scholarly journals The sandarazols are cryptic and structurally unique plasmid encoded toxins from a rare myxobacterium

2020 ◽  
Author(s):  
Fabian Panter ◽  
Chantal D. Bader ◽  
Rolf Müller

AbstractSoil dwelling bacteria such as myxobacteria defend themselves by using secondary metabolites to inhibit growth of competing microorganisms. In this work we describe a new plasmid found in Sandaracinus sp. MSr10575 named pSa001 spanning 209.7 kbp that harbors a cryptic secondary metabolite biosynthesis gene cluster (BGC). Activation of this BGC by homologous recombination mediated exchange of the native promoter sequence against a vanillate inducible system led to production and subsequent isolation and structure elucidation of novel secondary metabolites, the sandarazols A-G. The sandarazol structure contains intriguing features such as an α-chlorinated ketone, an epoxyketone and a (2R)-2-amino-3- (N,N-dimethylamino)-propionic acid building block. In depth investigation of the underlying biosynthetic machinery led to a concise biosynthetic model for the new compound family, including several uncommon biosynthesis steps. The chlorinated congener sandarazol C shows an IC50 value of 0.5 µM against HCT 116 cells and a MIC of 14 µM against Mycobacterium smegmatis, which points at the sandarazol’s potential function as defensive secondary metabolites or toxins. The sandara-zols’ BGC location on pSa001 is one of the very few example of large multimodular BGCs on a replicative plasmid, whose existence points at the mechanism of horizontal gene transfer events of entire multimodular BGCs to exchange chemical warfare capabilities between bacterial species.

2020 ◽  
Vol 19 (1) ◽  
pp. 129-136
Author(s):  
Kamel A. Saleh ◽  
Tahani H Albinhassan ◽  
Adel M. Al-Ghazzawi ◽  
Abdulrahman Mohaya ◽  
Ali A. Shati ◽  
...  

Purpose: To evaluate the bioactivity of hexane extract of S. fruticosa leaves against the cancer cell lines HepG2, MCF-7, and HCT-116, and to determine the chemical composition-function relationship. Methods: Using the liquid-liquid extraction method, the nonpolarL constituent compounds were isolated from the leaves. The cytotoxicity of the hexane extract was evaluated using an SRB assay. Mechanism of action was verified by observing the appearance of apoptotic bodies using fluorescence microscopy, while anti-proliferative activity was assayed via flow cytometry. Results: The results revealed that secondary metabolites in the hexane extract demonstrated the highest cytotoxicity, and thus anticancer activity, against HCT-116 cells, with an IC50 of 17.15 ± 0.78 mg/mL. The presence of apoptotic bodies indicate an ability to induce apoptosis. Flow cytometry results suggest that the secondary metabolites stalled the cell cycle at the G0/G1 phase. Conclusion: The results indicate that S. fruticosa hexane extract may be considered a potential new source of the anti-cancer compound, momilactone B. Keywords: Anticancer, Apoptosis, Colon Cancer, Liver cancer, Breast cancer, Liquid chromatography–mass spectrometry, Suaeda fruticose, Momilactone B


Author(s):  
Nilushi Indika Bamunu Arachchige ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. Emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly. Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays. Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds. Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria.


2021 ◽  
Vol 14 (2) ◽  
pp. 139
Author(s):  
Mohammad Azam Ansari ◽  
Sarah Mousa Maadi Asiri ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Ahmad Almatroudi ◽  
...  

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 470
Author(s):  
Mustafa Mohsen El-Zayat ◽  
Mostafa M. Eraqi ◽  
Hani Alrefai ◽  
Ayman Y. El-Khateeb ◽  
Marwan A. Ibrahim ◽  
...  

The current work aimed to synthesize selenium and zinc nanoparticles using the aqueous extract of Ephedra aphylla as a valuable medicinal plant. The prepared nanoparticles were characterized by TEM, zeta potential, and changes in the phytochemical constituents. Hence, the phenolic, flavonoid, and tannin contents were reduced in the case of the prepared samples of nanoparticles than the original values in the aqueous extract. The prepared extract of Ephedra aphylla and its selenium and zinc nanoparticles showed high potency as antioxidant agents as a result of the DPPH• assay. The samples were assessed as anticancer agents against six tumor cells and a normal lung fibroblast (WI-38) cell line. The selenium nanoparticles of Ephedra aphylla extract revealed very strong cytotoxicity against HePG-2 cells (inhibitory concentration (IC50) = 7.56 ± 0.6 µg/mL), HCT-116 cells (IC50 = 10.02 ± 0.9 µg/mL), and HeLa cells (IC50 = 9.23 ± 0.8 µg/mL). The samples were evaluated as antimicrobial agents against bacterial and fungal strains. Thus, selenium nanoparticles showed potent activities against Gram-negative strains (Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), Gram-positive strains (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis), and the fungal strain Candida albicans. In conclusion, the preparation of nanoparticles of either selenium or zinc is crucial for improved biological characteristics.


Medicines ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 27
Author(s):  
Kinjal Lakhani ◽  
Edgar A. Borrego ◽  
Karla G. Cano ◽  
Jonathan R. Dimmock ◽  
Renato J. Aguilera ◽  
...  

A series of novel N2-acryloylhydrazides 1a–m and a related series of compounds 6a–c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elcin Ozgur ◽  
Handan Kayhan ◽  
Gorkem Kismali ◽  
Fatih Senturk ◽  
Merve Sensoz ◽  
...  

Abstract Objectives The aim of this study is to investigate the effects of radiofrequency radiation (RFR) on apoptosis, proliferation, stress response, and inflammation markers in colorectal cancer cells. Methods We tested the effects of intermittent exposure to RFR at different frequencies on two different colorectal cancer cell lines; HCT-116 and DLD-1. Protein levels were subsequently analyzed by ELISA. Results RFR led to a decrease in P53, p-P53, p-P38, and p-IkB levels in HCT-116 cells, while leading to an increase in BAD, p-BAD, p-STAT3,NF-κB levels. Two thousand one hundred Megahertz of RFR altered the P53, BAD, and NF-ΚB expression in HCT-116 cells. P53, p-P53, BAD, p-BAD, NF-κB, p-NF-κB, p-P38, p-SAPK/JNK, p-STAT3, and p-IkB levels increased after exposure to RFR at 900 and 2,100 MHz in DLD-1 cells. Unlike HCT-116 cells, 1,800 MHz of RFR was reported to have no effect on DLD1 cells. Conclusions RFR increased apoptosis and inflammatory response in HCT116 cells, while lowering the active P38 and active P53 levels, which are indicators of poor prognosis in several cancers. Genetic differences, such as P53 mutation (DLD-1), are critical to the cell response to RFR, which explains the reason why scientific studies on the effects of RFR yield contradictory results.


2021 ◽  
Author(s):  
Wolfgang Hüttel ◽  
Michael Müller

Phenol coupling enzymes, especially laccases and CYP-enzymes create an enormous diversity of biarylic secondary metabolites in fungi, plants, and bacteria. The enzymes and the elucidation of the corresponding metabolic pathways are presented.


2013 ◽  
Vol 16 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Xin Zhao ◽  
So-Young Kim ◽  
Kun-Young Park
Keyword(s):  
Hct 116 ◽  

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