Screening Of Natural Products Research Articles

Structure-based pharmacophore mapping and virtual screening of natural products to identify polypharmacological inhibitor against c-MET/EGFR/VEGFR-2

Three receptor tyrosine kinases (RTKs), c-MET, EGFR, and VEGFR-2 have been identified as potential oncogenic targets involved in tumor development, metastasis, and invasion. Designing inhibitors that can simultaneously interact with multiple targets is a promising approach, therefore, inhibiting these three RTKs with a single chemical component might give an effective chemotherapeutic strategy for addressing the disease while limiting adverse effects. The in-silico methods have been developed to identify the polypharmacological inhibitors particularly for drug repurposing and multitarget drug design. Here, to find a viable inhibitor from natural source against these three RTKs, structure–based pharmacophore mapping and virtual screening of SN-II database were carried out. The filtered compound SN00020821, identified as Cedeodarin, from different computational approaches, demonstrated good interactions with all the three targets, c-MET/EGFR/VEGFR-2, with interaction energies of −42.35 kcal/mol, −49.32 kcal/mol and −44.83 kcal/mol, respectively. SN00020821displayed stable key interactions with critical amino acids of all the three receptors' kinase catalytic domains including “DFG motif” explored through the MD simulations. Furthermore, it also met the ADMET requirements and was determined to be drug-like as predicted from the Lipinski’s rule of five and Veber’s rule. Finally, SN00020821 provides a novel molecular scaffold that could be investigated further as a polypharmacological anticancer therapeutic candidate that targets the three RTKs. Communicated by Ramaswamy H. Sarma

A Matter of Timing: Rudy Tanzi on Alzheimer's Disease

A Matter of Timing: Rudy Tanzi on Alzheimer's Disease

Promoting Effects of Titanium Implants Coated with Dipterocarpus tuberculatus Extract on Osseointegration.

Titanium (Ti) is the most commonly used biomaterial for dental implants. When inserting Ti implants into jawbones, the main issue is the lack of strong bonding between the Ti implant and the host bone (osseointegration). Inspired by the outstanding adhesion performance of natural phenolic compounds on metal substrates and promoting effect for cell adhesion, we coated a natural plant extract, Dipterocarpus tuberculatus (MED), on Ti implants. We tested three groups of Ti plates and screw-shaped fixtures: nontreated Ti as commercially produced, ozone-treated Ti as commonly used surface modification for dental implants, and MED-coated Ti. Interestingly, the MED coating on the Ti plate preserved the surface wetting property for 20 days, whereas the hydrophilic wetting of ozone-treated Ti was readily transformed to hydrophobic within a day. Computerized tomography and histopathological analysis revealed that MED coating enhanced new bone tissue formation and regeneration. The gene expression level of integrin as a bone cell adhesion receptor and its downstream key regulators was significantly increased than that of ozone-treated Ti. Therefore, we suggest considering MED-mediated cell signaling pathways in screening natural products for cell adhesion and osseointegration, and MED as a suitable coating agent for improving Ti implantation.

Virtual screening of natural products inspired in-house library to discover potential lead molecules against the SARS-CoV-2 main protease

SARS-CoV-2, a new coronavirus emerged in 2019, causing a global healthcare epidemic. Although a variety of drug targets have been identified as potential antiviral therapies, and effective candidate against SARS-CoV-2 remains elusive. One of the most promising targets for combating COVID-19 is SARS-CoV-2 Main protease (Mpro, a protein responsible for viral replication. In this work, an in-house curated library was thoroughly evaluated for druggability against Mpro. We identified four ligands (FG, Q5, P5, and PJ4) as potential inhibitors based on docking scores, predicted binding energies (MMGBSA), in silico ADME, and RMSD trajectory analysis. Among the selected ligands, FG, a natural product from Andrographis nallamalayana, exhibited the highest binding energy of −10.31 kcal/mol close to the docking score of clinical candidates Boceprevir and GC376. Other ligands (P5, natural product from cardiospermum halicacabum and two synthetic molecules Q5 and PJ4) have shown comparable docking scores ranging −7.65 kcal/mol to −7.18 kcal/mol. Interestingly, we found all four top ligands had Pi bond interaction with the main amino acid residues HIS41 and CYS145 (catalytic dyad), H-bonding interactions with GLU166, ARG188, and GLN189, and hydrophobic interactions with MET49 and MET165 in the binding site of Mpro. According to the ADME analysis, Q5 and P5 are within the acceptable range of drug likeliness, compared to FG and PJ4. The interaction stability of the lead molecules with viral protease was verified using replicated MD simulations. Thus, the present study opens up the opportunity of developing drug candidates targeting SARS-CoV-2 main protease (Mpro) to mitigate the disease. Communicated by Ramaswamy H. Sarma

Screening of Natural Products and Small Molecules Uncovers Novel Coronavirus 1a/1b Frameshifting Inhibitors with Antiviral Properties

Screening of Natural Products and Small Molecules Uncovers Novel Coronavirus 1a/1b Frameshifting Inhibitors with Antiviral Properties

Phenotypic screening of compound libraries as a platform for the identification of antibiotic adjuvants: Identification of colistin adjuvants from a natural product library.

The identification of antibiotic adjuvants, small molecules that potentiate the activity of conventional antibiotics, provides an orthogonal approach to the development of new antibiotics in the fight against drug resistant bacterial infections. Methods to identify novel adjuvants could potentially aid efforts to overcome the increasing prevalence of resistance and stave off the onset of a "post-antibiotic era." Phenotypic whole cell screens allow for the identification of hits with the necessary properties to access their biomolecular target, and may also facilitate the discovery of novel adjuvant targets. A phenotypic screening platform is outlined, in which a natural product library was explored for activity with antibiotics from several mechanistically distinct classes against clinically important bacterial species. General approaches to delineating the mechanism of action of hit compounds identified from phenotypic screens are described, followed by specific approaches to uncovering the mechanism of action of the colistin adjuvants identified from the natural product screen.

Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach.

The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and control COVID-19 infections. The main protease (Mpro) is a salient enzyme in coronaviruses that plays a vital role in viral replication, making it a fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against the Mpro of SARS-CoV-2 using the Universal Natural Product Database (UNPD). As well, we studied the role of ionic liquids (ILs) on the structural stabilization of Mpro. Cholinium-based ILs are biocompatible and used for a variety of biomedical applications. Molecular docking was employed for the initial screening of natural products and ILs against Mpro. To predict the drug-likeness features of lead compounds, we calculated the ADMET properties. We performed MD simulations for the selected complexes based on the docking outcomes. Using MM/PBSA approaches, we conclude that compounds NP-Hit2 (−25.6 kcal mol−1) and NP-Hit3 (−25.3 kcal mol−1) show stronger binding affinity with Mpro. The hotspot residues of Thr25, Leu27, His41, Met49, Cys145, Met165, and Gln189 strongly interacted with the natural compounds. Furthermore, naproxenate, ketoprofenate, and geranate, cholinium-based ILs strongly interact with Mpro and these ILs have antimicrobial properties. Our findings will aid in the development of effective Mpro inhibitors.

Virtual screening of natural products against 5-enolpyruvylshikimate-3-phosphate synthase using the Anagreen herbicide-like natural compound library.

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes a reaction involved in the production of amino acids essential for plant growth and survival. EPSPS is the main target of glyphosate, a broad-spectrum herbicide that acts as a competitive inhibitor concerning phosphoenolpyruvate (PEP), which is the natural substrate of EPSPS. In the present study, we introduce a natural compound library, named Anagreen, which is a compendium of herbicide-like compounds obtained from different natural product databases. Herein, we combined the structure- and ligand-based virtual screening strategies to explore Anagreen against EPSPS using the structure of glyphosate complexed with a T102I/P106S mutant of EPSPS from Eleusine indica (EiEPSPS) as a starting point. First, ligand-based pharmacophore screening was performed to select compounds with a similar pharmacophore to glyphosate. Then, structure-based pharmacophore modeling was applied to build a model which represents the molecular features of glyphosate. Then, consensus docking was performed to rank the best poses of the natural compounds against the PEP binding site, and then molecular dynamics simulations were performed to analyze the stability of EPSPS complexed with the selected ligands. Finally, we have investigated the binding affinity of the complexes using free energy calculations. The selected hit compound, namely AG332841, showed a stable conformation and binding affinity to the EPSPS structure and showed no structural similarity to the already known weed EPSPS inhibitors. Our computational study aims to clarify the inhibition of the mutant EiEPSPS, which is resistant to glyphosate, and identify new potential herbicides from natural products.

Baiap3 regulates depressive behaviors in mice via attenuating dense core vesicle trafficking in subsets of prefrontal cortex neurons

Selective serotonin reuptake inhibitors (SSRIs) are effective first line therapies for treating depression, but are plagued by undesirable side effects and are not effective in all patients. Because SSRIs effectively deplete the neuronal releasable serotonin (5-HT) pool, gaining a deeper understanding of intracellular mechanisms regulating 5-HT pools can help us understand the shortcomings of SSRIs and develop more effective therapies. In this study, we found that BAIAP3 (brain-specific angiogenesis inhibitor 1-associated protein 3) is significantly downregulated in two mouse models of depression (the IR- and CUMS-induced depressive mouse models). In BAIAP3 downregulated models (in vitro and in vivo), we discovered that trafficking of dense core vesicle (DCV), organelles that store, transport and release cargo via exocytosis, was reduced. Accordingly, 5-HT exocytosis and levels in the synapse were lowered, causing defective post-synaptic neurotransmission. In a screen of natural products, we identified eucalyptol, the active components of Eucalyptus, as uniquely capable of increasing neuronal Baiap3 expression and elevate synaptic 5-HT levels. Moreover, eucalyptol treatment relieved depressive behavioral symptoms and restored serotonin levels in mice. Mechanistically, eucalyptol restores Baiap3 expression by reducing inhibitory microRNAs (miR-329, miR-362). These findings illuminate how Baiap3 depletion propagates neurotransmission dysfunction and point to eucalyptol as a novel agent for restoring serotonin exocytosis, suggesting potential for developing eucalyptol as a therapy for treating depression.

In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation.

ObjectiveTo explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses.MethodsIn this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2.ResultsAmong the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study.ConclusionNatural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2.Electronic Supplementary MaterialSupplementary materials (Appendixes 1–6) are available in the online version of this article at DOI: 10.1007/s11655-021-3504-5

Screening of Microbial Natural Products and Biological Evaluation of Trichomicin as Potential Anti-Cytokine Storm Agents.

COVID-19 has remained an uncontained, worldwide pandemic. Most of the infected people had mild symptoms in the early stage, and suddenly worsened or even died in the later stage which made the cytokine release syndrome (CRS) once again aroused people’s attention. CRS is an excessive immunity of the body to external stimuli such as viruses, bacteria, and nanomaterials, which can cause tissue damage, local necrosis or even death. Lipopolysaccharide (LPS) is one of the most effective CRS inducers, which can activate macrophages to release cytokines, including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL- 6 and chemokines. We used RT-PCR to detect the expression of representative cytokines in mouse and human cells at different concentrations of Trichomicin, Ebosin, and 1487B after LPS stimulation. The results showed that the expression of TNF-α, IL-1β, IL-6, and CXCL10 all increased after LPS stimulation. Among the various drugs, Trichomicin had the most obvious inhibitory effect on cytokine expression in vitro, and it was further verified in vivo that Trichomicin can improve the survival rate of mice stimulated with LPS. Finally, it was proved that Trichomicin inhibited the Stat3 and NF-κB pathways and reduced the phosphorylation of Stat3 and p65 after LPS stimulation, thereby inhibiting the response of macrophages to pro-inflammatory stimuli. The article clarified the inhibitory activity and mechanism of action of Trichomicin on CRS, and laid the foundation for the research on the anti-cytokine storm activity of microbial natural products.

Anti-bacterial activity of Corchorus olitorius L. and Acmella caulirhiza Del. on Streptococcus mutans, a cariogenic bacterium.

Dental caries remains a global oral health challenge with the prevalence reported as high as 66.7% in adults. Despite the use of modern medicines, the prevalence of dental caries remains high. This has led to extensive screening of natural products particularly from plants such as Corchorus olitorius L. and Acmella caulirhiza Del. for anti-cariogenic activity. To assess the anti-bacterial activity of Corchorus olitorius L. and Acmella caulirhiza Del. on Streptococcus mutans, a cariogenic bacteria. Plant materials of C. olitorius L. and A. caulirhiza Del. were extracted using diethyl ether, methanol, distilled water by cold maceration. Agar well diffusion method was used for sensitivity and susceptibility tests on S. mutans (ATCC 6519). The aqueous plant extract of C. olitorius L. and the ether plant extract of A. caulirhiza Del. had the highest zones of inhibition (16.10mm and 12.03mm respectively) at a concentration of 1000mg/ml. The lowest MIC and MBC were 62.5mg/ml and 250mg/ml respectively. Both C. olitorius L. and A. caulirhiza Del. as used in oral health practices have been found to have antibacterial activity against the cariogenic S. mutans. Further studies should be conducted to isolate bioactive compounds against S. mutans.

Impacts of Diverse Natural Products on Honey Bee Viral Loads and Health

Western honey bees (Apis mellifera), a cornerstone to crop pollination in the U.S., are faced with an onslaught of challenges from diseases caused by parasites, pathogens, and pests that affect this economically valuable pollinator. Natural products (NPs), produced by living organisms, including plants and microorganisms, can support health and combat disease in animals. NPs include both native extracts and individual compounds that can reduce disease impacts by supporting immunity or directly inhibiting pathogens, pests, and parasites. Herein, we describe the screening of NPs in laboratory cage studies for their effects on honey bee disease prevention and control. Depending on the expected activity of compounds, we measured varied responses, including viral levels, honey bee immune responses, and symbiotic bacteria loads. Of the NPs screened, several compounds demonstrated beneficial activities in honey bees by reducing levels of the critical honey bee virus deformed wing virus (DWV-A and-B), positively impacting the gut microbiome or stimulating honey bee immune responses. Investigations of the medicinal properties of NPs in honey bees will contribute to a better understanding of their potential to support honey bee immunity to fight off pests and pathogens and promote increased overall honey bee health. These investigations will also shed light on the ecological interactions between pollinators and specific floral food sources.

Evaluation of culture media and conditions of Amazonian filamentous fungi in an antimicrobial screening program

The rediscovery of bioactive compounds is a problem within natural product screening programs, because the chemical-genetic diversity of fungi is little explored and the standardization of cultivation conditions that allow obtaining new actives is critical in such programs. In this work, the impact of two solid mediums (rice and oats), a liquid medium (Czapeck broth) and different fermentation conditions were evaluated in order to explore new metabolic routes. Twelve filamentous fungi from Amazonian environments were used. UV-Vis spectrophotometry estimated the complexity of the extracts produced. The antimicrobial activity of the extracts was evaluated against an isolate of each Escherichia coli strain, Salmonella sp. and Staphylococcus aureus. Solid media proved to be more promising, as they allowed a wider range of active metabolites to be obtained. The oat medium provided a greater variety of metabolites, but due to the great complexity of the extracts obtained, the separation procedures were considerably more complex than for rice. Together, the rice culture medium and the use of 39 days of fermentation proved to be more promising conditions than the liquid medium normally used in screening programs in Brazil. The cultivation of Penicillium maximae (isolated for the second time in Brazilian territory) in solid medium provided the production of active fractions against E. coli in bioautography. In this study, it was observed that different fermentation conditions in solid culture are considerably promising in the search for bioactive natural products.

Application of microfluidic chips in anticancer drug screening.

With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years’ progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.

Research Profile: Dr. Jeevan K. Prasain

Dr. Jeevan K. Prasain is an associate professor of pharmacology and toxicology at the University of Alabama at Birmingham. His current research focuses on delineation of unconventional cyclooxygenase (Cox)-independent prostaglandin (PG) synthesis mechanism, mass spectrometry-based metabolomics/lipidomics, biological activity, and uptake and metabolisms of dietary botanicals in vitro and in vivo. Dr. Prasain received his MSc in chemistry from Tribhuvan University located in Kathmandu, Nepal and went on to obtain his PhD in Japan from the Toyama Medical and Pharmaceutical University in pharmaceutical sciences. During his PhD tenure, he devoted much of his studies to natural product chemistry resulting in the discovery of several novel bioactive diarylheptanoids, subjects he went on to publish in several papers. After the completion of his PhD, he was awarded the Canadian Government Visiting Fellowship at the Biotechnology Research Institute (BRI) in Montreal, Canada to pursue postdoctoral research. During his time at BRI, Dr. Prasain was involved in drug discovery and high throughput screening of bioactive natural products from natural product libraries and their analysis by tandem mass spectrometry. Through this research, Dr. Prasain later went on to be a recipient of a Science and Technology Award at RIKEN in Tokyo Japan where he developed a mass spectrometry method for analysis of antibiotic cytochalasins. Based on his experiences in natural products research, he developed a great interest in dietary polyphenols in the promotion of health and prevention of chronic disease. Dr. Prasain joined the University of Alabama at Birmingham (UAB) as a postdoctoral fellow with Dr. Stephen Barnes in 2001, where he was later promoted to Assistant Professor in 2003. One of his research focuses was on the understanding of antidiabetic effects of puerarin, an isoflavone C-glucoside from Kudzu root and its metabolism and bioavailability. Kudzu root is well-known in traditional Chinese medicine, and various kudzu root based dietary supplements are available in the US market. Prasain's lab, in collaboration with Dr. Elias Meezan, also at UAB, demonstrated that puerarin treatment significantly improves glucose tolerance in C57 BL/6J ob/ob mice, an animal model of Type 2 diabetes mellitus. Specifically, puerarin blunts the rise in blood glucose levels after i.p. administration of glucose. Prasain et al. also found that in contrast to its O-glucoside isomer daidzin, puerarin is essentially absorbed without undergoing metabolism and is excreted in the urine mainly as an unchanged parent. In addition, in collaboration with Dr. Clinton Grubbs at UAB on the role of cranberry juice in bladder cancer prevention in animals, Prasain et al. demonstrated that commercially available cranberry juice concentrate can prevent urinary bladder cancers dose-dependently in N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) induced bladder carcinogenesis in rats when compared to the control group. This study also indicated that cranberry compounds once ingested reach the urinary bladder and concentrate in the urine in either the intact or in the metabolized forms and may prevent against the progression of carcinogenesis. This is because bladder cancers occur almost exclusively in the bladder epithelium, which is directly exposed to the urine stored in the bladder. In 2009, Dr. Prasain received an NIH R21 funding for investigating urinary metabolites of cranberry that protect against bladder cancer. The primary focus of this project was to understand what cranberry metabolites stored in the bladder are bioavailable and which metabolites are responsible against bladder carcinogenesis. The other focus of Dr. Prasain's lab is in the area of lipidomics, particularly profiling and characterizing PGs and other signaling lipids using tandem mass spectrometry. Using a combination of genetics, microinjection, and mass spectrometry, the late Dr. Michael Miller's and Dr. Prasain's labs discovered that C. elegans oocytes secrete sperm attractants F-series PGs derived from polyunsaturated fatty acid precursors. This NIH funded research led to an unanticipated discovery that C. elegans and mice generate specific F-series PGs without Cox enzymes. Over the past several years, much of the Dr. Prasain's lab effort has been to identify genes essential for Cox-independent PG synthesis and the signaling mechanisms that regulate PG functions in reproductive biology. The authors declare no conflict of interest.

Taspine is a natural product that suppresses P2X4 receptor activity via phosphoinositide 3‐kinase inhibition

P2X4 is a ligand-gated cation channel activated by extracellular ATP involved in neuropathic pain, inflammation and arterial tone. Natural products were screened against human or mouse P2X4 activity using fura-2 loaded 1321N1 cells for measurement of intracellular Ca2+ responses. Whole-cell currents were measured by patch clamp. Human primary macrophage chemokine release was used to assess effect of taspine on inflammatory cell function. An enzymatic assay was performed to assess the effect of taspine on recombinant PI3-kinase. A natural product screen identified taspine as an inhibitor of human P2X4 activity. Taspine inhibits human and mouse P2X4-mediated Ca2+ influx in 1321N1 cells expressing receptors but lacked activity at human P2X2, P2X3, P2X2/3 and P2X7 receptors. Taspine inhibited the maximal response at human and mouse P2X4 but effective on ATP potency. Taspine has a slow onset rate (~15 min for half-maximal inhibition), irreversible over 30 min of washout. Taspine inhibits P2X4-mediated Ca2+ signalling in mouse BV-2 microglia cells and human primary macrophage. Taspine inhibited P2X4-mediated CXCL5 secretion in human primary macrophage. Taspine reversed ivermectin-induced potentiation of P2X4 currents in 1321N1 stably expressing cells. The PI3-kinase inhibitor LY294002 mimicked the properties of taspine on P2X4-mediated Ca2+ influx and whole-cell currents. Taspine directly inhibited the enzymatic activity of recombinant PI3-kinase in a competitive manner. Taspine is a novel natural product P2X4 receptor inhibitor, mediating its effect through PI3-kinase inhibition rather than receptor antagonism. Taspine can inhibit the pro-inflammatory signalling by P2X4 in human primary macrophage.

Natural-Product-Based Solutions for Tropical Infectious Diseases.

About half of the world's population and 80% of the world's biodiversity can be found in the tropics. Many diseases are specific to the tropics, with at least 41 diseases caused by endemic bacteria, viruses, parasites, and fungi. Such diseases are of increasing concern, as the geographic range of tropical diseases is expanding due to climate change, urbanization, change in agricultural practices, deforestation, and loss of biodiversity. While traditional medicines have been used for centuries in the treatment of tropical diseases, the active natural compounds within these medicines remain largely unknown. In this review, we describe infectious diseases specific to the tropics, including their causative pathogens, modes of transmission, recent major outbreaks, and geographic locations. We further review current treatments for these tropical diseases, carefully consider the biodiscovery potential of the tropical biome, and discuss a range of technologies being used for drug development from natural resources. We provide a list of natural products with antimicrobial activity, detailing the source organisms and their effectiveness as treatment. We discuss how technological advancements, such as next-generation sequencing, are driving high-throughput natural product screening pipelines to identify compounds with therapeutic properties. This review demonstrates the impact natural products from the vast tropical biome have in the treatment of tropical infectious diseases and how high-throughput technical capacity will accelerate this discovery process.

A multi-bioassay integrated approach to assess antifouling potential of extracts from the Mediterranean sponge Ircinia oros

The phylum Porifera and their symbionts produce a wide variety of bioactive compounds, playing a central role in their ecology and evolution. In this study, four different extracts (obtained by non-polar and semi-polar extraction methodologies) of the Mediterranean sponge Ircinia oros were tested through a multi-bioassay integrated approach to assess their antifouling potential. Tests were performed using three common species, associated with three different endpoints: the marine bacterium Aliivibrio fischeri (inhibition of bioluminescence), the marine diatom Phaeodactylum tricornutum (inhibition of growth), and different development stages of the brackish water serpulid Ficopomatus enigmaticus (gametes: sperm motion, vitality inhibition and cellular damage; larvae: development; adults: AChE (acetylcholinesterase)-inhibitory activity). The effects of extracts were species specific and did not vary among different extraction methodologies. In particular, no significant reduction of bioluminescence of A. fischeri was observed for all tested samples. By contrast, extracts inhibited P. tricornutum growth and had toxic effects on different F. enigmaticus’ developmental stages. Our results suggest that the proposed test battery can be considered a suitable tool as bioactivity screening of marine natural products.

Phenotypic screening system using three-dimensional (3D) culture models for natural product screening.

Recent progress in three-dimensional (3D) cell culture systems has attracted much attention in the fields of basic life science and drug development. Newly established methods include 3D co-culture, spheroid culture, and organoid culture; these methods enable more human tissue-like culture and have largely replaced traditional two-dimensional (2D) monolayer culture. By combining 3D culture methods with high-content imaging analysis, it is possible to obtain diverse and convincing data even during initial screening (which requires rapid and easy operating procedures). Until recently, 3D culture methods were considered expensive, time-consuming, complex, and unstable. However, by exploiting the self-assembling nature of cells and adding several technical improvements, we have developed several phenotypic screenings aimed at discovering anticancer compounds.