4^th International Conference and Exhibition on Natural Products, Medicinal Plants & Marine Drugs June 11-12, 2018 Rome, Italy

Natural products (secondary metabolites) have been the most successful source of leads for potential drug discovery. Natural products have been well documented for their medicinal uses for thousands of years. Plants have evolved and adapted over millions of years to withstand bacteria, insects, fungi and weather to produce unique, structurally diverse secondary metabolites. Their ethno pharmacological properties have been used as a primary source of medicines for early drug discovery. Macro and micro fungi have been part of human life for thousands of years. They were used as food (mushrooms), in preparation of alcoholic beverages (yeasts), medication in traditional medicine and for cultural purposes

Natural products have served as the source and inspiration for a large fraction of the current pharmacopoeia. Although estimates vary depending on the definition of what is considered a natural product-derived drug, it is safe to say that between 25 and 50% of currently marketed drugs owe their origins to natural products. Thus, a review by Newman and Cragg analysing the sources of new drugs from 1981 – 2006, and using a fairly broad definition of what constitutes a “natural product derived drug”, indicates that almost 50% of new drugs introduced during this period had a natural product origin. In the case of anticancer and anti-infective agents the proportion is even higher, and one estimate is that almost two-thirds of such agents are derived from natural products.

Marine (or blue) biotechnology encompasses the applications of biotechnology tools on marine resources. Marine biotechnology encompasses those efforts that involve the marine resources of the world, either as the source or target of biotechnology applications. Marine biotechnology may include techniques such as bioprocessing, bioharvesting, bioprospecting, bioremediation, using bioreactors etc (so called process biotechnology techniques); aquaculture/fisheries; gene, protein, or other molecule based techniques; while applications may include: health, food, cosmetology, aquaculture, agriculture, fisheries, manufacturing, environmental remediation, biofilms and corrosion, biomaterials, research tools etc. Therefore, marine biotechnology has a horizontal scope encompassing very different applications, for all of which the marine environment is providing the resources.

The global market for marine biotechnology products and processes is currently estimated at € 2.8 billion (2010) with a cumulative annual growth rate of 4-5 %. Less conservative estimates predict an annual growth in the sector of even up to 10-12 % in the coming years, considering the huge potential and high expectations for further development of this sector at a global scale.

The Global Marine biotechnology market is expected to reach $5.9 billion by 2022 growing at a CAGR of 6.2% from 2014 to 2022. The growth factor for marine biotechnology market is increase in the demand for natural products. The key drivers for the market are new applications of marine derived enzymes in cosmetics industry and use of marine algae and micro algae in bio-field production. The increase in demand for commodities has resulted in supply shortages and high prices in crude oil, steel and other metals. Developing countries face a challenge as they do not often have the established industrial infrastructure to act as sub-contractors. The market has also been witnessing increasing investments from venture capitalists. However, high R&D costs could pose a challenge to the market growth.

Natural products are believed to have the advantage of having enormous structural and chemical diversity, increased protein binding characteristics (due to complex structure) and specific biological activity. Also these serve as good lead compounds suitable for further modification. Bioactive compounds from marine flora and fauna have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Several molecules isolated from various marine organisms (microorganisms, algae, fungi, invertebrates, and vertebrates) are currently under study at an advanced stage of clinical trials, some of them have already been marketed as drugs.

Increasing marine biodiversity preservation and research programs throughout the world are a definite sign that the world is getting ready for a new variety of pharmaceutical compounds that would be fighting a broad spectrum of diseases. With an estimated 70% organisms to be investigated, pharmaceutical companies hope to find a cure for high-risk and fatal diseases in the coming years. Marine organisms are expected to be viable for production of drug compounds, biomaterials, nutritional supplements, and several types of algae are being used for the production of alcohol as an energy source.

The investigation of biological and chemical properties of natural products for the past two centuries has not only produced drugs for the treatment of several diseases, but has instigated the development of synthetic organic chemistry and the arrival of medicinal chemistry as a major route to discover efficacious and novel therapeutic agents. Structural alteration of natural compounds or synthesis of novel compounds, based on designs following a natural compound scaffolding, have offered us a lot of vital new drugs in the fields of medicine, agriculture, and food spheres. Nature has provided a fascinating array of chemical structures in the form of bioactive secondary metabolites

The natural and organic personal care market in Europe to grow at a CAGR of 9.58% during 2014-2019.The report covers the present scenario and the growth prospects of the natural and organic personal care market in Europe for the period 2015-2019. According to the report, the economy of Europe is on the path of recovery from the Eurozone crisis and the recession of 2008-2009. The resultant rise in GDP and PPP has led to increased disposable incomes and higher willingness among consumers to pay premium prices for natural and organic personal care products. Changing consumer lifestyles, improving standards of living, and growing consciousness about health and environmental issues are likely to lead to increased demand for natural and organic personal care products during the forecast period.

Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. An advance in technology and sensitive instrumentation for the rapid identification of novel bioactive natural products and structure elucidation continues to improve the natural product discovery process. Chemistry has indeed revolutionized the development of novel active chemical leads resulting in the synthesis of structural analogues. Natural products constitute a key source of pharmacologically active ingredients in a variety of novel agents with therapeutic potential in a wide range of diseases. Pharmaceuticals containing natural products or compounds derived from natural product scaffolds or templates have to undergo the same stringent approval process as drugs obtained from purely synthetic origin.

Natural products remain the best sources of drugs and drug leads, and this remains true today despite the fact that many pharmaceutical companies have deemphasized natural products research in favor of HTP screening of combinatorial libraries during the past 2 decades.  From 1940s to date, 131 (74.8%) out of 175 small molecule anticancer drugs are natural product-based/inspired, with 85 (48.6%) being either natural products or derived therefrom.  From 1981 to date, 79 (80%) out of 99 small molecule anticancer drugs are natural product-based/inspired, with 53 (53%) being either natural products or derived therefrom.  Among the 20 approved small molecule New Chemical Entities (NCEs) in 2010, a half of them are natural products. Natural products possess enormous structural and chemical diversity that is unsurpassed by any synthetic libraries.  About 40% of the chemical scaffolds found in natural products are absent in today’s medicinal chemistry repertoire.  Based on various chemical properties, combinatorial compounds occupy a much smaller area in molecular space than natural products.  Although combinatorial compounds occupy a well-defined area, natural products and drugs occupy all of this space as well as additional volumes.  Most importantly, natural products are evolutionarily optimized as drug-like molecules. This is evident upon realization that natural products and drugs occupy approximately the same molecular space.

The pharmaceutical industry’s interest in natural products diminished with the advent of such promising new technologies like combinatorial chemistry (CC) and high throughput screening (HTS). The prospect of such disciplines, aimed at accelerating drug discovery efforts, led some companies to dismiss their natural product programs. Combinatorial chemistry employs parallel synthesis techniques allowing the creation of libraries containing hundreds of thousands of compounds, whereas HTS allows rapid testing of large numbers of compounds. A significant number of drugs have been derived from plants that were traditionally employed in ethnomedicine or ethnobotany (the use of plants by humans as medicine as in Ayurvedic or Traditional Chinese Medicine), while others were discovered initially (through random screening of plant extracts in animals) or later, by determining their in vitro activity against HIV or cancer cell lines.

The past decade has witnessed a tremendous resurgence in the interest and use of medicinal plant products, especially in North America. Surveys of plant medicinal usage by the American public have shown an increase from just about 3% of the population in 1991 to over 37% in 1998. The North American market for sales of plant medicinal has climbed to about $3 billion/year. Once the domain of health-food and specialty stores, Phytomedicine have clearly re-emerged into the mainstream as evidenced by their availability for sale at a wide range of retail outlets, the extent of their advertisement in the popular media, and the recent entrance of several major pharmaceutical companies into the business of producing Phytomedicine products. No doubt a major contributing factor to this great increase in Phytomedicine use in the United States has been the passing of federal legislation in 1994 (Dietary Supplement Health and Education Act or “DSHEA”) that facilitated the production and marketing of Phytomedicine products.

The valuable medicinal properties of different plants are due to presence of several constituents i.e. saponines, tannins, alkaloids, alkenyl phenols, glycoalkaloids, flavonoids, sesquiterpenes lactones, terpenoids and phorbol esters. Among them some are act as synergistic and enhance the bioactivity of other compounds. Natural products (and conventional medicines) offer great anticipation in the identification of bioactive compounds and their development into drugs for the treatment of inflammatory diseases. Previously, the plant medicines were dispensed in the form of crude drugs like tinctures, teas, powders, poultices, and other herbal preparations. This eventually serves as the basis of the current modern drug discovery.

It has been estimated that about 80-85% of population both in developed and developing countries rely on traditional medicine for their primarily health care needs and it is assumed that a major part of traditional therapy involves the use of plant extracts or their active principles. In several countries, traditional medicine is still in vogue, and in fact, has been gaining more acceptability for treatment of chronic ailments. This is especially true for countries like India and China, which have a long tradition of fairly well-organized traditional therapy. In Africa, a great number rely on traditional medicine because of the availability and high cost of the synthetic drugs. About 20% of the population of the US takes herbal products, often in the absence of good evidence of their effectiveness. 

Dietary sources of natural products are assumed to have anti-cancer benefits include fruits, vegetables and spices yielding biologically active components such as curcumin, resveratrol, cucurbitacins, isoflavones, saponins, phytosterols, lycopene, and many others. A number of these are gaining importance as adjuvant anti-cancer agents with curcumin, resveratrol and cucurbitacins having activity reported against cancer stem cells.  39 natural compounds from marine species, mostly invertebrates, and 10 from microorganisms, mostly from bacteria of the Streptomyces genus, as potential new anti-cancer agents. It is assumed that many prokaryotic and eukaryotic natural product sources may still reveal a number of valuable anti-cancer compounds in the future and even ancient animal species have been suggested as a particularly valuable source.

Cancer is a well-recognized global health problem responsible for 7.6 million deaths (13% of all deaths) worldwide, which is expected to rise to 13.1 million by 2030 Despite the progress in the field of cancer research, both developing and developed countries are in the grip of this deadly disease, and still there is a need to discover and develop anti-cancer therapeutic agents. It has long been recognized that natural products represent the richest source of high chemical diversity, providing the basis for identification of novel scaffold structures that serves as starting points for rational drug design. This can be one of the reasons that efforts have been directed to discover promising cancer therapeutic agents from natural sources. Over the years, many natural product-based drugs have been introduced in the market. According to a recent review, 49% of drugs were either natural products or their derivatives that are used in cancer treatment. Moreover, between the year 2005 and 2010, 19 natural product-based drugs have been approved, among which 7, 10 and 2 have been classified as natural product (NP), semi-synthetic NPs and NP-derived drugs, respectively. Of these, five drugs, temsirolimus, trabectedin, ixabepilone, everolimus and romidepsin, have been developed in the area of oncology from 2007 to 2009. Indeed, it has been suggested that less than one-fifth of the ring systems found in natural products are represented in current trade drugs 

Many marine natural products appear to arise from multi-functional enzymes that are also present in terrestrial systems, exhibiting a cross phylum activity with terrestrial biota. However, a large number of marine derived compounds also possess a substantial amount of functional groups, which were not previously described from terrestrial metabolites. They range from derivatives of amino acids and nucleosides to macrolides, porphyrins, terpenoids, aliphatic cyclic peroxides, and sterols. Microorganisms (amongst them mostly bacteria and fungi) have played an important role in providing new structures, like antibiotics for drug discovery and development. The terrestrial microbial populations are immensely diverse which is also reflected in the number of compounds and metabolites isolated from these microorganisms. Besides bacteria, marine fungi and deep-sea hydrothermal vent microorganisms are reported to produce bioactive compounds and metabolites.

Marine organisms have been found to be capable of providing solutions for major human diseases such as cancer, Alzheimer’s, herpes and many others. With the rate of success and growth in this area, it is expected that the market for marine-derived pharmaceutical products will increase in the coming months rapidly and double by 2018.  Several of the marine organisms used for extracting drugs are deep sea bacteria, sponges, mollusks, fungi, and tunicates. Even with such strong R&D activities in marine organisms, it is believed that no more than 10% of organisms have been researched as potential candidates.

Drug discovery represents one of the most promising and highly visible outcomes of marine biotechnology research. Biochemicals produced by marine invertebrates, algae and bacteria, are very different than those from related terrestrial organisms and thus offer great potential as new classes of medicines. To date, examples of marine-derived drugs include antibiotics from fungi, two closely related compounds from a sponge that treat cancer and the herpes virus, and a neurotoxin from a snail that has painkiller properties making it 10,000 times more potent than morphine without the side effects. However, there are several more marine-derived compounds currently in clinical trials and it is likely that many more will advance to the clinic as more scientists look to the sea for these biotechnological uses. In addition to new medicines, other uses for marine-derived compounds include: cosmetics (algae, crustacean and sea fan compounds), nutritional supplements (algae and fish compounds), artificial bone (corals), and industrial applications (fluorescent compounds from jellyfish, novel glues from mussels, and heat resistant enzymes from deep-sea bacteria).

Primary research and market analysis shows sponges and marine animals to be the largest source of pharmaceutical products. In terms of geography, North America is expected to be the largest market for marine based pharmaceuticals. The history of marine-derived products began from cod-liver oil, shark oil, and calcium supplements. Marine biotechnology has developed over the years propelled by the unmet needs for new and innovative pharmaceutical products. Potential pipeline drugs being developed are anti-viral, anti-cancer drugs from byrozoans, anti-microbial, and anti-inflammatory. 

Natural Products are the source of    numerous pharmaceutical and agrochemicals agents, and it is reasonable to believe that there are additional agents in existence that remain undiscovered. These natural products are probably defence chemicals targeting and inhibiting the cell division processes of invading plant pathogens. The biofuels produced from the renewable resources could help to minimize the fossil fuel burning and CO2 production. Biofuel produced from biomass such as plants or organic waste could help to reduce both the world’s dependence on oil and CO2 production. These biofuels have the potential to cut CO2 emission because the plants they are made from use CO2 as they grow. Biofuels and bioproducts produced from plant biomass would mitigate global warming. This may due to the CO2 released in burning equals the CO2 tied up by the plant during photosynthesis and thus does not increase the net CO2 in the atmosphere.

Many drugs used today are from plants or are derived from plants. Approx. one-half of all licensed drugs that we were registered worldwide in the 25y period prior to 2007 were natural products or their synthetic derivatives. A review article on the sources of new drugs about 30 year period from 1981 to 2010 shows that a large percentage came from natural sources. It was also reported that among 19 natural product based drugs which were approved for marketing worldwide in between the year 2005 to April 2010, seven were classified as natural products, 10 semi-synthetic natural products and 2 natural product-derived drugs.

Marine bacteria have been proven to be a profound resource on the development of natural product chemistry and upon the medical sciences. The improvement of natural products-based screening, rather than relying on synthetic sources, has been the aim of current pharmaceutical research and development. Alternative strategies to consider include the identification of potential new antibiotics from commercial crude bacterial fermentations. Recent research progresses reported that many bioactive natural products from marine invertebrates have striking similarities to metabolites of their associated microorganisms including bacteria. Compared with terrestrial organisms, the secondary metabolites produced by marine organisms have more novel and unique structures owing to the complex living circumstance and diversity of species, and the bioactivities are much stronger. The study of marine bacteria and their potential role in the production of metabolites is becoming a new topic for research. Several investigations have supplied an increasing number of biologically active and structurally unique compounds. Bacteria and other micro-organisms are ubiquitous in the marine drugs. They are taxonomically diverse, biologically active, and colonize all marine habitats, from the deep oceans to the shallowest estuaries. It has been estimated that the majority of bacteria in natural aquatic ecosystems are organized in biofilms.

Approximately 30,000 structurally diverse natural products with a vast array of bioactivities have been discovered from marine organisms including microbes, algae and invertebrates. Invertebrates alone comprise approximately 60% of all marine animals and were described as the source of almost 10,000 new natural products since 1990 with a pronounced increase to about 1,000 compounds per year in more recent years By the turn of the 21st century larger percentages of bioactive NCEs were reported for marine organisms in comparison to terrestrial organisms, but nevertheless, marine chemical ecology is still several decades behind its terrestrial counterpart with respect to the total number of characterized and documented natural products  Kong et al. specifically compared natural products from terrestrial and marine sources.

About 50,000 compounds derived from microorganisms are produced commercially, according to Costa, but only a few hundred come from marine bacteria. As the marine microbiology industry is still young, new applications could be found among the millions of bacteria that have yet to be identified, according to Gram, who says that only a small percentage of marine bacteria have been grown in laboratory conditions.

Marine Probiotics are microorganisms that are believed to provide health benefits when consumed. The term probiotic is currently used to name ingested microorganism associated with beneficial effects to humans and animals. We usually think of bacteria as something that causes diseases. But your body is full of bacteria, both good and bad. Probiotics are often called "good" or "helpful" bacteria because they help keep your gut healthy. Probiotics are naturally found in your body. We can find them in some Natural Products and supplements. Lactobacillus and Bifidobacterium are the most common probiotic bacteria. The Lactobacillus genus has 18 different bacteria strains, while the Bifidobacterium genus consists of eight strains.

Natural products, although a valuable and precious resource, also come with their fair share of challenges in a variety of aspects. As mentioned before, one of the major issues concerning the use of natural products are the difficulties associated with obtaining sufficient amounts of material pure enough for discovery and development activities. If a compound is derived from a plant growing only in small quantities or remote locations or a marine organisms residing in great depth or difficult to access regions, Ayurveda medicine  re-supply becomes a problem. The threat of losing potentially valuable natural sources of pharmacologically active ingredients is constantly increasing due to the threat of extinction by deforestation of large landmasses and environmental pollution in remote areas as well as global warming. It is estimated that about 70% of the supply of herbal raw material other homeopathic medicine in India comes from the wild. To meet the increasing demand for raw material, to conserve wild resources, and to reduce the potential variability in the active ingredient content in medicinal plants from different collection areas, it is important to implement more controlled cultivation programs to ensure quality and to protect resources 

Natural product screening remains one of the most useful avenues for bioactive discovery. In the past decades, studies on MNP have been focused mainly on macroorganisms, i.e., sponges, corals and other marine invertebrates, although significant developments have been made in the microorganisms area. However, despite the large number of NCEs isolated from marine organisms, many of them with pronounced biological activity, the great majority does not surpass the pharmaceutical pre-clinical trials and only a very few have been marketed as pharmaceutical products. Besides the usual drawbacks in any drug discovery process, the industrial development of many promising MNP was hampered by additional difficulties such as sustainable source and issues related to structural complexity and scale up. Nevertheless, the global marine pharmaceutical pipeline remains very active and includes, at the moment, eight Food and Drug Administration (FDA) or European Medicines Agency (EMEA) approved drugs and several compounds in different phases of the clinical pipeline.

Cancer is one of the most serious fatal diseases in today’s world that kills millions of people every year. It is one of the major health concerns of the 21st century which does not have any boundary and can affect any organ of people from any place. Nanoparticles are rapidly being developed and trialed to overcome several limitations of traditional drug delivery systems and are coming up as a distinct therapeutics for cancer treatment. It is a challenge to eradicate tumor cells while sparing normal cells. We used magneto electric nanoparticles (mens) to control drug delivery and release.  Current treatment strategies for cancer also include combination of radiation, chemotherapy and surgery. Important issues in this research include physical-chemical assembly of the nanocarriers, their surface interactions with biological media, cellular interactions, and controlled content release from the carriers. Several strategies have been used to address mdr, especially p-glycoprotein-mediated drug resistance in tumors.

Medicinal chemistry is a discipline at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where they are involved with design, chemical synthesis and development for market of pharmaceutical agents. Earlier, medicinal chemists often optimized and developed compounds without much knowledge of the drug target or pathway in mind. New technologies have had a huge impact on drug discovery since the mid-20th century. Once hits are identified from high throughput screening (or other sources) the chemists may become involved in hit to lead (h2l) studies when hits from screens are effectively triaged and closely scrutinised for ability to serve as full blown lead compounds. Medicinal chemistry has, therefore, grown to encompass a greater range of scientific disciplines in the drug discovery process in order to minimize the cost, time and risk of development. The arrival of newer high powered computational capabilities was one catalyst for this approach. to succeed in the discovery process medicinal chemists have to perform these initial important tasks: identification of lead molecules which have the desired biological activity using new technologies such as hits and combinatorial chemistry, the lead modification or optimization which could be done by employing structure-activity analysis  and scale-up of the optimized lead for further drug development process and efficacy testing

Personalized medicine (pm) has the potential to tailor therapy with the best response and highest safety margin to ensure better patient care. Sequencing of the human genome at the turn of the 21st century set in motion the transformation of personalized medicine from an idea to a practice. Pharmacogenomics” (pgx) – the study of variations of DNA and RNA characteristics as related to drug response – is a critically important area of personalized medicine where significant progress has recently been made. Personalized medicinal drugs greatest strides have been in cancer.  a targeted treatment targets a cancer’s specific genes and proteins that allow the cancer cells to grow and survive FDA determines that products are safe and effective before marketing through a careful evaluation of benefits and risks that considers the available scientific data in the context of the underlying condition or disease.