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β-amino acids are an important class of macromolecules. They play role in life for survival. β-amino acids gained significant interest due to their interesting pharmaceutical uses as hypoglycemic, antiketogenic characteristics, sterile and antifungal activities, anthelminthic as well as potent insecticidal characteristics. These are vital building blocks for the preparation of pharmaceutical and agrochemical target molecules. These are utilized in development of drugs, bimolecular structure and molecular recognition. They are also important in treatment of different diseases which are viral to human health. They play important role in regulation of nutritional metabolism and immunity. It has also led to their wider adoption as intermediates in new drugs and has been a focus of considerable attention in medicinal chemistry. β-amino acids have found extensive applications as components of biologically active peptides and small molecule pharmaceuticals. Synthetic derivatives of biologically relevant peptides incorporating β-amino acids often display interesting pharmacological activity, with increased potency and enzymatic stability. β-peptides participate in arrangement of incredible stable auxiliary structures. This review summarizes recent developments about the different roles of β-amino acids in human biology and some implications in medicinal chemistry.

Seven new and two known ent-labdane diterpenoids have been isolated from a single plant specimen of Dodonaea viscosa ssp. spatulata, found in Tasmania, Australia. Prior to this study, only seven different labdane diterpenoids had been isolated from D. viscosa. The structures of the natural products were assigned via 1D and 2D NMR spectroscopy and other standard spectroscopic methods. The absolute configuration of three ent-labdane diterpenoids was determined by single-crystal X-ray crystallography of synthetic derivatives. Significantly, the results of this study suggest that the absolute configuration of some known labdane diterpenoids may have been misassigned.

Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1). CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS)-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs.

This chapter deals with the synthesis, structures, kinetics and reactivity, solution equilibria and various applications of metal complexes of amino acids and peptides, including the most important synthetic derivatives and analogues of the naturally occurring ligands. The survey of the literature c...

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.

This review provides information on the biological activities of chalcones (whether natural or synthetic derivatives) on different organisms, as well as an overview of the functions and possible new applications of these plant secondary metabolites on crop protection, as eco-friendly pesticides and weed control agents. Naturally occurring chalcones have been used in traditional medicine for many years; however, recent scientific advances have shown that these molecules have a broad range of biological activities in a variety of organisms. A review on the major sources of chalcones and the main molecular events involved in the modes of action of these natural products is achieved. Chalcones are molecules with a broad spectrum of biological activities, which are of great interest in agriculture to control weeds and unwanted pests. RESUMO Esta avaliação fornece informações sobre as atividades biológicas de chalconas (quer derivados naturais ou sintéticos) em diferentes organismos, bem como uma visão geral das funções e eventuais novas aplicações desses metabólitos secundários de plantas em proteção de cultivos e pesticidas orgânicos e para controlar as plantas daninhas. Durante muitos anos têm sido utilizadas na medicina tradicional chalconas de ocorrência natural; no entanto, os recentes avanços científicos têm mostrado que essas moléculas têm vasta gama de atividades biológicas em uma variedade de organismos. Este estudo permite ter uma ideia das principais fontes de chalconas e dos eventos moleculares envolvidos nos principais mecanismos de ação desses produtos naturais. As chalconas são moléculas com um largo espectro de atividade biológica, de grande interesse na agricultura para controlar plantas daninhas e pragas indesejadas.

La (±)-3,4-metilendioxipirovalerona (MDPV) y la (±)-3,4-metilenedioximetilcatinona (metilona) son algunos de los derivados sintéticos de catinonas más frecuentemente encontrados en productos que se comercializan como “sales de baño” y que hoy en día se emplean como drogas de abuso. Los reportes de casos fatales por consumo de estas sustancias aumentan cada día, y aunque existen algunos estudios farmacológicos y toxicológicos, no son claros los mecanismos de acción y los efectos causados por su consumo recreativo. La implementación de sistemas que permitan conocer el metabolismo de estas drogas en humanos y el diseño de métodos analíticos para su detección son ahora objeto de investigación. Este artículo presenta una revisión bibliográfica acerca de los estudios de biotransformación para MDPV y metilona empleando modelos in vitro con microsomas hepáticos humanos, fracciones celulares S9 y modelos in vivo con animales de experimentación y posterior análisis de los metabolitos que hay hasta la fecha. Las técnicas analíticas utilizadas para el análisis de metabolitos incluyen cromatografía líquida acoplada a detector selectivo de masas (LC-MS o LC-MS/MS) o la formación de derivados acetilados o sililados para su posterior análisis por cromatografía de gases acoplada a detector selectivo de masas (GC-MS). Además, se incluye una propuesta para el estudio del metabolismo para metilona y MDPV a través de hongos del género Cunninghamella. (±)-3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylendioxymethylcathi-none (methylone) are some of the most frequent synthetic derivatives of cathinones found in commercial products known as "Bath salts" and which today are used as drugs of abuse. Reports on fatal cases involving the consumption of these substances are raising and although there are some pharmacological and toxicological studies, their action mechanisms and effects due recreational consumption are not very well understood. The implementation of systems that allows the understanding of the metabolism of these drugs in humans and the design of analytical methods for their detection is now the subject of research. This paper shows a bibliographical review of the studies conducted on the biotransformation of methylone and MDPV using in vitro models with human hepatic microsomes, cell fractions S9 and in vivo models in animals with posterior analysis of the obtained metabolites. The analytical techniques used for the analysis of the metabolites include liquid chromatography coupled with mass spectrometry (LC-MS or LC-MS/MS) or the formation of acetylated or dimethyl silylated derivatives for their posterior analysis by gas chromatography (GC-MS). A proposal for the study of the metabolisms of methylone and MDPV through the fungus of the genera Cunninghamella is also included.

There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states. We also provide a brief synopsis of selective androgen receptor modulators (SARMs) and postulate how these orally active, non-aromatizing, tissue-selective agents might be used in contemporary andrology. Currently, the applications of testosterone alternatives in hypogonadism are limited. However, it is tempting to speculate that these agents may one day become accepted as alternatives, or adjuncts, to the treatment of male hypogonadism.

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

Tetramethylpyrazine, a natural compound fromLigusticum wallichii(Chuan Xiong), has been extensively used in China for cardiovascular and cerebrovascular diseases for about 40 years. Because of its effectiveness in multisystems, especially in cardiovascular, its pharmacological action, clinical application, and the structural modification have attracted broad attention. In this paper its mechanisms of action, the clinical status, and synthetic derivatives will be reviewed briefly.

The number of synthetic derivatives of the world’s most popular and commonly abused drug, cannabis is rapidly growing dayby day. Although the drug has certain applications in the medical field, due to its wide and easy access and cheapness, more people start trying the drug commonly referred to as ‘Bonsai’. This synthetic form of the drug has many different names in different countries. The drug is most commonly referred as “Bonsai” in Turkey, “Spice” in UK and “K2” or “Jamaica” in the US. The synthetic cannabinoids are mainly smoked using a pipe, a hookah (or a bong), or wrapped in cigarette papers. Various cases, including the result of death, have been reported related to ‘Bonsai’ smoking. We present here a case of ‘Bonsai’ drug abuse with unusual presentation of paraplegia.

Background The generic name "flavonolignan" was created in 1968 for a relatively small class of naturally occurring hybrid molecules biogenetically originated from ubiquitous flavonoids and lignans (phenylpropanoids). The first group of flavonolignans was extracted from Silybum marianum that has long been used for hepatoprotection. Recently, the medicinal merit of flavonolignans has been extended to the prostate cancer management. Methods Systematic interpretation and summarization of the relevant literature. Results Over forty naturally occurring flavonolignans have so far been obtained from various plants. Certain flavonolignans have been demonstrated by in vitro cell-based and in vivo animal-based experiments, and human clinical studies i) to possess effective chemopreventive function against various tumor promoters; ii) to show the anti-angiogenic efficacy; iii) to have potential in treating prostate cancer; iv) to sensitize prostate tumors to chemotherapeutic agents through down-regulation of P-glycoprotein and other mechanisms; and v) to be used by prostate cancer patients to protect or treat the hepatotoxicity caused by several chemotherapies. Certain flavonolignans can synergize with well-established chemotherapeutic agents for prostate cancer. Conclusion This review provides a systematic and in-depth overview of the promise and potential of flavonolignans in prostate cancer management, which covers their chemopreventive effect, chemotherapeutic treatment, mechanisms of actions, synthetic derivatives, structure-activity relationships, and the difference in inhibiting prostate cancer cell proliferation between certain flavonoligans and their respective flavonoid counterpart. This summarization aims to provide valuable insights into further and rational development of flavonolignans for prostate cancer management by interpreting the data reported in the literature.

This paper presents a review on kaurane diterpenes, covering various aspects of chemical and microbiological transformations of native ent-kaurenoic acid, namely, its reactions via COOH groups, double bonds and rearrangements of the carbon skeleton that lead to a wide range of natural and synthetic derivatives with potential biologic activities and can present convenient synthons for the syntheses of other native ent-kauranes.

Liquid chromatography negative ion electrospray ionisation tandem mass spectrometry has been used for characterisation of naturally occurring prenylated fungal metabolites and synthetic derivatives. The fragmentation studies allow an elucidation of the decomposition pathways for these compounds. It could be shown, that the prenyl side chain is degraded by successive radical losses of C(5) units. Both the benzoquinones and the phenolic derivatives display significant key ions comprising the aromatic ring. In some cases, the formation of significant oxygen-free key ions could be evidenced by high-resolution MS/MS measurements. Furthermore, the different types of basic skeletons, benzoquinones and phenol type as well as cyclic prenylated compounds, can be differentiated by their MS/MS behaviour. Figure Fruiting bodies of Suillus bovinus, the structure of boviquinone-4 and its negative ion MS2 spectrum.

Gestagenic and contraceptive (in combination with estrogen) activities of megestrol acetate, proligestone, and two esters of mepregenol acetate (butyrate and hemisuccinate) were studied. The absence of a correlation between the gestagenic and contraceptive activity (CA) of the synthetic derivatives of 17α-hydroxyprogesterone was established. Of two compounds (proligestone and megestrol acetate) showing the maximum (100%) CA (in combination with ethynylestradiol), proligestone was practically devoid of gestagenic activity while megestrol acetate was a highly active gestagen. It was confirmed that the gestagenic activities of injected megestrol acetate and mepregenol acetate tended to exceed their peroral activities. Pure estrogen was found to contribute to the CA of the mepregenol esters.

The emergence of infections caused by multi-drug resistant (MDR) pathogens pose a major burden to modern healthcare. Exacerbating this issue is the substantial decline in development of new classes of antibiotics by pharmaceutical companies. This has led to renewed interest in the therapeutic potential of natural anti-infective agents such as host defense peptides (HDPs). The broad antimicrobial and immunomodulatory activities of HDPs and their synthetic derivatives, coupled with the fact that they do not readily induce microbial resistance, makes them extremely valuable leads in the development of new treatment strategies for MDR infections. This review examines our knowledge of the mechanisms behind multi-drug resistance as well as the properties of HDPs and their therapeutic potential, especially in the case of MDR infections. Challenges to their development as new therapeutics are also discussed.

Besides its particular importance as a widely used therapeutic agent, insulin (and its synthetic derivatives) has been suspected, purported, and proven to be a lethal weapon in numerous cases of attempted or successful homicide and suicide. In addition to blood and urine as common matrices for clinical diagnosis and post-mortem analysis, vitreous humour has gained considerable attention in autopsy and follow-up investigations due to its ability to provide valuable information on cause and time of death. However, post-mortem insulin analyses using such specimens have been rare due to the limited penetration of peptide hormones into the vitreous body, and immunoassays were exclusively employed in those studies. In the present communication, the determination of insulin(s) from vitreous humour by means of immunopurification combined with ultrahigh performance liquid chromatography--high resolution/high accuracy (tandem) mass spectrometry is reported. Exploiting the constantly increasing sensitivity and robustness of modern mass-spectrometry-based instruments, the option to identify insulin in post-mortem vitreous samples is demonstrated with a specimen collected from a non-diabetic victim who died from an insulin overdose. This communication represents the first successful mass-spectrometry-based analysis of post-mortem material related to an insulin poisoning case.

Contains fulltext : 97400.pdf (Publisher’s version ) (Closed access) Toll-like receptors (TLRs) recognise highly conserved molecular structures, collectively known as pathogen-associated molecular patterns. In the past two decades, development and clinical implementation of TLR ligands-ie, chemically modified synthetic derivatives of naturally occurring ligands and fully synthetic small molecules-have been topics of intense research. Targeted manipulation of TLR signalling has been applied clinically to boost vaccine effectiveness, promote a robust T helper 1-predominant immune response against viral infection, or dampen the exaggerated inflammatory response to bacterial infection. Use of these new therapeutic molecules as adjuncts to conventional pharmacotherapy or stand-alone treatments might offer solutions to unmet clinical needs or could replace existing partly effective therapeutic strategies.

Promising synthetic derivatives of macrolactone natural product (−)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (−)-A26771B with improved antibacterial activity and metabolic stability.

Although considerable progress in oncology therapeutics has been achieved in the last century, cancer remains one of major death causes in the World and for this reason, the development of novel cancer drugs remains a pressing need. Natural marine compounds represent an interesting source of novel leads with potent chemotherapeutic or chemo-preventive activities. In the last decades, structure-activity-relationship studies have led to the development of naturally-derived or semi-synthetic analogues with improved bioactivity, a simplified synthetic target or less toxicity. We aim here to review a selection of natural compounds with reported anticancer activity isolated of marine sources and their associated analogues published in 2010.

A series of new 11-aza-artemisinin derivatives were prepared from 11-aza-artemisinin using the Ugi reaction. An antimalarial activity evaluation against the FcB1 strain indicated that compounds 7, 10, and 16 had very strong inhibitory activity. Comparison of the activity among the synthetic derivatives of this series revealed that the length of the side chain R group on the amide nitrogen could be critical for their antimalarial properties.

Trans-resveratrol, the most well-known polyphenolic stilbenoid, is found in grapes and accordingly in wine and it is considered to be beneficial for human health, especially towards the aging-linked cell alterations by providing numerous biological activities, such as anti-oxidant, antitumoral, antiviral, anti-inflammatory, neuroprotective, and platelet anti-aggregation properties. Although trans-resveratrol is a promising molecule, it cannot be considered as a drug, due to its weak bio-availability and fast metabolism. To overcome these weaknesses, several research teams have undertaken the synthesis of innovative trans-resveratrol derivatives, with the aim to increase its solubility in water and pharmacological activities towards cell targets. The aim of this review is to show the chronological evolution over the last 25 years of different strategies to develop more efficient trans-resveratrol derivatives towards organism physiology and, therefore, to enhance various pharmacological activities. While the literature on the development of new synthetic derivatives is impressive, this review will focus on selected strategies regarding the substitution of trans-resveratrol phenyl rings, first with hydroxy, methoxy, and halogen groups, and next with functionalized substituents. The effects on cell functions and dysfunctions of interesting resveratrol analogs will be addressed in this review.

The antioxidant capacity of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles was evaluated. The values of antioxidant capacities of compounds 2d and 2e were found to be, respectively, 2,700 ± 150 and 3,135 ± 230 TE by the ORAC method, corresponding to a significant antioxidant capacity. recent publication, we reported the antioxidant capacity of phenylpyrazole using the ORAC method (14). In continua- tion of our research program, we report here the antioxidant evaluation of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4- phenylthiazoles, synthetic derivatives compounds of facile preparation (Scheme 1).

Physico-chemical and chemical properties of citric acid and methods of synthesis of its derivatives, namely esters, amides, 1,3-dioxolan-4-ones etc. are presented. The important group of natural derivatives of this acid belonging to the siderophore family, i.e. compounds fulfilling in nature the function of biocarriers of ferric ions, is described in detail. The recent advances in the total synthesis of natural siderophores — citric acid derivatives, its homologues and analogues of the “retro” type are summarized.

The use of drug substances derived from plants, fungi, bacteria, and marine organisms are “Mother Nature Gift” for diseases of mankind. Many of these are discovered serendipitously and have a long tradition in medicine. Till date, the use of natural products, their semisynthetic and synthetic derivatives have been mostly confined to their ethnic use. But it has been well known that each substance has a wide spectrum of biological activities as evident from some new uses of many old drugs. PASS (Prediction of Activity Spectra for Substances) has been employed as a strong potential tool to predict the biological activity spectrum of synthetic substances for the discovery of new drugs. But the potential of PASS to predict the biological activity spectra of natural products is still underestimated. The present study was therefore undertaken to investigate and correlate the biological activity spectrum of the main phytoconstituent of some selected Indian medicinal plants with their reported biological activities in order to evaluate the applicability of PASS. Further, the unexplored but PASS-predicted activities having good activity score (Pa > 0.7) for particular structure were listed as hidden potential of the plant.

A method of high performance liquid chromatographic separation of clausenamide enantiomers with chiral-AGP (α 1 -acid glycoprotein) stationary phases has been established. The absolute configurations of (−)clausenamide and (+)clausenamide are 3 S , 4 R , 5 R , 6 S and 3 R , 4 S , 5 S , 6 R , respectively. The present method has been used to analyze the (−)clausenamide and (+)clausenamide and its analogues such as the major metabolite and synthetic derivatives of clausenamide.

Individuals with epilepsy often complain about memory deficits. Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. Rutin is a flavonoid that is an important dietary constituent of foods and plant-based beverages. The aim of the present study was to investigate the effects of rutin on memory retrieval in pentylenetetrazole (PTZ)-kindled rats using a step-through passive avoidance task. We administered rutin and PTZ intraperitoneally every other day prior to the start of training. Two retention tests were subsequently performed to assess memory in these rats. The results suggest that pretreatment with rutin at 50 and 100mg/kg can attenuate seizure severity during the kindling procedure. Furthermore, rutin administration significantly increased the step-through latency in the passive avoidance paradigm. Taken together, these results indicate that rutin has a potential role in enhancing memory retrieval in kindled rats.

Cathinone is a pharmacologically active alkaloid that can be extracted from the leaves of the khat plant (Catha edulis). There are synthetic derivatives of cathinone entering the recreational drug market, including mephedrone (4-methylmethcathinone, 4-MMC). There are discrepancies in the legal status of both the khat plant and its extracted alkaloids between the UK and the USA.A 22-year-old man purchased 4 g of mephedrone powder over the Internet from a chemical supplier based in China. He initially ingested 200 mg of the mephedrone orally, with no perceived clinical effects, and thereafter injected the remaining 3.8 g intramuscularly into his thighs. Shortly after the injection, he developed palpitations, "blurred tunnel vision," chest pressure, and sweating and felt generally unwell; he presented to hospital with continuing features of sympathomimetic toxicity. His symptoms settled over the next 4 h after a single dose of oral lorazepam. Qualitative analysis of the urine and serum sample was undertaken using gas chromatography with mass spectrometric (GC/MS) detection, both positive for the presence of 4-methylmethcathinone. Quantitative analysis of the serum sample was undertaken by liquid chromatography with tandem mass spectrometric detection; the estimated mephedrone concentration was 0.15 mg/l. Routine toxicological analysis of the serum and urine specimens using a broad GC/MS toxicology screen did not detect any other drugs or alcohol.This is the first case of isolated 4-MMC toxicity, with confirmatory analytical findings. It is important that clinical toxicologists and emergency physicians work together to ensure a better understanding of the toxicity of novel/emerging drugs such as 4-MMC.

Sixteen new derivatives of spiromesifen were synthesized from 3-(2,4,6-trimethylphenyl)-4-hydroxy-Δ 3 -dihydrofuran-2-one. Their bioactivities against diamondbackmoth ( Plutella xylostella ) and spider mites ( Tetranychus cinnabarinus ) were also evaluated. The structures of these derivatives were confirmed by 1 H NMR, MS.

Whereas significant knowledge is accumulating on the antibacterial and antifungal properties of host defense peptides (HDPs) and their synthetic mimics, much less is known of their activities against parasites. A variety of in vitro and in vivo antiparasitic assays suggest that these notorious antimicrobial compounds could represent a powerful tool for the development of novel drugs to fight parasites in the vertebrate host or to complement current therapeutic strategies, albeit the fact that HDPs essentially act by nonspecific mechanisms casts serious doubt on their ability to exert sufficient selectivity to be considered ideal candidates for drug development. This minireview summarizes recent efforts to assess the antiparasitic properties of HDPs and their synthetic derivatives, focusing on two of the most used models –Plasmodium and Leishmania species – for antiparasitic assays against the different development stages.

Introduction in therapy of the naturally occurring trioxane artemisinin opened a new era in malaria treatment and prompted the development of semisynthetic and synthetic derivatives characterized by the presence of the key peroxide bridge. The 1,2-dioxane ring is present in some natural endoperoxides such as plakortin and dihydroplakortin, which are endowed with interesting antimalarial properties. Here we describe the development of a versatile stereocontrolled synthetic strategy to 1,2-dioxanes functionalized at the critical C3, C4, and C6 positions, potentially useful for the development of innovative antimalarials.

The present study aimed to evaluate the ability for biotransformation of the Diels-Alder adduct tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione (1) and two synthetic derivatives by the saprobe fungus Mucor ramosissimus Samutsevitsch. Products from oxidation, isomerization and, regioselective and enantioselective reduction were achieved. Neste trabalho avaliou-se a capacidade de biotransformação do aduto de Diels-Alder triciclo[6.2.1.02-7]undeca-4,9-dien-3,6-diona (1) e dois derivados sintéticos pelo fungo sapróbio Mucor ramosissimus Samutsevitsch. Produtos de oxidação, isomerização e redução regiosseletiva e enantiosseletiva foram obtidos.

Antimicrobial peptides have captured the attention of researchers in recent years because of their efficiency in fighting against pathogens. These peptides are found in nature and have been isolated from a wide range of organisms. Furthermore, analogs or synthetic derivatives have successfully been developed on the basis of natural peptide patterns. Long use of pesticides and antibiotics has led to development of resistance among pathogens and other pests as well as increase of environmental and health risks. Antimicrobial peptides are under consideration as new substitutes for conventional pesticides and antibiotics. Many plants and animals have been manipulated with antimicrobial peptide-encoding genes and several pesticides and drugs have been produced based on these peptides. Such strategies and products may still have a long way to go before being confirmed by regulatory bodies and others need to surmount technical problems before being accepted as applicable ones. In spite of these facts, several cases of successful use of antimicrobial peptides in agriculture and food industry indicate a promising future for extensive application of these peptides. In this review, we consider the developing field of antimicrobial peptide applications in various agricultural activities.

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

Aminoglycosides are antibiotics targeting the 16S RNA A site of the bacterial ribosome. There have been many efforts directed toward design of their synthetic derivatives, however with only few successes. As RNA binders, aminoglycosides are also a difficult target for computational drug design, since most of the existing methods were developed for protein ligands. Here, we present an approach that allows for evading the problems related to still poorly developed RNA docking and scoring algorithms. It is aimed at identification of new molecular scaffolds potentially binding to the A site. The considered molecules are based on the neamine core, which is common for all aminoglycosides and provides specificity toward the binding site, linked with diverse molecular fragments via its O5 or O6 oxygen atom. Suitable fragments are selected with the use of 3D searches of molecular fragments library against two distinct pharmacophores designed on the basis of available structural data for aminoglycoside-RNA complexes. The compounds resulting from fragments assembly with neamine are then scored with a 3D-QSAR model developed using the biological data for known aminoglycoside derivatives. Twenty-one new potential ligands are obtained, four of which have predicted activities comparable to less potent aminoglycoside antibiotics.

γ-L-Glutamyl derivatives and a β-L-aspartyl derivative of different amines (taurine, nortaurine, N-methyltaurine, taurine amide, tauryl-methylamine, tauryl-piperidine, β-alanine amide, orthanilic acid, 2-aminoethanephosphonic acid, ethanolamine-O-sulfate and ethanolamine-O-phosphate) have been synthesized by mixed anhydride or active ester coupling method. One of the dipeptide analogues, γ-L-glutamyl-(ethanolamine-O-sulfate) was prepared by esterification, too. Syntheses of α,γ-L-glutamyl-bis-taurine and of DL-2-amino-8-sulfo-octanoic acid are also described.

Compounds of polyketide origin possess a wealth of pharmacological effects, including antibacterial, anti-fungal, antiparasitic, anticancer and immunosuppressive activities. Many of these compounds and their semi- synthetic derivatives are used today in the clinic. Most of the gene clusters encoding commercially important drugs have also been cloned and sequenced and their biosynthetic mechanisms studied in great detail. The area of biosynthetic engineering of the enzymes involved in polyketide biosynthesis has recently advanced and been transferred into the industrial arena. In this work, we introduce a computational system to provide the user with a wealth of information that can be utilized for biosynthetic engineering of enzymes involved in post- PKS tailoring steps. Post-PKS tailoring steps are neces-sary to add functional groups essential for the biological activity and are therefore important in polyketide biosyn-thesis.Availability: The trial version of this system is available via WWW at http://sm.hacklib.com/.Keywords: pharmacological effects, gene clusters, bio-synthetic engineering, post-PKS tailoring step

Eugenol is found in essential oils of many plants. It belongs to a class of naturally occurring phenolic monoterpenoids, chemically it is an allyl chain-substituted guaiacol. Eugenol is a member of the phenylpropanoids class and is remarkably versatile molecule incorporated as a functional ingredient in several products and has found applications in the pharmaceutical, agricultural, fragrance, flavor, cosmetic and various other industries. Its vast range of pharmacological activities has been well-researched which include antimicrobial, anti-inflammatory, analgesic, antioxidant and anticancer activities. In present review we shortly summarize medicinal properties of Eugenol and its derivatives.

The phenanthridinone heterocyclic system has attracted considerable attention in recent years due to the diverse array of physical, chemical and pharmacological properties demonstrated by natural and synthetic derivatives. As a consequence there has been considerable development of synthetic methodology for the synthesis of this and related heterocyclic ring systems. The synthetic literature is discussed and is compared with a direct arylation methodology for the intramolecular cyclization of tertiary (2-iodo)benzoylamides to generate the biaryl bond of these compounds. The efficient methodology allowed the synthesis of a number of previously unknown phenanthridinone products. The photoluminescent properties of representative examples were characterized and it is proposed that the previously unknown compound 1s reveals dual fluorescence in a manner similar to the known compound 1r.

We herein described the preparation of a novel series of limonin derivatives (modification in A-ring), which was synthesized efficiently using methodology in solution as well as in heterogeneous medium (K-10). In addition, we obtained derivatives by inserting the 1,2,3-triazole nucleus via click reaction and also prepared derivatives from reactions with limonin-7-oxime. All compounds were submitted to investigation of the antimicrobial activity against a collection of microorganisms. The results of the antimicrobial activity, in general, demonstrated that a relevant number of synthetic derivatives presented higher activity than the natural product.

Inflammation is the primary host defense mechanism against all forms of injury. Excessive or inadequate activation of the system can have serious effects, as can the failure of inactivation mechanisms. Coumarins can reduce tissue edema and inflammation and inhibit prostaglandin biosynthesis, which involves fatty acid hydroperoxy intermediates. It is to be expected that coumarins might affect the formation and scavenging of reactive substances derived from oxygen species (ROS) and influence processes involving free radical-mediated injury, as can flavonoids. During these years a small number of (Q)SAR studies concerning coumarins as NSAIDs has been presented and reviewed. In this research we tried to examine the structure-function relationship for coumarins, presenting antiinflammatory activity. Coumarin (1), the prototypical compound presents anti-inflammatory activity. The hydroxylaromatic substituted derivatives (5- or 6- or 7-hydroxy or the vicinal dihydroxy) seems to be potent inhibitors of lipoxygenase. Several synthetic derivatives simple or more complicated were found to be potent antiinflammatories/antioxidant agents.

Artemisinin and its synthetic derivatives are widely used for antimalarial agents in the world. Moreover, they are discovered to additionally use as anticancer, antiangiogenesis, antiviral, immunosuppressive, and antifungal agents. Recent research results supported that it is a very promising field in drug discovery. In this review, it will discuss the structural and biological features of artemisinin and its derivatives that have published since 2003 except antimalarial, and show that they are useful lead compounds for novel drug discovery.

The need for safe, therapeutically effective and patient-compliant drug delivery systems continuously leads researchers to design novel tools and strategies. Clay minerals are widely used materials in drug products both as excipients and active agents. When administered simultaneously, drug–clay interactions have been observed and studied, but until recently were not considered as a possible mechanism to modify drug release. In recent years, and based on their high retention capacities as well as swelling and colloidal properties, clays have been proposed as very useful materials for modulating drug delivery. This paper first reviews the studies on drug–clay interactions, and then those focused on the applications of natural clays and their semi-synthetic or synthetic derivatives to carry out specific functions in new drug delivery systems. In particular, clays are used to delay and/or target drug release or even improve drug dissolution. Finally, new strategies are reported for increasing drug stability and simultaneously modifying drug delivery patterns through the use of clay minerals.

Malaria is one of the most severe tropical parasitic disease causing 1-3 million deaths annually. In the last 25 years very few new antimalarial molecules have been developed and only a limited number of them are currently in various stages of clinical development. The presently available antimalarial drugs include artemisinin analogs, quinoline derivatives and antifolates. This review summarizes recent advances in antimalarial drug development and world patents published between 2000-2006 claiming new synthetic antimalarial compounds and their activities. The most over-represented classes of compounds in malaria patent literature in order of frequency are artemisinin analogs, quinoline derivatives, DOXP reductoisomerase inhibitors, antifolates and febrifugine analogues. Many of these patents describe the novelty and potential of these synthetic derivatives with an attempt to identify the next generation antimalarials that may have potential commercial advantages.

Five isoliquiritigenin analogues, including a new methylene-bridged bischalcone (1), were isolated from Spatholobus suberectus. Cytotoxicity screening of these isolates and several synthetic derivatives indicated that the introduction, removal, position modification, or glycosylation of hydroxy groups in isoliquiritigenin did not improve the resultant cytotoxicity against the MCF-7 and MDA-MB-231 human breast cancer cell lines. In addition, cyclization of OH-2' chalcones or reduction of the α,β-unsaturated carbonyl double bond decreased such cytotoxicity substantially. However, methylation of hydroxy groups resulted in a marked increase in such cytotoxic activity. Among these active isoliquiritigenin analogues, 3',4',5',4″-tetramethoxychalcone (3h) was obtained as a compound with promising cytotoxic activity.

Background Since its isolation in 1970, and discovery of its potent inhibitory activity on T-cell proliferation, cyclosporin A (CsA) has been shown to play a significant role in diverse fields of biology. Furthermore, chemical modification of CsA has led to analogs with distinct biological activities associated with its protein receptor family, cyclophilins. Scope of review This review systematically collates the synthetic chemistry performed at each of the eleven amino acids, and provides examples of the utility of such transformations. The various modifications of CsA are traced from early, modest chemistry performed at the unique Bmt residue, through the remarkable use of a polyanion enolate that can be stereoselectively manipulated, and onto application of more recently developed olefin metathesis chemistry to prepare new CsA derivatives with unexpected biological activity. Major conclusions The myriad biological activities of CsA and its synthetic derivatives have inspired the development of new approaches to modify the CsA ring. In turn, these new CsA derivatives have served as tools in the discovery of new roles for cyclophilins. General significance This review provides information on the types of cyclosporin derivatives that are available to the many biologists working in this field, and should be of value to the medicinal chemist trying to discover drugs based on CsA. This article is part of a Special Issue entitled Proline-directed foldases: Cell signaling catalysts and drug targets.

Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical – and difficult - stage in the discovery pipeline. Of all the factors to be considered, perhaps the most important, is that the compound should have the desired effect on the tissue in vivo. Since it is not possible (or ethical) to test all compounds in vivo one must preselect using a surrogate assay system. While animal models have the advantage of being holistic and current 3D culture systems are reductionistic, they at least can be constructed from human cell types.In this review we will consider some of the evidence demonstrating that cells grown in 3D cultures have physiological performances that mimic functions seen in human tissues significantly better than cells grown using classical 2D culture systems. We will discuss advantages and disadvantages of these new culture technologies and highlight theoretical reasons for the differences.3D cell culture technologies are more labour intensive than 2D culture systems and therefore their introduction is a trade-off between the value of obtaining data that is more relevant to the human condition against their through-put. It is already clear that future in vitro 3D systems will become more complex, using multiple cell types to more faithfully represent a particular tissue or even organ system. And one thing is sure – the diamonds are not easy to find!