Showing papers in "Current Bioactive Compounds in 2008"
TL;DR: Drug discovery based on Ayurveda follows a ‘Reverse Pharmacology’ path from Clinics to Laboratories using principles of systems biology where holistic yet rational analysis is done to address multiple therapeutic requirements.
Abstract: While biotechnological advances, genomics and high throughput screenings or combinatorial and asymmetric syntheses have opened new vistas in drug discovery, the industry is facing a serious innovation deficit. Critics suggest that “we have become high throughput in technology, yet have remained low throughput in thinking”. Post marketing failures of blockbuster drugs have become major concerns of industries, leading to a significant shift in favor of single to multi targeted drugs and affording greater respect to traditional knowledge. Typical reductionist approach of modern science is being revisited over the background of systems biology and holistic approaches of traditional practices. Scientifically validated and technologically standardized botanical products may be explored on a fast track using innovative approaches like reverse pharmacology and systems biology, which are based on traditional medicine knowledge. Traditional medicine constitutes an evolutionary process as communities and individuals continue to discover practices transforming techniques. Many modern drugs have origin in ethnopharmacology and traditional medicine. Traditions are dynamic and not static entities of unchanging knowledge. Discovering reliable ‘living tradition’ remains a major challenge in traditional medicine. In many parts ‘little traditions’ of indigenous systems of medicine are disappearing, yet their role in bioprospecting medicines or poisons remains of pivotal importance. Indian Ayurvedic and traditional Chinese systems are living ‘great traditions’. Ayurvedic knowledge and experiential database can provide new functional leads to reduce time, money and toxicity the three main hurdles in the drug development. We begin the search based on Ayurvedic medicine research, clinical experiences, observations or available data on actual use in patients as a starting point. We use principles of systems biology where holistic yet rational analysis is done to address multiple therapeutic requirements. Since safety of the materials is already established from traditional use track record, we undertake pharmaceutical development, safety validation and pharmacodynamic studies in parallel to controlled clinical studies. Thus, drug discovery based on Ayurveda follows a ‘Reverse Pharmacology’ path from Clinics to Laboratories. Herein we describe such approaches with selected examples based on previous studies.
107 citations
TL;DR: This mini-review summarizes major recent developments on natural, synthetic iron chelating compounds and hydrogen peroxide-triggered prochelators as potential candidates for PD treatment.
Abstract: Parkinson's disease (PD) is a neurological disorder characterized by the progressive impairment of motor skills in patients. Growing evidence suggests that abnormal redox-active metal accumulation, caused by dysregulation, plays a central role in the neuropathology of PD. Redox-active metals (e.g. Fe and Cu) catalyze essential reactions for brain function. However, these metals can also participate in the generation of highly toxic free radicals that can cause oxidative damage to cells and ultimately lead to the death of dopamine-containing neurons. The emergence of redox-active metals as key players in the pathogenesis of PD strongly suggests that metal-chelators could be beneficial in the treatment of this condition. This mini-review summarizes major recent developments on natural, synthetic iron chelating compounds and hydrogen peroxide-triggered prochelators as potential candidates for PD treatment.
63 citations
TL;DR: In this article, a review of methods to generate the amorphous phase, estimate the degree of crystallinity of the polymeric phase, predict the stability of the ammorphous phase against crystallization, and choose the polymers carrier and formulation of the preclinical phase for preclinical studies is presented.
Abstract: A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have a significant impact on the development of the compound. Compounds with low bioavailability pose a greater challenge in early preclinical work involving animal studies, where obtaining maximum exposure is the primary goal especially in toxicology studies designed to establish the safe dose. From the standpoint of maximizing exposure, the amorphous phase is of great interest as pharmaceutical materials since it is the most metastable state and as such offers the potential of higher solubility and better bioavailability. However, the amorphous approach is not actively pursued in preclinical work owing to the tendency of the amorphous phase to crystallize thereby neutralizing the solubility advantage. This review focuses on (i) methods to generate the amorphous phase, (ii) methods to estimate the degree of crystallinity of the amorphous phase, (iii) methods to predict the stability of the amorphous phase against crystallization, and (iv) choice of polymers carrier and formulation of the amorphous phase for preclinical studies.
62 citations
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TL;DR: Previous reports are compromised because IACs have not been employed in PCR and mutagens and inhibitors may affect the very stability essential for NA analyses used in diagnostics and phylogenetics.
Abstract: Microorganisms manufacture prolifically bioactive compounds. For example, fungi produce antibiotics and mycotoxins. However, many are difficult to identify and classify. Methods which rely on nucleic acid (DNA/RNA) are increasingly being used for this purpose where strains are grown in liquid or agar culture and often subjected to polymerase chain reaction (PCR) analyses. It has not been considered that self-produced mutagenic and inhibitory secondary metabolites (SM) affect DNA analysis of the target fungi. The most obvious mycotoxins and fungi to consider in this regard are aflatoxins (AFB) and Aspergillus, as AFB are the most mutagenic natural compounds. Many other fungi and SM are relevant and fungi act as a model for bacteria and plants. In fact, fungi repair damaged nucleic acid (NA) and are capable of removing toxins by employing transporter proteins. Nevertheless, these could be inhibited by bioactive metabolites. Mutagenic effects may involve inhibition of DNA stabilising enzymes. In addition, PCR is subject to false negative results. Samples of fungi with the genes of interest (e.g. a mycotoxin) may be categorized as negative and safe as a consequence. Internal amplification controls (IACs) will ameliorate the situation and need to become mandatory. These are conventionally NA that posses a sequence which will provide a PCR product (a) using the same primers employed for the target gene and (b) that will not coincide on the gel with the product of the target gene. Inhibitors and mutagens in cultures need to be minimized, and SM are an obvious source. This is a crucial issue in developing diagnostic and phylogenetic methods. The conclusions are (a) previous reports are compromised because IACs have not been employed in PCR and (b) mutagens and inhibitors may affect the very stability essential for NA analyses used in diagnostics and phylogenetics.
19 citations
16 citations
TL;DR: Preliminary screening showed anise seed extracts to be more active than celery seed extracts and hexane produced the best extract of anise seeds giving a mildly potent lethal concentration of 403.84 mg/L.
Abstract: The larvicidal activity of Pimpinella anisum (anise) and Apium graveolens (celery) seed extracts was evaluated against 4th instar Aedes aegypti larvae under laboratory conditions as per WHO methodology. Preliminary screening showed anise seed extracts to be more active than celery seed extracts and hexane produced the best extract of anise seeds giving a mildly potent lethal concentration of 403.84 mg/L. Other researchers have reported higher efficacies which cannot be explained by differences in extraction method or choice of solvent. Other probable causes of efficacy variability in phytochemical potency studies are discussed and bioinsecticide screening standards are recommended.
TL;DR: Different classes of potent natural compounds that have impressive gastro-protective property against various ulcerogens (except Helicobacter pylori infection), and are available in large quantities from the natural sorces are covered.
Abstract: Extensive use of certain drugs, changes in lifestyles and food habits, as well as stress factors in modern human lives have led to an exponential increase in the incidence of gastric ulceration. The ideal anti-ulcer drug with less side effects and recurrence, and affordability has so far remains elusive, providing avenues for innovation, especially with phytochemicals. This review furnishes extensive information on the earlier works carried out in this area and rationalizes the mode of action of them, citing limitations of the previous studies. The primary aim was to cover different classes of potent natural compounds that have impressive gastro-protective property against various ulcerogens (except Helicobacter pylori infection), and are available in large quantities from the natural sorces. A few examples of synthetic congeners have also been included to highlight the type of innovation that may be required for developing new drugs.
TL;DR: The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species were identified as contributing to the mosquito bite-deterrent activity that was first indicated by folkloric usage.
Abstract: About 20 species from Callicarpa have reported ethnobotanical and ethnomedical uses, and several members of this genus are well known in the traditional medical systems of China and South Asia. Ethnomedical reports indicate their use in the treatment of hepatitis, rheumatism, fever, headache, indigestion, and other ailments. Several species of Callicarpa have been reported to be used against cancer (e.g., Callicarpa americana root to treat skin cancer and Callicarpa rubella bark to treat tumors of the large intestine). Extracts from about 14 species in this genus have been evaluated for biological activity, including antibacterial, antifungal, anti-insect growth, cytotoxic, and phytotoxic activities. In addition to amino acids, benzenoids, simple carbohydrates, and lipids, numerous diterpenes, flavonoids, phenylpropanoids, phytosterols, sesquiterpenes, and triterpenes have been detected in or isolated from the genus Callicarpa. The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species (and C. japonica) were identified as contributing to the mosquito bite-deterrent activity that was first indicated by folkloric usage. Recent bioassay-guided investigations of C. americana extracts have resulted in the isolation of several active compounds, mainly of the clerodane diterpene structural type.