biological activities in association with other scaffolds like pyrrole, pyrazole, imidazole, triazole, tetrazole, thiophene, oxazole, pyridine, piperidine and piperazine. Presence of pyrazine ring as a basic scaffold in various clinically used drugs exhibits its importance in drug design. In this review, attempt has been made to disclose various therapeutic applications of pyrazine derivatives reported during the last decade.

Hydrazides/Hydrazones as Antimicrobial and Anticancer Agents in the New Millennium

Abstract: Hydrazide/hydrazone derivatives are of quite interest for medicinal chemists because of their vast spectrum of biological activity. Literature reports reveal that the hydrazide derivatives have been extensively studied for their biological profile during the past decade. The aim of the present work is to collect literature reports focusing the antimicrobial and anticancer study of different hydrazide/hydrazone derivatives carried out during the past decade which will serve as a valuable source of information for the researchers working in the field of antimicrobial and anticancer research.

Imidazoles as promising scaffolds for antibacterial activity: a review.

Abstract: In the last few decades, a lot of work has been done on heterocycles, especially the imidazole ring, to obtain a scaffold with potential pharmacological properties such as antibacterial, antifungal, anticancer, antiviral, antidiabetic and others, with lesser side effects. The search for new biologically active imidazoles continues to be an interesting area of investigation in medicinal chemistry. The present paper aims to bring together and discuss the wealth of information on antibacterial profile of imidazoles. So it can be employed for future development to obtain new potent drug molecules.

Alkaloids from piper: a review of its phytochemistry and pharmacology.

Abstract: 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.

Malaria and artemisinin derivatives: an updated review.

Abstract: Malaria is the world's most prevalent disease that affects 515-600 million people each year and about 40% of the world's population live at risk for this infection. The prevalence of morbidity and mortality from drug resistant malaria (Plasmodium falciparum) is increasing in most of the developing countries, which is also a global threat because international travel is common now and imported malaria is increasingly a serious problem. Since rapid schizonticidal action of naturally occurring endoperoxides pharmacophore present in artemisinin against drug-resistant malaria has been documented, researchers have focused more on artemisinin analogs than any other antimalarials. In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives (arteether, artemether, artemiside, artemisinin, artemisone, artesunate, dihydroartemisinin) have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.

Benzimidazole derivatives as potential anticancer agents.

Abstract: Benzimidazole ring system is found in many bioactive heterocyclic compounds because of their diverse biological and clinical applications. Furthermore, benzimidazole derivatives are structural isosters of naturally occurring nucleotides, thus they can interact with biological macromolecules such as proteins, enzymes and receptors. This review discusses the benzimidazole derivatives which possess anticancer activity of medicinal efficacy.

Imidazoles as potential antifungal agents: a review.

Abstract: Imidazoles are one of the most promising and vigorously pursued areas of contemporary antifungal chemotherapy depicting broad spectrum and potent activity. They have relatively simple molecular nucleus, which is amenable to many structural modifications. These agents have several favorable properties such as excellent bioavailability, good tissue penetrability and permeability and a relatively low incidence of adverse and toxic effects. They have been found effective in the treatment of various infectious diseases. This paper is an attempt to review the therapeutic potential of imidazoles as antifungal with an updated account on their development.

Novel Research Strategies of Benzimidazole Derivatives: A Review

Abstract: Benzimidazole plays an important role in the medicinal chemistry and drug discovery with many pharmacological activities which have made an indispensable anchor for discovery of novel therapeutic agents. Substitution of benzimidazole nucleus is an important synthetic strategy in the drug discovery process. Therapeutic properties of the benzimidazole related drugs have encouraged the medicinal chemists to synthesize novel therapeutic agents. Therefore, it is required to couple the latest information with the earliest information to understand the current status of benzimidazole nucleus in drug discovery. In the present review, benzimidazole derivatives with different pharmacological activities are described on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for the development of SAR on benzimidazoles for each activity. This article aims to review the work reported, chemistry and pharmacological activities of benzimidazole derivatives during past years.

Recent studies of antioxidant quinoline derivatives.

Abstract: Quinoline derivatives constitute an important class of compounds for new drug development. As a large number of experimental and theoretical studies have shown that the quinoline ring system is an important structural unit widely existing in alkaloids, therapeutics and synthetic analogues with exciting biological activities. The present review provides recent antioxidant activities covering in vivo and in vitro studies of natural and synthetic analogues, as well as the proposed mechanisms of action and structure-activity relationships.

Chitin synthase inhibitors as antifungal agents.

Abstract: 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.

Palmitoylethanolamide is a new possible pharmacological treatment for the inflammation associated with trauma.

Abstract: 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.

Pyrazole Derivatives as Antitumor, Anti-Inflammatory and Antibacterial Agents

Abstract: Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

Adhesion of osteoblasts to a vertically aligned TiO2 nanotube surface.

Abstract: 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.

Ghrelin in Obesity, Physiological and Pharmacological Considerations

Abstract: The aim of this review is to summarize the physiological and pharmacological aspects of ghrelin. Obesity can be defined as an excess of body fat and is associated with significant disturbances in metabolic and endocrine function. Obesity has become a worldwide epidemic. In obesity there is a decreased growth hormone (GH) secretion, and the altered somatotroph secretion in obesity is functional. Ghrelin is a peptide that has a unique structure with 28 amino-acids and an n-octanoyl ester at its third serine residue, which is essential for its potent stimulatory activity on somatotroph secretion. The pathophysiological mechanism responsible for GH hyposecretion in obesity is probably multifactorial, and there is probably a defect in ghrelin secretion. Ghrelin is the only known circulating orexigenic factor, and has been found to be reduced in obese humans. Ghrelin levels in blood decrease during periods of feeding. Due to its orexigenic and metabolic effects, ghrelin has a potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal and cardiac disease, and age-related frailty. Theoretically ghrelin receptor antagonists could be employed as anti-obesity drugs, blocking the orexigenic signal. By blocking the constitutive receptor activity, inverse agonists of the ghrelin receptor may lower the set-point for hunger, and could be used for the treatment of obesity. In summary, ghrelin secretion is reduced in obesity, and could be partly responsible for GH hyposecretion in obesity, ghrelin antagonist or partial inverse agonists should be considered for the treatment of obesity.

Phenolic compounds: the role of redox regulation in neurodegenerative disease and cancer.

Abstract: Much work has been carried out in the last two decades on the role of oxidative stress and antioxidants deficiency in the pathophysiology of civilization diseases. A considerable amount of chemical, biochemical, epidemiological and clinical evidence indicates that (poly)phenolic compounds widely distributed in the plant kingdom, exhibit a wide range effects on biomolecules. The beneficial effects on human health, many of phenolics have been described to their reactive oxygen (ROS) and nitrogen species (RNS) scavenging and antioxidant capacity. The consumption of vegetables, fruits and flavonoid-rich beverages has been reported to prevent against neurodegenerative diseases, cancer, and ageing. This paper reviews the recent data on (1) the role oxidative stress in the pathology of civilization diseases; (2) the protection against oxidative damage due to the toxicity of ROS/RNS; (3) the cellular and molecular interactions of the (poly)phenolic compounds relevant to the prevention of neurodegenerative diseases and cancer, and (4) the methods for assessing antioxidant capacity.

Haloperidol Cytotoxicity and Its Relation to Oxidative Stress

Abstract: Haloperidol (HP) is used for the symptomatic treatment of psychosis, manic phases, hyperactivity, aggressiveness, and acute delirium. Long-term use leads to various adverse side effects, especially to severe impairment of extrapyramidal nerve tracts and in particular, altered QT interval and increased incidence of arrhytmias. It is believed that cytotoxicity of HP and its metabolites is responsible for both neurotoxicity and cardiotoxicity. Extrapyramidal and cardiac adverse side effects may be explained by the HP-induced oxidative stress, as implicated by many studies. HP was reported to induce lipid peroxidation with subsequent membrane changes, responsible for cell death. Vice versa, cells resistant to oxidative stress are also resistant to the toxic effects of HP. Similarly, high percentage of patients suffering from extrapyramidal symptoms treated by vitamin E and other lipid-soluble antioxidants demonstrates diminishing of these adverse side effects. HP’s ability to induce oxidative stress by multi-modal action (increased metabolism of dopamine, decrease of glutathione content, induction of NF-B transcription factor, and inhibition of complex I of respiratory chain) has been established just recently. This review brings summarizing view on the cytotoxicity of haloperidol and involvement of reactive oxygen species and oxidative stress HP-induced cytotoxicity.

Niche for Acridine Derivatives in Anticancer Therapy

Abstract: During the last 4 decades, intensive research has focussed on the effect of small organic molecules with antitumour activity that are able to intercalate into DNA and inhibit topoisomerase and telomerase enzymes. In this review, we describe some of the chemical and biological properties of acridine, which is a chemotherapeutic agent that has been used for cancer treatment since 1970. In addition, we summarise the progress that has been made in the development of anticancer agents based on the clinical in vivo/in vitro studies that have been conducted for 13 classes of natural and synthetic acridines.

Saponins: the Potential Chemotherapeutic Agents in Pursuing New Anti-glioblastoma Drugs

Abstract: Saponins are natural glycosides consisting of a triterpene or steroid aglycone with a range of pharmacological properties such as significant anti-tumor activity. In this article, we review our recent progress in the studies of the saponins possessing anticancer effects, especially anti-glioblastoma effects from twelve species of marine organisms and terrestrial plants. The anti-glioblastoma active saponins discovered by other researchers in recent decades are also reviewed and compared. Systematic extraction, isolation and structural elucidation on the saponin constituents from three species of starfishes, five species of sea cucumbers and four species of medicinal plants led to the identification of more than 129 saponins, among which 76 saponins are new compounds. Most of the new compounds were found to possess relatively rare structural features showing in vitro cytotoxicity against tumor cells, especially glioblastoma cells. Several saponins exhibited significant anti-glioblastoma effects in vivo by in situ administration (interstitial chemotherapy) and their haemolytic side effects were avoided in the tests. Multiple mechanisms of action, such as interfering with cell cycle progression, inducing apoptosis, promoting stabilization of microtubule, as well as several signal transduction pathways, were involved in their anticancer effects. The review provided valuable leads for pursuing new anti-glioblastoma drugs, and established a new viewpoint for further development of these marine and terrestrial organisms. The successful approach to administrate saponins in situ conquered the bottleneck in the development of saponins as new drugs- haemolytic effects. It means that saponins may be developed as potential chemotherapeutic agents in pursuing new antiglioblastoma drugs.

The properties and the use of substituted benzofuroxans in pharmaceutical and medicinal chemistry: a comprehensive review.

Abstract: Since the synthesis of 4,6-dinitrobenzofuroxan in 1899 by Drost, benzofuroxans have attracted particular attention. This peculiar series of compounds exhibit a broad spectrum of biological activity including antibacterial, antifungal, antileukemic, acaricide and immunodepressive properties. These works embrace a period of more than 50 years since the pioneering paper of Gosh and Whitehouse and papers in this major field of the heterocyclic chemistry are still published in 2013. The review has been built in two independent parts. The first one is directly dedicated to the structure of substituted benzofuroxans and will show many medicinal applications of these compounds such as nitric oxide-releasing abilities, induction of oxidative stress, potent anti-cancer agents, anti-chagas agent, target for antiamoebic agent, Ca2+ channel blockers or cytotoxic, mutagenic and genotoxic agent… The second part of this review will be in close connection with the use of benzofuroxans as synthetic precursors in the preparation of new biological compounds such as quinoxaline dioxide, benzimidazole and phenazine derivatives. The interaction of substituted benzofuroxans with electron rich heterocycles or carbanions is the key step in the synthesis of these new biological active compounds. These derivatives can be used as cytotoxic drugs, antimycobacterial agent and display anti-malarial, antileishmanial and antituberculosis activity. The nature of the substituent linked to the carbocyclic ring of benzofuroxan is of primary importance to understand the medicinal properties of this family of compounds. For example, when benzofuroxans are substituted by electron-releasing substituents, the chemical reactivity is transferred from the carbocyclic ring to the furoxan ring.

Quinolines as Chemotherapeutic Agents for Leishmaniasis

Abstract: The development of leishmanicidal quinolines and their in vitro (promastigote and amastigote) and, where applicable, in vivo activities are reviewed. This survey provides a direct comparison of bioactivity across different species(e.g. L. donovani, L. amazonensis, L. chagasi, L infantum), and in different animal models (e.g. L. donovani Balb/c mice and L. donovani infected hamsters). The progress of selected quinolines through pre-clinical development and phase I/II trials, and the lead quinoline drugs sitamaquinine and Imiquimod, are discussed in conjunction with delivery systems and combination therapies.

Antibody-Targeted Immunoliposomes for Cancer Treatment

Abstract: Monoclonal antibodies (mAbs) or their derivatives are often used as the targeted ligands in the ligand targeted liposomes (LTLs). LTLs modified with mAbs or their derivatives are defined as immunoliposomes. Immunoliposomes can be designed to improve the pharmacological properties of conventional drugs. The development of immunoliposomes, which perfectly combines antibody engineering and liposomes, is becoming a possible state-of-the-art in liposome research. This review discusses the recent characterization and therapeutic effects of immunoliposomes in cancer therapy. The recent advances in the field of immunoliposomes for the treatment of cancer are summarized as follows: antibody engineering, current antibody conjugation strategies, characterization and therapeutic effects of immunoliposomes and the future perspective of immunoliposomes. Although antibody targeted immunoliposomes are being developed rapidly, there has been still a number of hot spots in research that require sustained effort for success. It is reasonable to predict that immunoliposomes will be approved for clinic use, and patients will benefit much from this cancer targeted therapy.