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Natural productsThere is a strong social interest in natural remedies more Essay

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1.1. Natural productsThere is a strong social interest in natural remedies more than 80% of the world populations depending on natural products for primary health care and medicine (Figueroa et al., 2012). Natural products (algae, bacteria, fungi, plants etc) have been used as an important source of healing agents for over millions of years and still several currently available today’s drugs are derived from natural products or their derivatives (Kinghorn et al., 2011; Newman and Cragg, 2012). These products have vast structural and chemical diversity that cannot be matched by any synthetic libraries of small molecules and continue to inspire new discoveries in biology, chemistry and medicine.

These small molecules (secondary metabolites) optimized as drug-like molecules and continue the best sources of drugs and drug leads (Newman and Cragg, 2012). Natural products and their derivatives have played a most important role in cancer treatment for more than 50 years, both in terms of giving established drugs and new lead compounds for synthetic optimization and in providing material for studying cellular and molecular mechanisms of action relevant to cancer inhibition (Cragg et al.

, 2012; Butler et al., 2014; Newman and Cragg 2016). Natural products also persist to be the basic source for antibacterial drug invention as 66% of the all the drugs presently accepted as antibacterial agents are comes from natural products (Brown et al., 2014). The modern decades are characterized by the new discoveries of microorganisms gifted of producing compounds as a potential resource of novel antibiotics (Ullah et al., 2017). Over the last numerous decades, natural products have continued to play an important responsibility in the development of novel drugs (Harvey, 2008).1.2. Current global problems to human healthAntimicrobial resistance (AMR) is a universal public health threat to human health (Carlet et al., 2011). The yearly death rate for infections caused by antibiotic resistant bacteria amounts to as a minimum 50000 in Europe and the USA alone and many more in other parts of the world. Generally recognized as an important health threat by organizations and institutions such as the WHO and the European Union and the World Economic Forum, AMR has the possible to return us to the dark age of medicine’ (Neill, 2014). Despite emergence of highly resistant microorganisms and the vast medical need for new drugs, the improvement of antibacterial has slowed to an unacceptable level worldwide (Bragginton and Piddock 2014). Cancer is now regarded as the second foremost cause of death, and remains a main cause of morbidity throughout the world (Arnold et al., 2015)1.2.1. Antimicrobial resistance To battle against microbes or infections, definitely antibiotics are a blessing to human civilization that has saved millions of people from deaths. Numerous varieties of the antibiotics have been used for remedial purposes overtime. Antibiotics were seen as the wonder drug’ in the mid-20th century. At the time, there was a hopeful belief that transmissible disease was nearly coming to a complete halt (Sojib et al., 2017). The starting of modern antibiotic era was synonymously connected with two names Alexander Fleming and Paul Ehrlich. Antibiotics were considered a wonderful bullet that selectively targeted microorganisms that were responsible for sickness causation, but at the same time would not affect the host. Fleming was the first used penicillin as a potential resistance against bacterial infections treatment (Aminov, 2010). Antibiotics either are cytostatic or cytotoxic to the microorganisms, allowing the body’s natural defenses, such as the immune system, to eliminate the microorganism from host. These antibiotic drugs often act by inhibiting the synthesis of a bacterial cell, synthesis of proteins, ribonucleic acid (RNA), deoxyribonucleic acid (DNA), by a membrane disorganizing representative, or other specific actions. Antibiotics may also go into the cell wall of the pathogens by binding to them, using the energy-dependent transport mechanisms in ribosomal sites, which consequently lead to the inhibition of the protein (Levy and Marshall 2004). However, due to the huge and irresponsible use of the antibiotics, has contributed an appreciably to the initiation of the resistant strains (Chopra et al., 2002). Antimicrobial resistance (AMR) occurs when bacteria, fungi and viruses, they become resistant to antimicrobial drugs that are used for treating the infections they cause. Every time an antimicrobial medicine is used for cure disease, it decreases the effectiveness for all users, because over usage increases the possibility for the bacteria to become resistant. Resistance against antibiotics drugs is an urgent trouble because antibiotics are a foundation of modern medicine and the majority medicinal procedures in human and animal health rely on functioning antibiotics (Poonsuk et al., 2014). AMR will increase communicable disease, slowing down livestock productivity and troublemaking international trade (Goutard et al., 2017). Drug resistant bacteria have become a world concern, and the search for new antibacterial agents from natural sources is therefore urgent and ongoing (Fancher, et al., 2016).1.2.2. CancerCancer is the one of major cause of mortalities all over the world. Cancer is characterized by uncontrolled multiplication of cells within the human body (Ochwang et al., 2014). In between the year 2005 to 2015 cancer causing approximately 84 millions of deaths by the report of world health organization (WHO) (Behzad et al., 2014). Genetic predisposition, incorrect diet and environment are main reasons for the majority of the cancers. Among these 95% of all cancers are caused by life style and may take as long as 20″30 years to develop. Current estimate from the American Cancer Society and from the International Union Against Cancer indicate that 12 million patient of cancer were diagnosed last year, with 7 million deaths worldwide; these numbers are expected to double by 2030 (27 million patient with 17 million deaths) (Aggarwal et al., 2009). Despite modern improvements in survival rates due to advances in early detection and the excellence of treatment available, cancer remains a major public health hazard in countries all over the world (Miller et al., 2016; Siegel et al., 2016). The available anticancer drugs can destroy the cancer cells, at the same time it causes significant side effects to healthy cells and tissue (Liu et al., 2015). Thus, the development of new anticancer drugs with more effective and safe to the healthy cells is an urgent need. Natural products and their derivatives played important role in the development of new anticancer drugs (Greenwell and Rahman, 2015).1.2.3. BiofilmsPathogenic microbial biofilm is measured a universal challenge due to the intrinsic antibiotic resistance conferred by its lifestyle. By living in a community in a clinical condition, microbial organisms are responsible for severe and hazardous cases of infection. Combating this organization of cells usually requires high antibiotic doses for a prolonged time, and these approaches often fail, contributing to infection persistence (Wesgate et al., 2016). Antimicrobial resistant cells usually require high antibiotic doses for an extended time, and these approaches often fail, contributing to infection persistence (Wesgate et al., 2016). Besides therapeutic limitations, biofilms can be a source of infections when they grow in medical equipment. The challenge compulsory by biofilms has mobilized researchers in the entire world to propose or develop alternatives drugs to control biofilms from natural products.1.3. Need for new drugsThere is a common call for novel antibiotics and chemotherapeutic agents that are very effective, low toxicity, and have a slight environmental impact. In the face of rising health consequences or side effects of these of synthetic drugs in the fight of diseases, new and safer alternative could be in the use of natural products (Gupta et al., 2014; Elansary and Mahmoud, 2015). Natural products have complex structures with unique mode of action. But in synthetic chemistry all natural products and their derivaties (taxol, vincristine and morphine) cannot be synthesized because these molecules possess complicate structures that are too hard and expensive to synthesize on an industrial scale and hence such compounds can only be obtained from natural sources (Mouhssen, 2013). Berdy (2012) reported that about 10 millions of chemical compounds are synthesized by pharmaceutical industries, from these little amount only 2000 to 2500 compounds have been used as drugs for cure diseases that accounted for 0.005% of the total synthetic compounds, whereas only 500,000 compounds have been obtained from nature, but most of compounds 1200 to 1300 are widely used as drugs that account as 0.6% of the total number. Additional benefit to the natural products is that they are safe and do not have any side effects for host. So, natural products and their derivatives can be considered as an important component in the search and development for new and safe drugs.1.4. Sources of natural productsNature is an attractive source of new healing candidate compounds as a wonderful chemical diversity. These chemical compounds are found in millions of species of animals, marine organisms, microorganisms and plants as potential anti-cancer agent (Newman et al., 2003; Butler, 2004). However, their present implementation in drug discovery and development efforts have somewhat demonstrated a turn down in interest (Mishra and Tiwari 2011). Nevertheless, natural products and their derivates continue to grant unique structural diversity in comparison to currently available standard combinatorial chemistry, which presents opportunities for discovering mainly new low molecular weight lead compounds. Since less than 10% of the world’s biodiversity has been assessed for potential biological activity, still many more useful natural lead compounds wait for discovery with the challenge being how to access this natural chemical diversity (Cragg and Newman 2005).1.4.1. Natural products from plantsMedicinal plants have been used since time immemorial for the therapeutic of different infections and maintain to supply front-line pharmacotherapy for millions of people globally (Naidoo et al., 2016). Medicinal plants are an important part of alternative and complementary drugs (Masafu et al., 2016). Plants have well-established history, exclusive chemical diversity and interesting biological properties (Corson and Crews, 2007). Drugs derived from medicinal plants maintain a significant advantage as they present a stable market throughout the world (Bhagat et al., 2016). Plants have a wonderful capability to produce a wide diversity of secondary metabolites, like alkaloids, glycosides, terpenoids, saponins, steroids, flavonoids, tannins, quinines and coumarins (Das et al., 2010). Plant-derived biomolecules could be important antimicrobial substances (Srivastava et al., 2013). A few natural products are greatly efficient in the treatment of bacterial diseases (Fernebro, 2011). 1.4.2. Natural products from microorganisms Compared to other natural product sources such as plants, microorganisms have a huge diversity but little bit only evaluated for their biological activity. The ecosystem of microorganisms enables them to produce a variety of substrates, these metabolites help to adapt their biological environment (Fernandes et al., 2009). Microorganisms are significant source in the production of bioactive natural compounds with massive application potential in the discovery of novel molecules for drug discovery, in industrial and agricultural applications (Kellernp, 2005; Strobel, 2006; Porras and Bayman 2011). An examination of agrochemical and pharmaceutical agents from cyanobacteria showed a discovery rate for bioactive compounds of approximately 7%, which is typical for microorganisms (Carmichael, 1992). Fungi have led to the improvement of various drugs, including cholesterol-lowering agents, beta-lactam antibiotics, and immunosuppressant (Butler et al., 2014; Newman and Cragg, 2014). Since the ancient time people consume diverse natural sources for the treatment of diseases. Among such natural sources microbial products and their derivatives have been considered one of the potent resources for drug discovery due to their diverse biological activities.1.4.2.1. Natural products from Soil fungiFungi is a eukaryotic microorganisms, can occur as unicellular (yeasts), filamentous (molds) form. Yeasts are minute fungi consisting of single cells that reproduce by budding while molds, in contrast, occur as long filaments known as hyphae, which grow by apical extension (Aggarwal, 2010; Baron, 1996). Soils are extremely complex, having various constituents performing different functions mainly due to the activity of soil organisms (Ullah et al., 2017; Raja et al., 2017; Kostadinova et al., 2009). The microorganisms plays important role in soil ecosystem. The soil worth is determining by microbial composition and functioning changes during decomposition of organic matter, recycling of nutrients and biological control (Stefanis et al., 2013). Commonly, soil is an oligotrophic habitat for fungi because the fungal growths are partial and readily present for little periods in a restricted zone. Fungi are playing an important role in the daily life of human beings in addition to their participation in agriculture, bioremediation, food industry, medicine, natural cycling, bio-fertilizers and other ways leading to human welfare (Kirk, 2004; Karthikeyan et al., 2014). Fungi produce many antibiotics, having antibacterial and antifungal activity, which are generally used as drugs over the world particularly the penicillin, cephalosporin and fusidic acid (Dobashi et al., 1998). The modern decades are characterized by the new discoveries of microorganisms capable of producing compounds as a potential source of new antibiotics (Ullah et al., 2017).1.5. Molecular docking studies Sequencing of the human genome has led to improve in the number of new remedial targets for pharmaceutical research. In addition, high-throughput crystal-lography and nuclear magnetic resonance methods have been further developed and contributed to the gaining of the atomic structures of proteins and protein”ligand complexes of a rising level of detail (Gore and Desai, 2014). Molecular docking is a computational technique used to guess the communication of two molecules generating a binding model. In numerous drug discovery applications, docking is done between a small molecule and a macromolecule for example, protein-ligand docking. Nowadays docking is also applied to guess the binding mode between two macromolecules, for example protein-protein docking. At present, molecular mechanics is the foundation for most docking programs. Various in vitro, in vivo, and computational methods were employed to evaluate the antimicrobial and anticancer potential of drugs or chemicals. Among these methods, docking is the most important method in drug designing for cancer (Zahra et al., 2013; Tabassum et al., 2014).1.6. Objectives Isolation and identification of fungal species from forest soil for their antibacterial potential. Optimization of fungal growth conditions to enhance antibacterial activity. Determine the MIC and MBC value of the fungal extract against bacterial pathogens. To evaluate the Biofilm and Antibiofilm assay of was carried out against pathogenic bacteria. To identify the bioactive compounds of fungal extract using GC-MS analysis. To assess the bioactive potential of fungal metabolites, through in vitro anticancer assay was carried out against human breast, larynx, liver and skin cancer cell lines. To support the anticancer properties of fungal metabolites by molecular docking.

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