Book Volume 4
Page: i-i (1)
Page: ii-iii (2)
Page: 1-40 (40)
Author: Neelam Bharti, Prabhu P. Mohapatra and Shailendra Singh
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Amoebiasis, caused by Entamoeba histolytica (E. histolytica), is the third leading cause of health problems in developing countries and affects more than 10% of the world’s population. If left untreated, amoebiasis causes severe complications including hepatic and intestinal tissue destruction. According to World Health Organization (WHO), approximately 80% of the people in less-developed countries still rely on traditional medicine for their healthcare needs. In different parts of the world, plant extracts obtained from numerous plants have been used in the indigenous system of medicine for the treatment of dysentery. To apply these remedies to the rational scientific use of herbal medicines, studies on antiamoebic drugs mainly focused on natural products associated with folklore medicine. Plant extracts have been tested, and several natural products have been isolated from the active fractions, leading to the characterization and extensive biological studies of the isolated compounds. This book chapter reviews the noticeable crude extracts from medicinal plants tested for antiamoebic activities and isolated natural products that have been evaluated for antiamoebic activities in the last five decades. Most of these compounds with known structures belong to alkaloids, terpenoids, quassinoids, flavonoids, iridoids, and other phenolic compounds obtained from higher plants. These natural products showed activity against E. histolytica and other protozoa in vitro, and some of the natural products have been tested in vivo. Only a very few of them have been tested clinically. Herein, we report the traditional user’s knowledge, pharmacological activity, mechanism of action, toxicity, and other properties of antiamoebic natural products.
Page: 41-90 (50)
Author: Rita Turnaturi, Lorella Pasquinucci and Carmela Parenti
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The use of natural products as traditional medicines, remedies, potions and oils have been described since ancient times for the treatment of many diseases. Plant derived natural products, in particular, represent a successful source for potential drug leads. For instance, morphine, a mu opioid peptide receptor (MOPr) agonist, clinically used as analgesic, is an alkaloid isolated from opium poppy of Papaver somniferum. After its isolation, ongoing efforts in medicinal chemistry opened a wide program of research aimed to discover analogues that maintain the analgesic profile of morphine but reduced side effects. Analogously, mitragynine, an alkaloid isolated from the Thai medicinal plant Mitragyna speciosa, showed morphine-like properties in pain animal models although its chemical structure is different from that of morphine. Mitragynine has analgesic, muscle relaxant, anti-inflammatory, anorexic effects and, similarly to morphine, leads to tolerance and aversive withdrawal effects if chronically administered. Mitragynine actions involve MOPr, neuronal Ca2+ channels and monoaminergic system. Salvinorin A, extracted from Salvia divinorum, was used by Indian tribes of southern California as an aid in childbirth. It is a kappa opioid peptide receptor (KOPr) agonist with anti-addictive properties identified as a potential treatment for drug abuse. In this chapter Salvinorin A and Mitragynine pharmacological and chemical features, that made them suitable scaffolds for medicinal chemistry approaches, are described. Our efforts are focused on the description of SAR (structure-activity relationship) of salvinorin A and mitragynine derivatives developed to obtain a reduced burden of undesirable effects.
Page: 91-118 (28)
Author: Snezana Agatonovic-Kustrin and David W. Morton
Plant remedies and essential oils have been used throughout history for medicinal purposes in treating physiological and psychological health conditions. However, there is limited clinical evidence to show they are effective. However, a few clinical studies show they are a safe and effective treatment for mental illness, as an aid in cognitive function, agitation, memory enhancement and mood, but further research is needed. Aromatherapy, a process using essential oils to heal, may be viewed as archaic by society, but modern researchers have found that it can be quintessential in the fight against various types of dementias. Aromatherapy with plant essential oils, mostly from the Mint family, can significantly reduce the agitated behaviors seen in Alzheimer’s disease (AD) patients and improve cognitive function. Although there is an olfactory dysfunction in people with AD, the loss of smell does not affect the effectiveness of the essential oils. Therefore, their active components must be able to be absorbed via skin or respiration, cross the blood brain barrier, and produce systemic effects. The major active components of these essential oils, terpenes like 1,8-cineole have been correlated with positive cognitive performance. However, 1,8-cineole, is found in other plants, like eucalyptus, whose essential oils do not have memory enhancing effects. Thus, it’s possible that detected blood levels for 1,8-cineole simply work as a marker for relative levels of other active components that are present in much smaller quantities in therapeutic essential oils.
Page: 119-155 (37)
Author: Bruno M. Fonseca, Georgina Correia-da-Silva and Natercia Teixeira
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Phytocannabinoids as other natural products have been used as medicine for millennia. Although the advent of molecular biology and combinatorial chemistry reduced the use of natural products in drug discovery, nature continues to influence the design of new drug candidates. Cannabis sativa plant and its phytochemical products (hashish, marihuana) contain more than 100 cannabinoid compounds establishing an important family of complex chemical molecules that exert most of their actions by binding to and activating specific cannabinoid receptors (CB1 and CB2). The identification of cannabinoid receptors has led to discovery of the endogenous ligands termed endocannabinoids (eCBs). Cannabinoid receptors, the eCBs and respective metabolic enzymes comprise an important endogenous system, called endocannabinoid system (ECS), which is widely distributed in the body and is considered to be responsible for the regulation of various pathophysiological functions. This makes ECS a remarkable therapeutic promise in a variety of pathological conditions and supported the regulatory approval of several cannabinoid molecules of natural and/or synthetic origin. This emergent interest in cannabinoid properties has been accompanied by a growth in the number of derived drugs in pharmaceutical development, with the most actively pursued therapeutic targets being pain, obesity, multiple sclerosis, and epilepsy.
Page: 156-203 (48)
Author: Maria Luisa Soares da Silva
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Lectins are proteins or glycoproteins present in a variety of natural organisms. Since the time they were first described, at the end of the nineteenth century, new methods for their extraction and purification have been developed and, in parallel, they have been thoroughly studied. In spite of their great diversity and ubiquity, currently they constitute a group of well-characterized biomolecules. The most attractive feature of lectins is that they recognize and selectively bind to carbohydrate structures and that can be used for particular purposes in the biological and medical areas, for example. Due to their behaviour, lectins have become valuable analytical tools and numerous applications have been reported. Lectin-based analytical techniques allow to detect, extract, characterize and quantify specific glycans or glycoconjugates in diverse samples such as biological fluids. Glycobiology has benefit from this trend and lectins are present in some of the most promising applications, namely the diagnosis and monitoring of several diseases through the detection of their specific glycobiomarkers. One of the most prolific areas is the development of lectin-based biosensors for cancer biomarkers. Some limitations of lectins impair a wider application of these biomolecules as analytical tools, namely the lack of 100% specificity between a lectin and a glycan, in opposition to the unique and exclusive relation between an antigen and the corresponding antibody. This drawback can be problematic in the analysis of complex samples. Future directions may focus on identifying new and more specific carbohydrate ligands or developing multi-lectin tools in which a glycoprofile and not a single glycostructure is monitored.
Page: 204-239 (36)
Author: Indu Sharma, Renu Bhardwaj, Vandana Gautam, Ravdeep Kaur and Ashutosh Sharma
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Brassinosteroids (BRs) are a group of naturally occurring endogenous steroidal plant growth regulators (PGRs) which are hydroxylated derivatives of a 5α- cholestane ring structure. Both spectroscopy and X-ray based structural elucidation methods have revealed the structure of the first discovered BR, i.e. Brassinolide (BL) as (22R, 23R, 24S) - 2α,3α,22,23-tetrahydroxy-24-methyl-B-homo-7-oxa-5α- cholestan-6-one. Generally, the natural BRs are hydroxylated at the C-2, C-3, C-22 and C-23 positions. The most biologically active BRs differ from other BRs solely on the basis of either a 6-oxo functional group or a lactone structure at one of its rings. Presently, more than 60 types of BRs have been identified and isolated from a diverse range of plants. Recently, BRs have emerged as important PGRs that are a pre-requisite for growth and various developmental processes along with other PGRs namely auxins, gibberellins, cytokinins, ethylene and abscisic acid. Further, these BRs also provide protection to the plants under both biotic and abiotic stresses. Therefore, the present chapter highlights the structure, occurrence, mode of action, biosynthetic pathway, plant stress ameliorating properties of BRs and their interactions with other PGRs.
Page: 240-283 (44)
Author: Samir Mehndiratta, Mantosh Kumar Satapathy, Suhani Mankotia and Kunal Nepali
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Natural compounds, mostly from plants, are a potential source of antimalarial drugs due to presence of various secondary metabolites with variety of structures and different biological activities. Amongst the secondary plant metabolites, quassinoids, sesquiterpene lactone and alkaloids are the most important metabolites with diverse bio-potencies. Therefore, due to the wide use of alkaloid derived drugs, antimalarials can be grouped into two groups: alkaloidal antimalarials and nonalkaloidal antimalarials. By virtue of their chemical structure, the alkaloidal antimalarials are further classified into various classes (Bisbenzylisoquinolines, azaanthracene alkaloids, protoberberine and aporphine-benzylisoquinolines, morphinan alkaloids, naphthylisoquinolines, indoloquinolone alkaloids, indole alkaloids, benzofenantridine, furoquinolines and acridone, tetrahydroquinolines etc.). Apart from the bio-potency of the alkaloids, some other chemical entities (non-alkaloidal) show marked antimalarial activity which includes tannins, quassinoids, sesquiterpene lactones, limonoids, flavonoids, chromones, xanthones, quinones and other miscellaneous phenolic compounds and related compounds. This compilation covers most of recently published alkaloidal and non-alkaloidal antimalarial natural compounds with antiplasmodial and antimalarial properties published over last two decades. The structure, chemistry and evaluation of antimalarial activity of the compounds by in vitro and in vivo assays have been highlighted. Several patents published focusing on the phenyacetonitrile, bisquinoline, 4-amino quinoline, spiro and dispiro-1,2,4- trioxolane, phenyl(thio)urea deoxythymidine moieties as potent antimalarials have also been discussed in the current study. Besides, this review article also compiles the promising antimalarial compounds patented during the last two decades.
Page: 284-294 (11)
Frontiers in Natural Product Chemistry is a book series devoted to publishing monographs that highlight important advances in natural product chemistry. The series covers all aspects of research in the chemistry and biochemistry of naturally occurring compounds, including research on natural substances derived from plants, microbes and animals. Reviews of structure elucidation, biological activity, organic and experimental synthesis of natural products as well as developments of new methods are also included in the series. The fourth volume of the series brings seven reviews covering these topics: -natural antiamoebic medicines, analgesics and antimalarials -essential oils and cognitive performance -cannabis and drug development -lectins in biosensors -brassinosteroids