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3
was merely based on the previous reports without any further investigation or information
on pharmacological activities or phytochemical composition (Thirumurugan et al., 2018).
TABLE 1.1 Plant-Based Secondary Metabolites as Antimicrobial Agents
Secondary Metabolites Source Activity References
Alkaloids
Affinin
Capsaicin
Lupanine
Anthraquinone
Hypericin
Glycosides
Glucoiberin
Glucoiberverine
Lignans
Dibenzocyclooctadiene
Styraxjaponoside C
Phenols
Catechol
Eugenol
Gallic acid
Pyrogallol
Resveratrol
Tannins
Ellagic acid
Terpenes
p-Cymene Thymus sp.
Limonene
Terpenoids
Carvacol
Thymol
Capsicum annuum
Capsicum annuum
Lupinus angustifolius
Hypericum perforatum
Lobularia libyca
Lobularia libyca
Schissandra chinensis
Styrax japonica
Phoenix dactylifera
Syzygium aromaticum
Terminalia chebula,
Leea indica
Emblica officinalis
Veratrum grandiflorum
Terminalia chebula
Citrus aurantium
Origanum vulgare
Thymus vulgaris
Antibacterial De and Goswami (2021)
Antibacterial, Antiparasitic
Antibacterial Romeo et al. (2018)
Antibacterial Khorshidian
Antifungal, Antibacterial Chandra
Antifungal, Antibacterial Negro
Antibacterial
Antifungal Ferdes (2018)
Antibacterial Ferdes (2018)
Antibacterial Ferdes (2018)
Antiparasitic, Antibacterial
Antibacterial Chew et al. (2022)
Antibacterial, Antiviral,
Antifungal
Antibacterial Savic
Antiviral, Antiparasitic,
Antibacterial
Antibacterial, Antiviral,
Antibiofilm
Antibacterial, Antifungal Memar
Antibacterial, Antifungal Sepahvand
⏎
Menezes
Ferdes (2018)
et al. (2022)
Chandra et al. (2017)
Choińska
Abedini et al. (2021)
et al. (2019)
Balahbib et al. (2021)
Gupta et al. (2021)
et al. (2017);
Ferdes (2018)
et al. (2022)
et al. (2018)
et al. (2017);
et al. (2021)
et al. (2021)
At the beginning of the 19th century, the actual drug discovery from the plant origin
was initiated, when a German scientist isolated painkillers and a sleep-inducing agent
TABLE 1.2 Plant-Based Secondary Metabolites as Anticancer Agents
Secondary Metabolites Source Chemical Nature Effective against the Type
Apigenin
Artemisinin
Artesunate
Berberine
Betulin
Camptothecin
Cryptotanshinone
Curcumin
Docetaxel
Emodin
Gingerol
Irinotecan
Kaempferol
Noscapine
Paclitaxel
Panaxadiol
Paradol
Podophyllotoxin
Quercetin
Resveratrol
Roscovitine
Salvicine
Shogaol
Sulforaphane
Matricaria chamomilla
Artemisia annua
Artemisia annua
Berberis vulgaris
Betula sp.
Camptotheca acuminate
Salvia prionitis
Curcuma longa
Taxus sp.
Aloe vera
Zingiber officinale
Camptotheca acuminate
Vitis vinifera slyvestris
Papaver somniferum
Taxus sp.
Panax ginseng
Zingiber officinale
Podophyllum sp.
Curcuma domestica, Cuscuta
reflexa, Daucus carota
Vitis vinifera slyvestris
Raphanus sativus
Salvia prionitis
Zingiber officinale
Brassica oleraceae
Flavone Breast, lung, liver Choudhury
Sesquiterpene lactone Lung Slezáková and Ruda-Kucerova (2017)
Sesquiterpene lactone Breast, lung, colon Liu
Alkaloid Breast, colon Xu et al. (2019)
Triterpene Breast, lung, colon Król et al. (2015)
Alkaloid Lung, pediatric FDA (2020)
Quinoid diterpene Breast, lung Wu
Diferuloyl methane Pancreas, breast Pastorelli et al. (2018)
Terpenoid Lung, ovarian and breast Seca and Pinto (2018)
Anthraquinone Lung, breast, liver Pecere
Hydroxy ketone Colorectal Danwilai et al. (2017)
Alkaloid Ovarian, lung, colorectal Wahid (2016)
Flavonoid Ovarian, pancreatic Kashyap
Pthalideisoquinoline Leukemia, lung, breast Tripathi et al. (2014)
Alkaloid Lung, ovarian, breast Moraes et al. (2017)
Triterpenoid saponin Colon Li et al. (2009)
Phenolic ketones Breast, colon Al-Abbasi et al. (2016)
Lignan Lymphomas, testicular Moraes et al. (2017)
Flavonol Gastric Tang et al. (2020); Khursheed et al.
Polyphenolic phytoalexin Colorectal, breast Malaguarnera (2019); Fan
Purine Lung, breast FDA (2020)
Quinone Breast, lung
Benzenoids Breast, colon Zhu et al. (2013)
Isothiocyanate Prostate, breast Chartoumpekis et al. (2020)
⏎
of Cancer
4
References
et al. (2013)
et al. (2011)
et al. (2016)
et al., (2000); Xing et al. (2015)
et al. (2017)
(2020)
et al. (2020)
Deng et al. (2011)
5
from opium and named morphium (morphine). He came up with a detailed paper based
on the isolation, structure, and pharmacological properties of opium. The discovery
of opium prompted the investigation of more medicinal plants. Consequently, in the
following decades of the 19th century, various natural products with bioactivity, mainly
the “alkaloid” class of chemicals, which includes atropine, caffeine, capsaicin, cocaine,
codeine, colchicine, nicotine, and quinine were isolated from natural resources. For the
rst time pharmaceutical industries were established by pharmacists who were trained in
the isolation of these compounds. H.E. Merck was the rst established pharmaceutical
company that initiated the isolation of morphine and other alkaloids in 1826. Among the
synthesis of natural compounds, salicylic acid was the rst compound to be synthesized in
the laboratory in 1853 (Chinou, 2008; Thirumurugan et al., 2018). After the discovery of
the drug from microbial resources, pure compounds took over the use of extracts and partly
puried extracts. Despite the advancement in chemistry and related disciplines during the
last few decades, therapeutic agents originating from natural products are still in high
demand.
Phytochemicals from the plant origin are usually classied as primary and secondary
metabolites.
It is normal for all plants to produce constituents as a result of their usual metabolic
activities. Primary metabolites are classified as those chemicals, which are essential for
the survival of plant cells. These include sugars, amino acids, fats, and nucleotides, which
are almost present in every type of cell in respective proportions. They have been identified in all species, families, and genera of plants since they are the key components in a
plant’s survival. They help in the production of polymers, considered to be an important
necessity of a plant. The biochemistry involved in these simple chemicals is distinguished
from the generation of other complex molecules formed as a result of divergent pathways
(Itokawa et al., 2008; Anulika et al., 2016).
Secondary metabolites constitute a class of compounds, which are produced and decomposed
and are necessary for the whole plant. They do not have any particular role in the primary
metabolism of the plant including growth, photosynthesis, and reproduction. They play a
critical role in chemical adaptation triggered due to different environmental stresses, and
chemical defense against microorganisms, insects, and other plants. The role of secondary
metabolites as pollinator attractants is another important characteristic that plays a vital
role in plant reproduction. These metabolites are used commercially as nutraceuticals,
fragrances, vegetable oils, spices, and medicinal drugs. Precisely secondary metabolites are
known as biologically active agents, which present higher quality but a lower quantity in
comparison with primary metabolites (Chinou, 2008; Thirumurugan et al., 2018).
6
The secondary metabolites’ synthesis occurs in distinct types of plant cells, unlike
primary metabolites. As their synthesis involves various developmental stages, it makes
their isolation and extraction more effortful. This class of phytochemicals extensively
varies from one plant to another. Each type of plant family, genus, or species synthesizes
its characteristic chemical class or a mixture of them (Chinou, 2008). These metabolites
have been classied into three major categories as terpenoids, phenolics, and nitrogen-
containing compounds.
T erpenoids are a chemical class of compounds made up of carbon and hydrogen entirely .
Analytically, terpenoids are produced by a ve-carbon building unit structure which leads
to the production of compounds having C5, C10, C15, C20, and up to C40 structural
skeletons. Terpenoids are dened as a broad class of natural products, synthesized by a
biosynthetic pathway based on mevalonate as a parent, comprising subgroups such as
isoprenoids and steroids. Terpenoids are further classied based on the building units such
as monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, carotenoids, and so on.
The occurrence of terpenoids is common in higher plants, algae, lichens, liverworts, and
mosses. Among the bioactive class of natural products, diterpenoids presented a wider
scope of biological activities (Itokawa et al., 2008; Anulika et al., 2016).
The second major chemical class of secondary metabolites includes phenolics. Phenolics
are aromatic compounds with the replacement of the hydroxyl group. The parent molecule
of these compounds is phenol but most of them are complex molecules and the complexity
is determined by the number of carbon atoms present in the basic skeleton. The derived
classes of phenol contain at least one or more chains such as salicylic acid, caffeic acids,
hydroxycinnamic acid, and so on. Phenolic compounds from the plant origin are produced
via two main biosynthetic pathways; either through shikimic acid, also known as benzoic
acid derivatives, lignans, coumarins, and so on, or through acetate, resulting in polyketides,
which develop by cyclization to products such as xanthones and quinines. The important
classes of phenolics isolated from plants are benzoquinones, phenolic acids, hydroxycin-
namic acids, xanthones, avonoids, lignans, and tannins. These phenolic compounds
possess potential medicinal value and are widely used as allelopathic substances, fungicidal
agents, antioxidants, and antimicrobial agents (Anulika et al., 2016).
Nitrogen-containing secondary metabolites are considered the most diversied class of
chemical compounds. These compounds may occasionally contain sulfur in their chemical
structure. Amino acids are divided into two main groups specically from plant origin such
as protein and nonprotein amino acids. Plant protein amino acids are important in carrying
out distinct extracellular and intracellular functions of the plant. They play a critical role
in guarding against possible predators and are usually stored in the seeds of plants. They
are essential in the human diet but some of them are toxic to humans as well. These
compounds have been utilized in drug development such as l-Dopa which is a therapeutic
agent for Parkinson’s disease. Among others, alkaloids are a group of nitrogen-containing
chemical compounds that exhibit potential pharmacological properties. The structure of
alkaloids is highly diversied from being very simple, complex and extremely complex
structures. They are classied based on the amino acids, a precursor of their synthesis.
They can be found mostly in the Solanaceae, Papaveraceae, Fabaceae, Rubiaceae, and
Berberidaceae families. They could be classied into ve major groups which include
7
pyridine and piperidine, tropine, quinoline, isoquinoline, and indole alkaloids (Chinou,
2008; Anulika et al., 2016).
1.2.2 MICROBIAL NATURAL PRODUCTS
Microbes-based natural products are moieties that are produced by microorganisms such as
bacteria, fungi, and actinomycetes. These are commonly used in medicine, agriculture, and
industry, and have a wide range of applications because of their diversified structure. The
majority of chemotherapeutic agents used in modern medicine are isolated from microorganisms. Studies on microbial biosynthetic diversity revealed huge reservoirs of natural
products, many of which are yet to be discovered (Milshteyn et al., 2014; Seal et al., 2018).
Drug classes based on microbes-derived natural products include antimicrobials,
antifungals, immunosuppressants, antitumor agents, and enzymes. Antibiotics and related
bioactive products derived from microorganisms have been opted for by human beings for
billions of years. These bioactive molecules are produced by microorganisms as a defense
mechanism and are utilized to suppress other microbial competitors, and they have been
extensively studied and utilized for their potential therapeutic uses (Seal et al., 2018).
Numerous secondary metabolites isolated from microbes possess signicant antimicrobial,
antitumor, and other biological potentials. These secondary metabolites, along with their
sources and biosynthetic origin are summarized in Tables 1.3–1.5.
Penicillin, one of the rst antibiotics produced by the fungus Penicillium was discovered
in 1928. The rise in the contemporary period of microbial-based therapeutics, mainly
antibiotics started in the 1940s and lasted for about 30 years. During this period, several
microbial-based medications, such as tetracycline, erythromycin, and streptomycin were
discovered and many of them are still in use today. However, the period was rather brief
due to the development of antibiotic resistance. Among pathogenic-resistant microbes,
the ESKAPE pathogen group, which includes Acinetobacter baumannii, Enterobacter
sp., Enterococcus faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa, and
Staphylococcus aureus are most common and concerned bacteria (Challinor and Bode,
2015). The second important class of fungal β-lactam antibiotics, cephalosporins were
discovered in 1943, about 15 years after the discovery of penicillin (Karwehl and Stadler,
2016). The fungal-based natural products including cephalosporins and penicillin were
found to be effective against Gram-positive bacteria, whereas partially synthetic derivatives
were found to be effective against resilient Gram-negative bacteria as well (Karwehl and
Stadler, 2016). Altogether, numerous antibiotics have originated from the genus Bacillus
such as lantibiotics, gramicidin, and bacteriocin. Another group of bacteria, myxobacteria,
soil-dwelling bacteria, acquires the largest genomes of all bacteria and is known to possess
an array of novel secondary metabolites. It is reported that more than 500 natural products
originated from terrestrial as well as marine Myxobacteria, including the rst derived
antibiotic, ambruticin in 1977 (Challinor and Bode, 2015).
Several antibiotics have been derived from Gram-positive bacteria, such as members
of actinomycetales which produced more than 500 antibiotics. Out of 500, 90% of the
antibiotics are produced solely by the genus Streptomyces. The discovery of streptomycin
TABLE 1.3 Microbes-Based Secondary Metabolites as Antimicrobial Agents
Secondary Metabolites Source Biosynthetic Origin References
Actinomycin
Adriamycin
Albomycin
Amphomycin
Amphotericin B
Avermectin
Bleomycin
Candicidin
Capreomycin
Cephalosporin
Chlorobiocin
Clavulanic acid (Augmentin)
Daptomycin
Daunorubicin
Epothilone
Erythromycin
Fusidic acid
Geldanamycin
Gentamicin
Josamycin
Kirromycin
Milbemycin
Mitomycin C
Monensin
Natamycin (pimaricin)
Streptomyces anulantus
Streptomyces peucetius
Streptomyces sp.
Streptomyces canus
Streptomyces nodosus
Streptomyces avermitilis
Streptomyces verticilus
Streptomyces sp.
Saccharothrix mutabilis
Cephalosporium acremonium
Streptomyces roseochromogenes
Streptomyces clavuligerus
Nonomuraea sp.
Streptomyces peucetics
Sorangium cellulosum
Saccharopolyspora erythraea
Fusidium coccineum
Streptomyces hygroscopicus
Micromonospora purpurea
Streptomyces narbonensis
Streptomyces collinus
Streptomyces hygroscopic
Streptomyces lavendulae Streptomyces
caespitosus
Streptomyces cinnamonesis
Streptomyces sp.
⏎
NRPS Charousová
PKS II Ikeda et al. (2014); Marinescu (2021)
Peptidyl-nucleoside Lin
NRPS Sharma et al. (2014)
PKS I Svahn et al. (2015)
PKS I Abokwidir and Fleischer (2015)
NRPS-PKS I Baltz (2011); Chopra and Dhingra (2021)
PKS I Králová
NRPS Dijkstra et al. (2018)
NRPS Hobson et al. (2021)
Aminocoumarine Katz and Baltz (2016)
Other Huttner
NRPS Sader et al. (2011)
PKS II Katz and Baltz (2016); Chopra and Dhingra (2021)
NRPS-PKS I Kimura
PKS I Challis (2014)
Terpine
PKS I Lamoth et al. (2015)
Aminoglycoside Bibb et al. (1978); Katz and Baltz (2016)
PKS I Dhawan et al. (2012)
NRPS-PKS I McHugh et al. (2022)
PKS I Niimi et al. (2022)
Quinone Katz and Baltz (2016); Pacios et al. (2021)
PKS I Mimouni et al. (2014)
PKS I Santonicola et al. (2017)
et al. (2019)
et al. (2020)
et al. (2020)
Hobson et al. (2021)
8
et al. (2019)
et al. (2021)
TABLE 1.3
Secondary Metabolites Source Biosynthetic Origin References
Neomycin
Oxytetracycline
Penicillin
Phosphomycin
Pleuromutalin
Polymyxin (D)
Rebeccamycin
Rifamycin
Ristocetin
Salinomycin
Spiramycin
Streptomycin
Streptothricin
Teicoplanin
Tetracenomycin
Tetracycline
Thiostrepton
Tylosin
Undecylprodigiosin
Viomycin
Virginiamycin
Notes: NRPS: Nonribosomal peptide synthetase; PKS: Polyketide synthase; RiPP: Ribosomally-synthesized and post-translationally-modified peptide.
(Continued)
Streptomyces fradiae
Streptomyces rimosus
Penicillium crysogenum
Streptomyces wedmorensis
Clitopilusscyphoides
Paenibacillus polymyxa
Lechevalieria aerocolonegenes
Amycolatopsis mediterranei
Amycolatopsis lurida
Streptomyces albus
Streptomyces ambofaciens
Streptomyces griseus
Streptomyces sp.
Actinoplanes teichomyceticus
Streptomyces glaucescens
Streptomyces rimous
Streptomyces azureus
Streptomyces fradiae
Streptomyces coelicolor
Streptomyces sp.
Streptomyces virginiae
Aminoglycoside
PKS II Payne et al. (2021)
NRPS Bachmann et al. (2014)
Phosphone Sherry and Howden (2018)
Diterpene Wang
NRPS Tietz and Mitchell (2016)
Alkaloid Desouky
PKS I Baltz (2014); Hiramine et al. (2021)
NRPS Katz and Baltz (2016)
PKS I Antoszczak and Huczyński (2019)
PKS I Qaisar
Aminoglycoside Breton and Reynolds (2013)
Aminoglycoside Dowgiallo
NRPS Koppen et al. (2019)
PKS II Sedeek et al. (2022)
PKS II Hobson et al. (2021)
RiPP Kim et al. (2019)
PKS I Cazer et al. (2020)
Other Ramesh et al. (2021)
NRPS Akbergenov et al. (2011)
NRPS, NRPS-PKS I Edrington et al. (2014)
Baltz (2007); Blanchard et al. (2016)
et al. (2022)
et al. (2022)
et al. (2017)
et al. (2022)
9
10
and streptothricin in the 1940s led to the discovery of several other candidates through
extensive screening. Nonetheless, it is predicted that only a small part of antibiotics have
been discovered from Streptomyces and there are many to discover yet (Challinor and
Bode, 2015).
TABLE 1.4 Microbes-Based Secondary Metabolites as Antitumor Agents
Secondary Metabolites Source Biosynthetic Origin References
Actinomycin
Adriamycin
Daunorubicin
Epothilone
Geldanamycin
Mitomycin C
Paclitaxel Several endophytic fungi Isoprenoid Bibb et al. (1978);
Rebeccamycin
Staurosporine
Streptozotocin
Tetracycline
Notes: NRPS: Nonribosomal peptide synthetase; PKS: Polyketide synthase.
TABLE 1.5
Secondary
Metabolites
Acarbose
Cyclosporin A
Lipstatinc (Xenical)
Lovastatin
Rapamycin
Notes: NRPS: Nonribosomal peptide synthetase; PKS: Polyketide synthase.
Microbes-Based Secondary Metabolites as Miscellaneous Agents
Streptomyces anulantus
Streptomyces peucetius
Streptomyces peucetics
Sorangium cellulosum
Streptomyces hygroscopicus
Streptomyces lavendulae
Lechevalieria aerocolonegenes
Streptomyces staurosporeus
Streptomyces achromogenes
Streptomyces rimous
Source Biosynthetic
Origin
Actinoplanes sp.
Tolypocladium inflatum
Streptomyces toxitricini
Aspergillus terrus
Streptomyces
hygroscopicus
Glycoside Antidiabetic Chopra and Dhingra
NRPS Immunomodulator
Fatty acyl-lactone Antiobesity Bérdy (2012)
PKS Cardiovascular Baltz (2006); Chopra
NRPS-PKS I Immunomodulator
NRPS
PKS II Ikeda et al. (2014);
PKS II Hendlin
NRPS-PKS I Kimura et al. (2020)
PKS I Lamoth et al. (2015)
Quinone Pacios et al. (2021)
Alkaloid Weissman (2015)
Alkaloid Baltz (2006)
Glucosamine nitrosourea
PKS II Hobson et al. (2021)
Pharmacological
Uses
⏎
Charousová et al. (2019)
Marinescu (2021)
et al. (1969)
Atanasov et al. (2015)
Bentley et al. (2002)
⏎
References
(2021); Singh
(2022)
Heeb et al. (2011)
and Dhingra (2021)
Bhanot et al. (2011);
Tasneen et al. (2012)
et al.
In addition to their medicinal properties, microbial-based natural products are also
utilized in the food and beverage industries. For example, the bacterium Lactobacillus
is used in the production of yogurt and other fermented dairy products, while the fungus,
Saccharomyces cerevisiae is used in the production of bread and beer. Overall, microbial-
based natural products have signicant potential for a variety of applications, and ongoing
research is continuing to identify new uses and potential therapeutic benets.
11
1.3 IMPORTANCE OF ANALYTICAL TECHNIQUES
1.3.1 A GLANCE AT EXTRACTION TECHNIQUES
The quantity of an active ingredient or desired secondary metabolites is always fairly
low in natural resources. The extensive lab use and time-consuming extraction and
isolation protocols have been the main obstacle in the practice of natural products as
drug candidates. Extraction is an initial step in the separation of desired natural products
from raw materials or natural resources. Some of the common extraction techniques
include solvent extraction, distillation methods, pressing and sublimation methods
(Zhang et al., 2018). The most applicable method is solvent extraction. Below given are
a few key factors which contribute to various phases involved in the isolation of natural
products.
1. Penetration of solvent into the solid matrix
2. Dissolution of solute
3. Diffusion of solute out of the solid matrix
4. Collection of isolated solute
Components that enhance the solubility and diffusion of the solute in the above phases
will promote the extraction process. Among other factors, the selection of solvent, raw
materials particle size, the solvent-to-solid ratio, duration, and temperature govern the
efciency of the extraction process (Brusotti et al., 2014; Zhang et al., 2018).
The isolation of a single molecular moiety is quite difcult from the complex mixture,
comprising fats, oils, avonoids, alkaloids, tannins, and glycosides. Both conventional and
modern techniques are available to isolate secondary metabolites from natural resources.
Conventional techniques such as maceration, percolation, distillation, and reux extraction are associated with multiple disadvantages, which include the consumption of excess
volume of solvents and longer time of extraction. On the contrary, modern technologies
including supercritical uid extraction, pressurized liquid extraction, electrical energy
extraction, microwave-assisted extraction, and ultrasound-assisted extraction have been
practiced to rule out difculties in extraction mainly the requirement of a larger volume of
solvents and long duration of extraction. With the advent of modern extraction techniques,
complications associated with conventional methods could be sorted out with enhanced
selectivity (Zhang et al., 2018; Najmi et al., 2022).
Chromatographic procedures are dened as a group of techniques utilized for the isolation of compounds from a mixture by continuous distribution between two phases, one of
which is the mobile phase and the other is the stationary phase. Several chromatographic
techniques employed for the isolation of desired compounds include paper chromatography ,
thin layer chromatography , gas chromatography , high-performance liquid chromatography ,
and liquid chromatography-mass spectrometry (Najmi et al., 2022).
There are certain other factors that inuence the concentration level and type of
secondary metabolites. These factors mainly cover plant age, altitude of the site, type of
soil, collection time, species, and so on. The chemical constitution of plants primarily relies
on the type of species as well as environmental factors (Visht and Chaturvedi, 2012).
12
1.3.2 MICROBIAL CULTURING TECHNIQUES
Another isolation methodology is culture-based techniques. In the culture-based technique,
bacteria are separated from their environment, cultured in monoculture fermentation
broths, followed by organic extraction, and then tested for bioactivity. Different factors
such as broth composition, pH, and temperature associated with the culture technique are
modified to increase the range of bacteria to be grown in the laboratory. As the efficiency
of easily attainable bacteria declines, scientists are focused on the advancement of culture
techniques and the employment of the activation of a silent gene cluster for previously
uncultured bacteria (Milshteyn et al., 2014). There are a few techniques, which have been
attempted to improve the culture of bacteria in a laboratory through:
1. Activation of cryptic metabolism
2. Exploitation of genetic/genomic sequence
3. Metagenomics, involving activation of silent pathways via host and cluster engineering or activation of the cryptic cluster in native hosts
4. Modification of host
It is important to take note that uncultured bacteria are primarily not “unculturable”
bacteria. That particular group of bacteria is not able to be cultured under the man-made
native habitat in the laboratory. Although multiple attempts have been made to culture
those bacteria, unfortunately, they are not able to grow well in native man-made habitats.
The in-vitro culture of bacteria encloses the bacteria to grow within a partially permeable
membrane, which allows the penetration of nutrients and growth factors but not cells.
Another method to promote the culture techniques includes the cultivation of a supporting
membrane suspended on a soil slurry. These improvements in the culture techniques
resulted in the identication of novel molecules, which could be utilized against specic
pathogens such as lassomycin, a ribosomal cyclic peptide with signicant efcacy against
Mycobacterium tuberculosis (Milshteyn et al., 2014).
1.3.3 OUTLOOK AND PERSPECTIVES IN NANOPARTICLES
The applications of natural products in drug development are limited despite of high
therapeutic values. There are certain restrictions associated with the application of natural
products in the development of a drug, which mainly includes bioavailability , solubility , and
target specificity . Bioavailability refers to the degree to which a molecule, such as a nutrient
or a drug, is absorbed and is available for the body to be utilized. The nature of a molecule
or drug plays a decisive act in the degree and rate of absorption when administered via any
pathway. Bioavailability can be influenced by other factors such as the presence of other
compounds that may enhance or inhibit the degree of absorption and the delivery systems.
Numerous approaches can be implemented to augment the bioavailability of natural
products including the use of novel delivery systems such as liposomes, transfersomes,
ethosomes, niosomes, phytosomes, nanoparticles, nanoemulsions, micelles, and many more
(Ansari et al., 2012). These nanodrug delivery systems (NDDS) possess an extraordinary