Aureus American Type Culture Collection Research Articles

Metabolic Comparison and Molecular Networking of Antimicrobials in Streptomyces Species.

Streptomyces are well-known for producing bioactive secondary metabolites, with numerous antimicrobials essential to fight against infectious diseases. Globally, multidrug-resistant (MDR) microorganisms significantly challenge human and veterinary diseases. To tackle this issue, there is an urgent need for alternative antimicrobials. In the search for potent agents, we have isolated four Streptomyces species PC1, BT1, BT2, and BT3 from soils collected from various geographical regions of the Himalayan country Nepal, which were then identified based on morphology and 16S rRNA gene sequencing. The relationship of soil microbes with different Streptomyces species has been shown in phylogenetic trees. Antimicrobial potency of isolates was carried out against Staphylococcus aureus American Type Culture Collection (ATCC) 43300, Shigella sonnei ATCC 25931, Salmonella typhi ATCC 14028, Klebsiella pneumoniae ATCC 700603, and Escherichia coli ATCC 25922. Among them, Streptomyces species PC1 showed the highest zone of inhibition against tested pathogens. Furthermore, ethyl acetate extracts of shake flask fermentation of these Streptomyces strains were subjected to liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis for their metabolic comparison and Global Natural Products Social Molecular Networking (GNPS) web-based molecular networking. We found very similar metabolite composition in four strains, despite their geographical variation. In addition, we have identified thirty-seven metabolites using LC-MS/MS analysis, with the majority belonging to the diketopiperazine class. Among these, to the best of our knowledge, four metabolites, namely cyclo-(Ile-Ser), 2-n-hexyl-5-n-propylresorcinol, 3-[(6-methylpyrazin-2-yl) methyl]-1H-indole, and cyclo-(d-Leu-l-Trp), were detected for the first time in Streptomyces species. Besides these, other 23 metabolites including surfactin B, surfactin C, surfactin D, and valinomycin were identified with the help of GNPS-based molecular networking.

Physicochemical analysis and anti-bacterial activity of rhizome of tumeric (Curcuma longa L.) vegetable plants

Curcuma longa L (Tumeric) a rhizomatous perennial herb belonging to the ginger family Zingiberaceae, was studied to evaluate its physicochemical properties and antibacterial activity against gram-positive and gram-negative bacteria. Two solvent extractions (Aqueous and Ethanol) were prepared from the rhizomes obtained from Makurdi, Benue State, Nigeria which were dried and ground into powder of mesh size of 0.2 mm in diameter. The physicochemical analysis showed a pH of 6.95, Iodine Value of 51.39, Refractive Index of 1.44 and Specific Gravity of 1.45 which imply moderate level of unsaturated fatty acids content and high antimicrobial activity. Its antibacterial evaluation against Staphylococcus aureus American Type Culture Collection (ATCC) 25923 (gram +ve) and Pseudomonas aeruginosa ATCC 29953 (Gram -ve) were carried out with the two extracts and Chloramphenicol as the control using agar well diffusion method. The antibiotic showed significantly higher inhibitory effect on the bacterial isolates than the aqueous extract (P<0.05). It also showed higher effect than the ethanol extract on S. aureus (P<0.05) but statistically equal effect on P. aeruginosa (P>0.05). The ethanol extract showed higher activity against the test organisms than the aqueous extract at P<0.05. The zones of inhibition for the aqueous extract ranged from 7.00 mm – 13.67 mm for S. aureus and 7.33 mm – 14.33 mm for P. aeruginosa and the ethanol extract, 13.33 mm – 19.00 mm and 15.00 mm – 13.00 mm for S. aureus and P. aeruginosa respectively. The Minimum Inhibitory Concentration was observed at 12.5 mg/mL in both cases. The antibacterial activity shown by C. longa may be due to the presence of phytochemicals such as Alkaloids, Steroids, Saponins, Flavonoids, Phenols and Tannins which were observed when the extract was analyzed phytochemically. C. longa showed potent activity against bacteria in this study and would make a more active and viable antibiotic.

Effect of post-synthesis betanin functionalized silver nanoparticles on the cellular oxidative mechanism and biofilm formation in Staphylococcus aureus

Eliciting oxidative stress and interference with biofilm formation by silver nanoparticles (AgNPs) comprise some of the postulated mechanisms of bacteria destruction. Plant extracts are commonly employed both as reducing agents and stabilizers of green-synthesized AgNPs. This yields a broad nanoparticle size distribution and unpredictable coating arising from diverse biomolecules and oxidation products in the final reaction mixture, which makes the comparison of different experiments exploiting green synthesised AgNPs as antimicrobial agents tricky. The current study synthesised citrate-capped silver nanoparticles (CtAgNPs) with a diameter of 37.9±8.6 nm functionalized via ligand exchange with betanin. Subsequently, the betanin silver nanoparticles (BtnAgNPs) ability to perturb the cellular oxidative stress defence mechanism of Staphylococcus aureus American Type Culture Collection (ATCC) 12600 and biofilm-forming properties were evaluated. Treatment with a minimum inhibitory concentration (MIC) of BtnAgNPs (12.5ppm) promoted reactive oxygen species accumulation and significantly reduced superoxide dismutase (SOD) and catalase activities. Furthermore, BtnAgNPs at sub-minimum inhibitory concentrations (SubMICs) to MIC range (0.39-12.5 ppm) inhibited the establishment of biofilms in a concentration-dependent manner. The study advocates for synthesis protocols that produce precise-sized nanoparticles followed by selective biomolecule functionalization for better antimicrobial efficacy comparative studies between AgNPs bearing different coatings in future experiments.

Comparative study of hydroethanolic extract of Terminalia mantaly on Staphylococcus aureus ATCC and Salmonella typhi

In the present work, antibacterial activity of a hydroethanolic extract of Terminalia mantaly was verified on two bacteriam strains Staphylococcus aureus American Type Culture Collection (ATCC) and Salmonella typhi in petri dishes by comparing the diameters of the different inhibition zones. The hydroethanolic extract of Terminalia mantaly was prepared with a solvent containing 70% ethanol and 30% distilled water. The Mueller-Hinton medium was poured into petri dishes and then the bacterial strains (Staphylococcus aureus ATCC and Salmonella typhi) were separately plated. Using the wells, the extract was introduced to record the diameters of the inhibition zone in order to assess the antibacterial activity. Oxacillin was used as a standard antibacterial. The results showed that the antibacterial activity is pronounced on Staphylococcus aureus ATCC compared to Salmonella typhi. These tests support the use of Terminalia mantaly against various bacterial diseases.

Isolation and Characterization of Halophilic Kocuria salsicia Strains from Cheese Brine.

Kocuria salsicia can survive in extreme environments and cause infections, including catheter-related bacteremia, in humans. Here, we investigated and evaluated the characteristics of nine K. salsicia strains (KS1–KS9) isolated from cheese brine from a farmstead cheese-manufacturing plant in Korea from June to December, 2020. Staphylococcus aureus American Type Culture Collection (ATCC) 29213 was used as a positive control in the growth curve analysis and biofilm-formation assays. All K. salsicia isolates showed growth at 15% salt concentration and temperatures of 15°C, 25°C, 30°C, 37°C, and 42°C. KS6 and KS8 showed growth at 5°C, suggesting that they are potential psychrotrophs. In the biofilm-formation analysis via crystal violet staining, KS6 exhibited the highest biofilm-forming ability at various temperatures and media [phosphate buffered saline, nutrient broth (NB), and NB containing 15% sodium chloride]. At 25°C and 30°C, KS3, KS6, and KS8 showed higher biofilm-forming ability than S. aureus ATCC 29213. The antimicrobial resistance of the isolates was evaluated using the VITEK® 2 system; most isolates were resistant to marbofloxacin and nitrofurantoin (both 9/9, 100%), followed by enrofloxacin (7/9, 77.8%). Five of the nine isolates (5/9, 55.6%) showed multidrug resistance. Our study reports the abilities of K. salsicia to grow in the presence of high salt concentrations and at relatively low temperatures, along with its multidrug resistance and tendency to form biofilms.

Characterization and validation of an alternative reference bacterium Korean Pharmacopoeia Staphylococcus aureus strain.

The National Culture Collection of Pathogens (NCCP) is a microbial resource bank in Korea that collects pathogen resources causing infectious disease in human and distributes them for research and education. The NCCP bank attempts to discover strains with various characteristics and specific purposes to provide diverse resources to researchers. Staphylococcus aureus American Type Culture Collection (ATCC) 6538P is used as a reference strain in the microbial assay for antibiotics in the Korean and in the United States Pharmacopoeias. We aimed to analyze domestically isolated microbial resources from the NCCP to replace the S. aureus reference strain. Staphylococcus aureus strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the VITEK-2 system and characterized by multilocus sequence typing, 16S rRNA sequencing, and antibiotic susceptibility testing. Several candidate strains had similar characteristics as the reference strain. Among them, the nucleotide sequence of the 16S rRNA region of NCCP 16830 was 100% identical to that of the reference strain; it was sensitive to six types of antibiotics and showed results most similar to the reference strain. A validity evaluation was conducted using the cylinder-plate method. NCCP 16830 presented valid results and had the same performance as ATCC 6538P; therefore, it was selected as an alternative candidate strain.

Ceftaroline In-vitro Activity against Methicillin Resistant Staphylococcal Isolates in a Rural Tertiary Healthcare Centre

Introduction: The emergence of Methicillin Resistant (MR) staphylococcal infections had led to fewer therapeutic options. Ceftaroline fosamil is the only cephalosporin approved by United States of America (USA) Food and Drug Administration (FDA) till now which has activity against MR staphylococcal isolates. Until now, studies on in-vitro activity of ceftaroline are limited. Aim: To know the susceptibility pattern of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Resistant Coagulase Negative Staphylococci (MRCoNS) against ceftaroline in a rural tertiary health care centre. Materials and Methods: The present cross-sectional study was conducted in a tertiary care hospital in rural part of Karnataka between two months (July and August 2019). A total of 50 consecutive, non repetitive clinical isolates of MRSA and MRCoNS were obtained. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The Minimum Inhibitory Concentration (MIC) of ceftaroline was detected using E-strips (Biomerieux). The CLSI breakpoints applied for the interpretation of ceftaroline MIC- Sensitive: ≤1 μg/mL; Susceptible Dose Dependent (SDD): 2-4 μg/ mL and resistant ≥8 μg/mL). Staphylococcus aureus American Type Culture Collection (ATCC) 29213 was used as a quality control. Statistical analysis was done using microsoft excel. Percentages were used in this study to analyse variables. Results: Out of 50 MR staphylococcal isolates, 10 (20%) were MRSA and 40 (80%) were MRCoNS. Of the MR staphylococcal isolates tested, 49 (98%) were sensitive to ceftaroline. The MIC 50 and MIC 90 for the 50 MR staphylococci was 0.25 μg/mL and 1 μg/mL, respectively. Conclusion: Ceftaroline demonstrated a potent in-vitro activity against MR staphylococci. So it can be used as an effective drug in the treatment of such infections.

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod.

In an effort to find new repurposed antibacterial compounds, we performed the screening of an FDA-approved compounds library against Staphylococcus aureus American Type Culture Collection (ATCC) 25923. Compounds were evaluated for their capacity to prevent both planktonic growth and biofilm formation as well as to disrupt pre-formed biofilms. One of the identified initial hits was fingolimod (FTY720), an immunomodulator approved for the treatment of multiple sclerosis, which was then selected for follow-up studies. Fingolimod displayed a potent activity against S. aureus and S. epidermidis with a minimum inhibitory concentration (MIC) within the range of 12–15 µM at which concentration killing of all the bacteria was confirmed. A time–kill kinetic study revealed that fingolimod started to drastically reduce the viable bacterial count within two hours and we showed that no resistance developed against this compound for up to 20 days. Fingolimod also displayed a high activity against Acinetobacter baumannii (MIC 25 µM) as well as a modest activity against Escherichia coli and Pseudomonas aeruginosa. In addition, fingolimod inhibited quorum sensing in Chromobacterium violaceum and might therefore target this signaling pathway in certain Gram-negative bacteria. In conclusion, we present the identification of fingolimod from a compound library and its evaluation as a potential repurposed antibacterial compound.

Physicochemical and antimicrobial properties of post-synthesis betanin and chitosan oligosaccharide functionalized silver nanoparticles

Size uniformity and defined surface coating are important parameters for the biological properties of silver nanoparticles (AgNPs). Green synthesis uses biomolecules either in pure form or plant extracts as both reductants and stabilizers yielding a wide size range and capping composed of oxidation products and biomolecules present in the reaction mixture. Herein, we used an established methodology, silver nitrate as the metal precursor, and sodium citrate and tannic acid for reduction and stabilization to produce weakly passivated citrate capped AgNPs (CtAgNPs). Inductively coupled plasma mass spectrometry was used to determine the total concentration of silver in the purified nanoparticles colloidal dispersion and results correlated with absorbance at localized surface plasmon resonance (LSPR) peak for quick estimation of silver concentration. The CtAgNPs were functionalized with chitosan oligosaccharide (mean Mn 5000) and betanin to yield chitosan and betanin capped AgNPs. Their biocidal properties were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 12,600. Citrate-stabilized AgNPs had a LSPR peak at 432 nm, mean core diameter of 37.9 ± 8.6 nm, and a monomodal distribution, and were roughly spherical. A slight red shift in LSPR peak was observed upon capping change. The minimum inhibitory concentration against S. aureus was 12.5 ppm Ag for all the nanoparticles. Our study advances the path of exploiting size reproducible techniques in AgNP synthesis, post-synthesis biomolecule functionalization for defined surface, and a clear procedure for estimating the concentration of Ag in assays. This is envisaged to encourage investigations with distinct sizes and capping for cross-comparison.

Efeitos antimicrobianos do fentanil e da bupivacaína: estudo in vitro

Study objectiveIn this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. DesignIn vitro prospective study. SettingUniversity Clinical Microbiology Laboratory. MeasurementsIn our study, in vitro antimicrobial effect of 0.05 mg.mL‐1 fentanyl citrate, 5 mg.mL‐1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18‐24 hours at 37°C. Main resultsIn terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24hours of incubation were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). ConclusionsAddition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate, which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

Antimicrobial effects of fentanyl and bupivacaine: an in vitro study

Study objectiveIn this study, we aimed to compare the antimicrobial effects of bupivacaine and fentanyl citrate and to reveal the impact on antimicrobial effect potential in the case of combined use. DesignIn vitro prospective study. SettingUniversity Clinical Microbiology Laboratory. MeasurementsIn our study, in vitro antimicrobial effect of 0.05 mg.mL-1 fentanyl citrate, 5 mg.mL-1 bupivacaine were tested against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 as Group F (Fentanyl Citrate) and Group B (Bupivacaine), respectively. S. aureus ATCC 29213, P. aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 25922 were cultured onto Mueller Hinton agar (Oxoid, UK) plates and Candida albicans ATCC 10231 were cultured onto Sabouraud dextrose agar (Oxoid, UK) plates for 18−24 hours at 37 °C. Main resultsIn terms of inhibition zone diameters, S. Aureus ATCC 29213, P. aeruginosa ATCC 27853, and C. albicans ATCC10231 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group F than Group B (p < 0.001). In terms of inhibition zone diameters, E. coli ATCC 25922, and K. pneumomiae ATCC 13883 values obtained after 12 and 24 hours of incubation ​​were significantly higher in Group B than Group F (p < 0.001, E. coli 12ª hour p = 0.005). ConclusionsAddition of fentanyl to Local Anesthetics (LAs) is often preferred in regional anesthesia applications in today's practice owing especially to its effect on decreasing the local anesthetic dose and increasing analgesia quality and patient satisfaction. However, when the fact that fentanyl antagonized the antimicrobial effects of LAs in the studies is taken into account, it might be though that it contributes to an increase in infection complications. When the fact that fentanyl citrate which was used in our study and included hydrochloric acid and sodium hydroxide as protective agents, broadened the antimicrobial effect spectrum of LAs, had no antagonistic effect and showed a synergistic antimicrobial effect against E. Coli is considered, we are of the opinion that the addition of fentanyl to LAs would contribute significantly in preventing the increasing regional anesthesia infection complications.

Assessment of In vitro Antibacterial Activity and Cytotoxicity Effect of Nigella sativa Oil.

Background:Methicillin resistance is a serious health concern since it has spread among Staphylococcus aureus and coagulase-negative Staphylococci (CoNS) that are frequent community and nosocomial pathogens worldwide. Methicillin-resistant strains are often resistant to other classes of antibiotics, making their treatment difficult. Nigella sativa oil is known to be active against Gram-positive cocci, yet its in vitro cytotoxicity is rarely investigated, is a proper and powerful candidate for treatment of methicillin-resistant isolates.Objectives:The aim of this study is to evaluate the in vitro antibacterial activity and cytotoxicity effect of N. sativa oil.Materials and Methods:The minimal inhibitory concentrations (MICs) of N. sativa oil were determined by broth microdilution method against four different American Type Culture Collection strains, 45 clinical isolates of methicillin-resistant S. aureus (MRSA), and 77 methicillin-resistant CoNS (MRCoNS). The effects of different dilutions (0.25 μg/mL, 0.5 μg/mL, and 1 μg/mL) of N. sativa oil on the proliferation of gingival fibroblasts were evaluated.Results:The MIC values of N. sativa oil against clinical isolates of Staphylococci were between <0.25 μg/mL and 1.0 μg/mL. Compared to the control group, there was no cytotoxic effect on the proliferation of the gingival fibroblasts.Conclusion:In the present study, the oil of N. sativa was very active against MRSA and MRCoNS and had no in vitro cytotoxicity at relevant concentrations. These findings emphasize that there is a requirement for further clinical trials on N. sativa oil for “safe” medical management of infections caused by methicillin-resistant Staphylococci.SUMMARY The minimal inhibitory concentration (MIC) values of Nigella sativa oil against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 standard strains were 0.5 μg/mL, 2 μg/mL, 64 μg/mL, and 64 μg/mL, respectivelyThe N. sativa oil showed an excellent antibacterial activity against clinical isolates of methicillin-resistant S. aureus and methicillin-resistant coagulase-negative Staphylococci with very low MIC range of <0.25–1.0 µg/mLThe N. sativa oil exhibited no cytotoxic effect on the proliferation of the gingival fibroblasts. Abbreviation used: ATCC: American Type Culture Collection; CLSI: Clinical and Laboratory Standards Institute; CoNS: Coagulase-negative Staphylococci; DMEM: Dulbecco's modified Eagle's medium; DMSO: Dimethyl sulfoxide; FBS: Fetal bovine serum; HGF: Human gingival fibroblast; MIC: Minimal inhibitory concentration; MRCoNS: Methicillin-resistant CoNS; MRSA: Methicillin-resistant S. aureus

Proteomic analysis of exoproteins expressed by enterotoxigenic Staphylococcus aureus strains

Pathogenic bacteria excrete a variety of virulence factors into extracellular medium and to the cell surface which have essential roles in the colonization and insurrection of the host cells, and thus reflect the degree of bacterial pathogenicity. For the exploration of virulence factors expressed in the secreted proteome fraction, different Staphylococcus aureus strains were analyzed using gel-based bottom-up proteomic approach. A total of 119 distinct proteins were identified for the enterotoxin gene cluster (egc) negative and seb gene positive S. aureus American Type Culture Collection (ATCC) 14458 strain by the use of one- and 2-DE based proteomics. Detailed analysis of enterotoxin region of the 2-D map confirmed, beside the highly expressed staphylococcal enterotoxin B (SEB), the presence of enterotoxin-like proteins SElK and SElQ previously predicted by genotyping (Sergeev et al.., J. Clin. Microbiol. 2004, 42, 2134-2143). Exoprotein patterns at the late-exponential (7 h) and stationary (24 h) phases of cellular growth show a high-level similarity in this region. Comparative analysis of enterotoxin region of five S. aureus strains including two clinical isolates (RIMD 31092 and A900322), a food derived strain (AB-8802) with highly prevalent egc positive operon and a nonenterotoxigenic reference strain (ROS) revealed the presence of different known enterotoxins and other virulence factors along with a number of core exoproteins. In addition, production of SElL (RIMD 31092) and SElP (A900322) was demonstrated for the first time at the protein level. Under the experimental conditions applied none of the enterotoxins encoded by the genes of egc operon was identified.

New indolicidin analogues with potent antibacterial activity.

Indolicidin is a 13-residue antimicrobial peptide amide, ILPWKWPWWPWRR-NH2, isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is active against a wide range of microorganisms and has also been shown to be haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of the present paper is two-fold. First, we examine the importance of tryptophan in the antibacterial activity of indolicidin. We prepared five peptide analogues with the format ILPXKXPXXPXRR-NH2 in which Trp-residues 4,6,8,9,11 were replaced in all positions with X = a single non-natural building block; N-substituted glycine residue or nonproteinogenic amino acid. The analogues were tested for antibacterial activity against both Staphylococcus aureus American type culture collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan is not essential in the antibacterial activity of indolicidin, and even more active analogues were obtained by replacing tryptophan with non-natural aromatic amino acids. Using this knowledge, we then investigated a new principle for improving the antibacterial activity of small peptides. Our approach involves changing the hydrophobicity of the peptide by modifying the N-terminus with a hydrophobic non-natural building block. We prepared 22 analogues of indolicidin and [Phe(4,6,8,9,11)] indolicidin, 11 of each, carrying a hydrophobic non-natural building block attached to the N-terminus. Several active antibacterial analogues were identified. Finally, the cytotoxicity of the analogues against sheep erythrocytes was assessed in a haemolytic activity assay. The results presented here suggest that modified analogues of antibacterial peptides, containing non-natural building blocks, are promising lead structures for developing future therapeutics.