Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222

BacSp222 is a multifunctional peptide produced by Staphylococcus pseudintermedius 222. This 50-amino acid long peptide belongs to subclass IId of bacteriocins and forms a four-helix bundle molecule. In addition to bactericidal functions, BacSp222 possesses also features of a virulence factor, manifested in immunomodulatory and cytotoxic activities toward eukaryotic cells. In the present study, we demonstrate that BacSp222 is produced in several post-translationally modified forms, succinylated at the ε-amino group of lysine residues. Such modifications have not been previously described for any bacteriocins. NMR and circular dichroism spectroscopy studies have shown that the modifications do not alter the spatial structure of the peptide. At the same time, succinylation significantly diminishes its bactericidal and cytotoxic potential. We demonstrate that the modification of the bacteriocin is an effect of non-enzymatic reaction with a highly reactive intracellular metabolite, i.e., succinyl-coenzyme A. The production of succinylated forms of the bacteriocin depends on environmental factors and on the access of bacteria to nutrients. Our study indicates that the production of succinylated forms of bacteriocin occurs in response to the changing environment, protects producer cells against the autotoxicity of the excreted peptide, and limits the pathogenicity of the strain.

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Traditional varieties and wild pear from Serbia: A link among antioxidant, antidiabetic and cytotoxic activities of fruit peel and flesh

Botanica Serbica ◽

10.2298/botserb2102203o ◽

2021 ◽

Vol 45 (2) ◽

pp. 203-213

Author(s):

Mariana Oaldje-Pavlovic ◽

Ana Alimpic-Aradski ◽

Aleksandra Savic ◽

Smiljana Jankovic ◽

Milena Milutinovic ◽

...

Keyword(s):

Pyrus Communis ◽

Cytotoxic Activities ◽

Commercial Variety ◽

Pear Fruit ◽

Cytotoxic Potential ◽

Fruit Peel ◽

Methanolic Extracts ◽

Pathological Conditions ◽

Prevention And Treatment ◽

Fruit Part

This study was aimed at evaluating the antioxidant and antidiabetic activities of methanolic extracts of peel, flesh and mixed peel, and flesh, as well as the cytotoxic activity of mixed peel and flesh extracts obtained from fruits of six traditional pear varieties (Vidovaca, Lubenicarka, Karamanka, Jeribasma, Loncara and Takisa), one commercial variety (Williams Bartlett) and a wild pear (Pyrus communis) from Serbia. The tested extracts showed strong antioxidant activity regarding the prevention of ?-carotene bleaching and high ?-glucosidase inhibition, and no significant cytotoxic potential, with the exception of the Williams Bartlett and Pyrus communis extracts. Overall, the most potent fruit part was shown to be the peel. The most active variety in all of the applied antioxidant and antidiabetic assays was Takisa, while the wild pear, P. communis, was the most effective in inhibiting the proliferation of cancer cells. In conclusion, several methanolic extracts of pear fruit are promising candidates for further studies regarding the prevention and treatment of pathological conditions associated with the effects of oxidative stress, such as diabetes and even colorectal cancer.

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Cytotoxic Activity of tropane alkaloides of Species of Erythroxylum

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210119123409 ◽

2021 ◽

Vol 21 ◽

Author(s):

José Fernando Araújo Neto ◽

Erika Maria de Oliveira Ribeiro ◽

Ademir Evangelista do Vale ◽

Jorge Maurício David ◽

Juceni Pereira de Lima David

Keyword(s):

Natural Products ◽

Cytotoxic Activity ◽

Screening Program ◽

Evaluation Studies ◽

Tropane Alkaloids ◽

Chemotherapeutic Agents ◽

In Vitro Tests ◽

Cytotoxic Activities ◽

Cytotoxic Potential

: Erythroxylaceae is a family composed of four genera being Erythroxylum the only one represented in the Neotropical region. Chemical studies indicate the presence of alkaloids, terpenes, flavonoids and phenolic compounds as main compounds. The incorporation of cytotoxic activity assays of natural products using cell cultures assists in the selection of potential chemotherapeutic agents. In this work we describe a revision of the cytotoxicity evaluation studies performed with extracts and/or pure substances obtained from Erythroxylum species through an integrative review. We have found studies that evaluated the cytotoxic activity of 21 species of Erythroxylum against 45 different cell lines, the analysis of the chemical composition of these species shows that the metabolites present in each species influence the cytotoxic potential of them, especially the presence of disubstituted tropane alkaloids species with the highest cytotoxic potential. MTT and Sulforrodamine B assays were the main in vitro tests used for the evaluation of the cytotoxic activities. From the total of species, less than 10% of the Erythroxylum species have already been evaluated for the cytotoxic activity, four of them showed high cytotoxic activity according to with the criteria of the NCI plant screening program. Thus, this genus represents a potential source of natural products with antitumor activity.

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Chemical composition, anti-Trypanosoma cruzi and cytotoxic activities of the essential oil from green fruits of Protium ovatum (BURSERACEAE)

Revista Brasileira de Fruticultura ◽

10.1590/0100-29452018794 ◽

2018 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Elisângela Barbosa Borges Estevam ◽

Cássia Cristina Fernandes Alves ◽

Viviane Rodrigues Esperandim ◽

Cristiane de Melo Cazal ◽

Alex Fonseca Souza ◽

...

Keyword(s):

Mass Spectrometry ◽

Chemical Composition ◽

Essential Oil ◽

Trypanosoma Cruzi ◽

Neglected Tropical Disease ◽

Cytotoxic Activities ◽

Cytotoxic Potential ◽

Novel Drugs ◽

Antiparasitic Drugs ◽

First Time

Abstract Chagas disease is a major neglected tropical disease caused by Trypanosoma cruzi. It has been treated with the antiparasitic drugs nifurtimox and benzonidazole, which cause several side effects. The market for natural products has considerably grown lately and the use of plants has become an alternative to the development of novel drugs to cure the disease. Therefore, this study aimed at describing the chemical analysis of the essential oil from green fruits of Protium ovatum and evaluating their trypanocidal and cytotoxic potential. The essential oil was obtained by Clevenger hydrodistillation whereas its chemical composition was determined by gas chromatography coupled to mass spectrometry (GC-MS). The major compounds found in the essential oil from green fruits of P. ovatum were ß-myrcene (62.0 %), a-pinene (11.3 %) and limonene (7.3 %). To the best of our knowledge, this was the first time that the chemical composition of the essential oil from green fruits of P. ovatum was described. Results showed that the essential oil had strong trypanocidal activity against trypomastigote forms of theY strain of Trypanosoma cruzi (IC50 = 1.2 µg/mL). In addition, the essential oil from green fruits of P. ovatum did not display cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 550.3 µg/mL). As a result, it is an excellent option for the development of novel antiparasitic drugs.

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Synthesis and in vitro Biological Activity of New 4,6-Disubstituted 3(2H)-Pyridazinone-acetohydrazide Derivatives

Zeitschrift für Naturforschung C ◽

10.1515/znc-2012-5-604 ◽

2012 ◽

Vol 67 (5-6) ◽

pp. 257-265

Author(s):

Murat Sukuroglu ◽

Tijen Onkol ◽

Fatma Kaynak Onurdağ ◽

Gulsen Akalın ◽

M. Fethi Şahin

Keyword(s):

Biological Activity ◽

Antimicrobial Activities ◽

Cytotoxic Activities ◽

Gram Negative Bacteria ◽

Gram Negative ◽

E Coli ◽

Preliminary Results ◽

H Nmr ◽

Pyridazinone Derivatives

New 3(2H)-pyridazinone derivatives containing a N’-benzyliden-acetohydrazide moiety at position 2 were synthesized. The structures of these newly synthesized compounds were confi rmed by IR, 1H NMR, and MS data. These compounds were tested for their antibacterial, antifungal, antimycobacterial, and cytotoxic activities. The compounds 2-[4-(4-chlorophenyl)- 6-(morpholin-4-yl)-3-oxo-(2H)-pyridazin-2-yl]-N’-(4-tert-butylbenzyliden)acetohydrazide and 2-[4-(4-chlorophenyl)-6-(morpholin-4-yl)-3-oxo-(2H)-pyridazin-2-yl]-N’-(4-chlorobenzyliden) acetohydrazide exhibited activity against both Gram-positive and Gram-negative bacteria. Most of the compounds were active against E. coli ATCC 35218. The preliminary results of this study revealed that some target compounds exhibited promising antimicrobial activities

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2-Hydroxy-luisol A, a New Quinone-derived Tetraol from a Marine Streptomyces sp. and Oxidation Products of Luisol A*

Zeitschrift für Naturforschung B ◽

10.1515/znb-2011-0611 ◽

2011 ◽

Vol 66 (6) ◽

pp. 629-s642 ◽

Cited By ~ 2

Author(s):

Serge Fotso ◽

Clarisse B. Fotso-Fondja Yao ◽

Elisabeth Helmke ◽

Hartmut Laatsch

Keyword(s):

Biological Activity ◽

2D Nmr ◽

Oxidation Products ◽

Published Data ◽

Cytotoxic Activities ◽

Streptomyces Sp ◽

Jones Reagent ◽

Marine Streptomyces ◽

Swern Oxidation

In addition to luisol A (1a), luisol B (2), and aloesaponarin II, the marine streptomycete B7617 produced a new derivative of 1a, 2-hydroxy-luisol A (1b). In an attempt to increase the biological activity, luisol A (1a) was oxidized and delivered with Jones reagent or by Swern oxidation the derivatives 3a/3b and 4a/4b, respectively, but none of these compounds showed antimicrobial or cytotoxic activities. All structure elucidations are based on 2D NMR analyses or were derived by comparison with published data.

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Roles of lysine residues and N-terminal α-amino group in membrane-damaging activity of Taiwan cobra cardiotoxin 3 toward anionic and zwitterionic phospholipid vesicles

Toxicon ◽

10.1016/j.toxicon.2009.07.032 ◽

2010 ◽

Vol 55 (2-3) ◽

pp. 256-264 ◽

Cited By ~ 6

Author(s):

Yi-Ling Chiou ◽

Pei-Hsiu Kao ◽

Wen-Hsin Liu ◽

Shinne-Ren Lin ◽

Long-Sen Chang

Keyword(s):

Phospholipid Vesicles ◽

Amino Group ◽

Lysine Residues

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The reaction of 2,4,6-trinitrobenzene sulfonic acid with pancreatic elastase

Canadian Journal of Biochemistry ◽

10.1139/o70-194 ◽

1970 ◽

Vol 48 (11) ◽

pp. 1249-1259 ◽

Cited By ~ 5

Author(s):

Leticia Rao ◽

T. Hofmann

Keyword(s):

Rate Constant ◽

Sulfonic Acid ◽

Ph Dependence ◽

Order Rate Constant ◽

Trinitrobenzene Sulfonic Acid ◽

Amino Group ◽

Tyrosine Residues ◽

Inactivation Rate Constant ◽

Lysine Residues ◽

Ph Range

The reaction of elastase with trinitrobenzene sulfonic acid was investigated in the pH range 9–12. Elastase was found to be inactivated by 2,4,6-trinitrobenzene sulfonic acid. The pH dependence of the pseudo first-order inactivation rate constant showed a pK of 10.3 and gave a Hill plot coefficient of 1.15. Trinitrophenol did not inactivate the enzyme. These results indicate that the inactivation is due to the covalent reaction of trinitrobenzene sulfonic acid with a single group in the enzyme. This group is not the N-terminal since the loss of N-terminal valine was considerably slower than the loss of activity at pH 10.5. The inactivation of elastase with 2,4-dinitrofluorobenzene also showed no correlation with the loss of the N-terminal. When the enzyme was exhaustively treated and fully inactivated with trinitrobenzene sulfonic acid at pH 10.5, the N-terminal valine and two out of three lysine residues were trinitrophenylated. No evidence for the loss of histidine was found. One of the tyrosine residues may be trinitrophenylated as judged from the molar extinction of the trinitrophenylated protein, but it has not been possible to isolate a trinitrophenylated tyrosine-containing peptide. The results can be interpreted in one of two ways: (a) trinitrophenylation of a group with a pK of 10.3, not involved in the activity, inactivates because the introduction of the trinitrophenyl residue causes a denaturation of the enzyme; or (b) a group with a pK of 10.3 controls the active conformation of the enzyme. The results do not exclude the possibility that the N-terminal plays an important role in the activity of the enzyme. Below pH 10.5 the reactivity of the N-terminal is low, indicating that it is buried.At pH 9.0 only the ε-amino group of lysine in position 224 reacted with trinitrobenzene sulfonic acid and full activity was retained. The second-order rate constant for the trinitrophenylation of this group was 25 times higher than that of the ε-amino group of the α-N-benzoyllysine.

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Anthelmintic and Cytotoxic Activities of Two Medicinal Plants: Polygonum viscosum and Aphanamixis polystachya Growing in Bangladesh

Journal of Scientific Research ◽

10.3329/jsr.v6i2.17299 ◽

2014 ◽

Vol 6 (2) ◽

pp. 339-345 ◽

Cited By ~ 3

Author(s):

M. N. Amin ◽

M. S. Majumder ◽

M. M. R. Moghal ◽

S. Banik ◽

A. Kar ◽

...

Keyword(s):

Methanolic Extract ◽

Anthelmintic Activity ◽

Cytotoxic Activities ◽

Dependent Manner ◽

Reference Standard ◽

Cytotoxic Potential ◽

Lc50 Value ◽

Vincristine Sulphate ◽

Dose Dependent

The present study was designed to investigate in vitro anthelmintic and cytotoxic activities of crude methanolic extract of two plants(Polygonum viscosum and Aphanamixis polystachya) grown in Bangladesh. Evaluation of cytotoxic activity was done using the brine shrimp lethality bioassay. The crude methanolic extract of Polygonum viscosum showed significant cytotoxic potential (LC50 value of 6.34 ?g/ml) among all the fractions comparing with that of standard vincristine sulphate (0.825 ?g/ml). Besides, the LC50 values of crude methanolic extract, pet ether and chloroform extracts of Aphanamixis polystachya showed good cytotoxic activities 11, 10.36, and 16.45 µg/ml, respectively. The other study was undertaken to evaluate anthelmintic activity (using Pheretima posthuma model) where piperazine was used as reference standard. The crude methanolic extract of Polygonum viscosum leaves produced a significant anthelmintic activity in dose dependent manner and the activity of crude extract was comparable with that of standard drugs. Besides, the Aphanamixis polystachya extract revealed moderate anthelmintic activity. Here, the anova testing was done with the P < 0.05. Further studies are suggested to determine the active compounds responsible for the anthelmintic and cytotoxic activities of these two plant extracts. Keywords: Anthelmintic; Cytotoxic; Medicinal plant; Aphanamixis polystachya; Polygonum viscosu. © 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v6i2.17299 J. Sci. Res. 6 (2), 339-345 (2014)

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Thrombolytic and Cytotoxic Activities of Terminalia bellerica Roxb.

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v16i2.22293 ◽

2015 ◽

Vol 16 (2) ◽

pp. 131-135

Author(s):

M Sekendar Ali ◽

Kazi Omar Faruq ◽

Atiqul Islam ◽

AMM Nurullah ◽

Kazi Ashfak Ahmed Chowdhury ◽

...

Keyword(s):

Brine Shrimp ◽

Thrombolytic Agent ◽

Methanolic Extract ◽

Pharmaceutical Journal ◽

Cytotoxic Activities ◽

Cytotoxic Potential ◽

Thrombolytic Activity ◽

Brine Shrimp Lethality ◽

Terminalia Bellerica ◽

Thrombolytic Effect

The present study was designed to investigate the thrombolytic activity and cytotoxic potential of the methanolic extract of bark of Terminalia bellerica Roxb. The cytotoxicity was assessed with the brine shrimp lethality bioassay and thrombolytic effect with human blood. The brine shrimp lethality bioassay was used to evaluate cytotoxicity (LC50 = 3.21 ?g/ml) compared to vincristine of sulphate (LC50 = 0.512 ?g /ml). It was also evaluated as thrombolytic agent as compared to streptokinase. It has significant thrombolytic activity (32.95%) compared to standard streptokinase (70%). DOI: http://dx.doi.org/10.3329/bpj.v16i2.22293 Bangladesh Pharmaceutical Journal 16(2): 131-135, 2013

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IMMUNOLOGIC PRODUCTION OF ANTIANGIOTENSIN

Journal of Experimental Medicine ◽

10.1084/jem.111.3.419 ◽

1960 ◽

Vol 111 (3) ◽

pp. 419-427 ◽

Cited By ~ 28

Author(s):

Sharad D. Deodhar

Keyword(s):

Biological Activity ◽

Angiotensin Ii ◽

Aromatic Amines ◽

Free Amino ◽

Parent Compound ◽

The Other ◽

Amino Group ◽

Angiotensin I ◽

Absolute Requirement ◽

Specific Activities

Angiotensin II was coupled with bovine γ-globulin (BGG) through the following series of reactions. See PDF for Structure By determinations of the aromatic amine and tyrosine contents of p-aminobenzoylangiotensin II, the number of p-aminobenzoyl residues introduced per molecule of angiotensin II was calculated. Absorption spectra (between 250 and 500 mµ) of BGG complexes of p-aminobenzoylangiotensin II and six different para substituted aromatic amines were compared. Specific activities (dog units/millimicromole) of the different intermediate products were determined. Presence of a terminal, free amino group does not appear to be an absolute requirement for the biological activity of angiotensin II, since substitution of a p-aminobenzoyl radical in this group yields a product with 40 to 50 per cent of the activity of the parent compound. Angiotensin I, on the other hand, is completely inactivated under identical circumstances. Possible implication of this finding has been discussed.

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