Current Organic Chemistry - Volume 21, Issue 18, 2017

Background: Avian influenza, commonly known as bird flu, is caused by viruses adapted to birds; however, some of the avian viruses are highly pathogenic to the human population. Though vaccines have been developed for the prevention of avian influenza, the emerging resistant strains greatly limit the effectiveness of these mainstay prophylactic drugs. Thus, novel anti-avian influenza agents are sought for the dissemination of such resistance crisis. Plants in great biological diversities stand as infinite resources for the development of novel anti-influenza agents. Objective & Method: In this article, a comprehensive review of the discovered anti-avian influenza agents from plant origins up to December of 2015 is provided. After introducing the epidemics of avian influenza and the current preventive measures and treatments, a brief summary of the influenza A virus replication cycle is illustrated, in which the major processes of viral infection are discussed. The ethnopharmacology of anti-avian influenza plant-based natural products is reported. These botanical anti-avian influenza agents are further presented according to their modes of action and molecular targets. The actions of plant-based natural products typically range from interfering with the viral entry, replication, transcription and translation, nuclear export of viral materials, viral assembly, packing, budding to enhancing the host response against the viral infections. Moreover, the chemical structures and challenges in the discovery of some typical anti-viral compounds are explained in detail. According to this review, hundreds of botanical anti-avian influenza agents have been discovered. Conclusion: Collectively, the discovery of anti-avian influenza agents derived from plants largely involves multidisciplinary approaches of botanical, phytochemical and biological techniques, which are also heavily applied to the development of synthetic compounds for other therapeutic uses.

Background: The human body has natural defenses against viruses. During the virus infection, as a self-protective mechanism, immune cells and other cells will secrete amount of antiviral cytokines to promote the host to clear virus and microorganism, with multiple mechanisms such as alteration of major histocompatibility complex (MHC) molecules, activation of cellular antiviral responses involving natural killer cells (NK cells) and cytotoxic lymphocytes (CTLs), production of antiviral proteins and antibodies. Natural products as traditional pharmaceutical sources for the curability of various illnesses in the form of medicines possess immunostimulatory properties to enhance the immune system and eventually combat the disease or infection. In the past 20 years, numerous natural products have been subjected to investigation for their antiviral effects and many of them such as polyphenols, flavonoids, saponins and polysaccharides exhibit significant antiviral effects via regulation of these cytokines, specifically interferons (IFNs), tumor necrosis factor α (TNF-α) and interleukins (ILs). Objective: The purpose of this review is to provide an overview of antiviral cytokines and regulation functions of natural products on antiviral cytokines, demonstrating natural products as a promising source for discovery of antiviral agents for the prevention and treatment of virus infection via regulating endogenous antiviral cytokines.

Background: Despite the successes achieved recently in the treatment of various infectious diseases, the morbidity and mortality associated with malaria remain major burdens. Objective: The main limitations of conventional malaria therapy are the development of multi-drug resistance resulting in high dosage of different drugs and subsequent pill burden and toxicity. Thus, new effective antimalarial agents are urgently needed due to the increasing drug resistance of Plasmodium sp. Discussion: Nature is successful in providing mankind with compounds against infectious diseases. Many of small drugs on the market were originally developed from natural-based compounds. Scaffolds, such as monoor diazanaphthalenes, naphthoquinone, indole, pyrrole or endoperoxides can be considered as privileged structures for the discovery of new antimalarials. Nevertheless, some difficulties associated with natural lead compounds derived from these scaffolds, such as their synthesis, limited aqueous solubility, chemical or metabolic instability and wide spectrum of biological effects are needed to be solved. Conclusion: Thus, semisynthetic or synthetic analogues of natural antimalarial agents exhibiting optimized physicochemical properties, more selective biological activity and/or higher potency especially against resistant or multidrug resistant strains have been designed. The review is focused on selected recently reported potential antimalarial agents derived from isolated bioactive natural compounds based on the above-mentioned scaffolds. Their mechanism of action and structure-activity relationships are briefly mentioned.

Background: Phenolic compounds are a class of the most widely distributed secondary metabolites in plants. They may function as pollination, pigment constituents and protection against UV radiation and predation for plants. Plant phenols have been studied for hundreds of years, and have acted as the major class of compounds that show great activity against various viruses such as herpes simplex, Epstein-Barr virus, equid herpesvirus, hepatitis B virus, human immunodeficiency virus, respiratory syncytial and canine distemper viruses. Because of the extensive antiviral activities, phenolic compounds have been widely investigated both chemically and biologically. The distribution of hydroxyl groups and ester group accounts for different antiviral activities of phenolic compounds, and research of these compounds has revealed that phenols have great potential for the development as therapeutic agents against various viruses. As a result, dozens of phenols in functional foods have been discovered to display antiviral activity. Objective: This review emphasizes structure classification and antiviral activities of plant phenolic compounds, which are expected to provide guides for rational design of antiviral drugs.

Objective & Background: In this review, we summarize the principle and applicability of hyphenations of planar chromatography in natural product research. Direct bioautography, the combination of planar chromatography with antimicrobial assay, is suitable for rapid, high-throughput screening of plant extracts, and can be used as a bio-monitoring system in effect-directed processes. It permits testing of separated, individual matrix components against various bacterial or fungal species. Discussion: The bioautogram (developed adsorbent layer immersed into a cell suspension) can be visualized using vital dyes or by detecting the emitted light of luminescent cells. Further characterization of active compounds, selected according to the bioautogram, can be carried out in or ex situ by spectroscopic (e.g., FTIR, FT-Raman, SERS, NMR) and/or spectrometric (MS with various ionization techniques) techniques. In the last decade, intense innovation work on planar chromatography-mass spectrometry implemented a rapid characterization of separated components by the use of a manually operated, pneumatically driven TLC-MS interface comprising an elution head or by techniques with one-step desorption and ionization that can be carried out with spray, laser or excited gas beam. The advantages of overpressured layer chromatography (OPLC) in these approaches are also demonstrated.

Objective & Background: Emergence and spreading of antimicrobial resistance is one of the serious challenges of modern medicine. Many microorganisms acquired various resistance mechanisms, including mutations of the antimicrobial targets, adoption of resistance genes coding for enzymes degrading or modifying the antimicrobial molecules, protecting or modifying the antimicrobial targets, or coding for efflux systems that pumps the antimicrobials out of the cells. The spectrum and quantity of medically important microbial strains resistant to antimicrobials are steadily increasing. Nowadays, the antimicrobial resistance poses a real threat of the postantibiotic era, and increases mortality and morbidity of infected patients, as well as the cost of health care expenses. Conclusion: The effort of current pharmaceutical research is to search for new classes of active compounds with better antimicrobial activity and different target sites than antimicrobial drugs in current use. Alkaloids, essential oils and phenolic compounds such as tannins, phenolic acids and flavonoids are important groups of plants secondary metabolites that are not essential for plant survival but are significant for their defense, especially against microbial pathogens. Several studies investigated and approved their antimicrobial effects also in human medicine. These compounds are promising alternative natural antibacterial, antiviral and antifungal agents.

Background & Objective: Fungi are responsible for producing infections in humans. While all humans are susceptible to these disorders, immunocompromised people are the most at risk. Although it appears that we have many antifungal drugs in clinical use, unfortunately, most antifungal drugs currently in use have serious limitations or some drawbacks in pharmacokinetic aspects such as they do not possess an adequate solubility. As complement, fungi have developed a significant resistance against them because of their indiscriminate and even irrational use in some cases. Considering such situation, there is an urgent need to develop new and more effective antifungal drugs. Discussion: For such reason, in recent years there has been an incredible increase in the number of studies looking for new compounds with antifungal effects; in particular new structures obtained from natural products. While a large number of compounds with antifungal activities (some of them with novel structures) have been reported, very few have managed to be used therapeutically. In this review article, we have identified and discussed the main reasons for the poor results that have been obtained so far in order to find new antifungal drugs. Also, new strategies which could be under way to improve the search for new antifungal agents for therapeutic use are discussed here, remarking their scope and limitations.

Background: The quinoline moiety has been reported to be a privileged structure due to its presence in many drugs. It appears in alkaloids and natural products such as quinine, camptothecin or cinchonidine. The spectrum of the activity of quinoline-related compounds includes not only antimicrobial but also anticancer effects. Objective: Those active quinoline alkaloids have become the basis for a large number of synthetic drugs.Nowadays, more than a third of quinoline-derived drugs have a natural provenance. There are also a number of quinoline alkaloids that have been used extensively for treating neglected diseases in traditional medicine. Interestingly, most of the active plants predominantly populate countries that suffer most from such diseases. In this work, quinoline alkaloids that have an antimicrobial activity that might be relevant to neglected diseases are reviewed.

Background: Athletes' food disease is a general name for the tinea pedis. This kind of disease bothers foot of billions of people with intense itching, burning and stinging. Athletes' foot disease is mainly caused by the ringworm fungi known as dermatophytes. Those dermatophytes commonly show resistance to antibiotics. Therefore dermatophytes infection recurs easily. Objective: Natural compounds from plants and microorganisms are always the most important sources of antifungal agents. In this review, the antifungal natural agents against four common tinea pedis dermatophytes (Epidermophyton floccosum, Trichophyton mentagrophytes, T. tonsurans and T. rubrum) will be introduced in details. Method: These natural products are divided into 2 parts: 61 active compounds and plant extracts (including essential oils). The compounds were classified into 9 categories according to their chemical structures, which are coumarin, lignan, terpenoid, saponin, quinone, alkaloid, flavonoid, phenyl derivatives and others. Related pharmaceutical approach and extraction method of antifungal natural agents for tinea pedis will be discussed for future application.

Background & Objective: The emergence of multidrug-resistant virus, bacteria and fungi has created an urgent need for the development of novel antibiotic drugs from natural products with different mechanism of action. Therefore, in this review, seventeen types of isoquinoline alkaloids, including benzyltetrahydroisoquinoline, benzylisoquinoline, bisbenzylisoquinoline, aporphine, tetrahydroprotoberberine, N-methyltetrahydroprotoberberine, protoberberine, protopine, benzophenanthridine, dihydrobenzophenanthridine, pavine, cularine, phthalideiso-quinoline, spirobenzylisoquinoline, promorphine, morphine and ipecac, were screened and regarded as an attractive target for the discovery of new antiviral, antibacterial and antifungal lead compounds or agents. Method: Notably, sixteen types of alkaloids were biosynthesized from the central precursor benzyltetrahydroisoquinoline in herbal medicine. Finally, the antiviral and antimicrobial activities of 210 isoquinoline alkaloids were uncovered and the structure-activity relationships were also summarized. Conclusion: The quaternary nitrogen and the methylenedioxy at C-2 and C-3 played an important role in increasing the antiviral, antibacterial and antifungal activity of N-methyltetrahydroprotoberberine, protoberberine and benzophenanthridine alkaloids.