scholarly journals Evaluation of antimicrobial and anticancer activities of three peptides identified from the skin secretion of Hylarana latouchii

2021 ◽  
Author(s):  
Yan Lin ◽  
Tianxing Lin ◽  
Ningna Cheng ◽  
Shuting Wu ◽  
Jiancai Huang ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Human Cancer ◽  
Multidrug Resistant ◽  
Biologically Active ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Skin Secretion ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Close Relationship

Abstract The skins of frogs of the family Ranidae are particularly rich sources of biologically active peptides, among which antimicrobial peptides (AMPs) constitute the major portion. Some of these have attracted the interest of researchers because they possess both antimicrobial and anticancer activities. In this study, with ‘shotgun’ cloning and MS/MS fragmentation, three AMPs, homologues of family brevinin-1 (brevinin-1HL), and temporin (temporin-HLa and temporin-HLb), were discovered from the skin secretion of the broad-folded frog, Hylarana latouchii. They exhibited various degrees of antimicrobial and antibiofilm activities against test microorganisms and hemolysis on horse erythrocytes. It was found that they could induce bacteria death through disrupting cell membranes and binding to bacterial DNA. In addition, they also showed different potencies towards human cancer cell lines. The secondary structure and physicochemical properties of each peptide were investigated to preliminarily reveal their structure–activity relationships. Circular dichroism spectrometry showed that they all adopted a canonical α-helical conformation in membrane-mimetic solvents. Notably, the prepropeptide of brevinin-1HL from H. latouchii was highly identical to that of brevinin-1GHd from Hylarana guentheri, indicating a close relationship between these two species. Accordingly, this study provides candidates for the design of novel anti-infective and antineoplastic agents to fight multidrug-resistant bacteria and malignant tumors and also offers additional clues for the taxonomy of ranid frogs.

scholarly journals Bifunctional Phenol Quinone Methide Precursors: Synthesis and Biological Activity

2019 ◽  
Vol 92 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Matija Sambol ◽  
Katja Ester ◽  
Antonija Husak ◽  
Đani Škalamera ◽  
Ivo Piantanida ◽  
...  
Keyword(s):  
Biological Activity ◽  
Rational Design ◽  
Human Cancer ◽  
Conclusive Evidence ◽  
Biologically Active ◽  
Quinone Methide ◽  
Breast Adenocarcinoma ◽  
Cross Link ◽  
Human Cancer Cell Lines ◽  
Sequential Generation

New bifunctional quinone methide (QM) precursors, bisphenols 2a–2e, and monofunctional QM precursor 7 were synthesized. Upon treatment with fluoride, desilylation triggers formation of reactive intermediates, QMs, which was demonstrated by trapping QM with azide or methanol. The ability of QMs to alkylate and cross-link DNA was assayed by investigation of the effects of QMs to DNA denaturing, but without conclusive evidence. Furthermore, treatment of a plasmid DNA with compounds 2a–2e and KF, followed by the analysis by alkaline denaturing gel electrophoresis, did not provide evidence for the DNA cross-linking. MTT test performed on two human cancer cell lines (MCF7 breast adenocarcinoma and SUM159 pleomorphic breast carcinoma), with and without fluoride, indicated that 2a–2e or the corresponding QMs did not exhibit cytotoxic activity, in line with the lack of ability to cross-link DNA. The lack of reactivity with DNA and biological activity were explained by sequential formation of QMs where bifunctional cytotoxic reagent is probably never produced. Instead, the sequential generation of monofunctional QM followed by a faster hydrolysis leads to the destruction of biologically active reagent. The findings described here are particularly important for the rational design of new generation of QM precursor molecules that will attain desirable DNA reactivity and cytotoxicity.

scholarly journals Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 437
Author(s):  
Shu-Qin Qin ◽  
Lian-Chun Li ◽  
Jing-Ru Song ◽  
Hai-Yun Li ◽  
Dian-Peng Li
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

scholarly journals Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

2013 ◽  
Vol 57 (10) ◽  
pp. 4632-4639 ◽  
Author(s):  
Kairong Wang ◽  
Wen Dang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Social Wasp ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Content Type ◽  
Natural Analog ◽  
Action Mode

ABSTRACTWith the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social waspAgelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

scholarly journals Syntheses and Anticancer Activities of Novel Glucosylated (-)-Epigallocatechin-3-Gallate Derivatives Linked via Triazole Rings

2021 ◽  
Author(s):  
Cheng-Ting Zi ◽  
Bo-Ya Shi ◽  
Ze-Hao Wang ◽  
Ning Zhang ◽  
Yin-Rong Xie ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Anticancer Activities ◽  
Glucose Residue ◽  
Human Cancer Cell Lines ◽  
Mtt Assays ◽  
Mcf 7

Abstract Novel glucosylated (-)-epigallocatechin-3-gallate derivatives 10 – 13 having the EGCG analogues conjugated to the D-glucosyl azide were synthesized by carrying out the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and were evaluated for their cytotoxicities against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using MTT assays. Compounds 10 and 11 showed the highest levels of cytotoxicity against the HL-60 cells with IC50 values of 4.57 μM and 3.78 μM, respectively, and showed moderate selectivity towards cancer cell lines. Compound 11 was also shown to induce apoptosis in HL-60 cells. Most notably, inclusion of the perbutyrylated glucose residue in an EGCG derivative was concluded to lead to increased anticancer activity.

scholarly journals Brevinin-1GHd: a novel Hylarana guentheri skin secretion-derived Brevinin-1 type peptide with antimicrobial and anticancer therapeutic potential

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Yangyang Jiang ◽  
Yue Wu ◽  
Tao Wang ◽  
Xiaoling Chen ◽  
Mei Zhou ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Human Cancer ◽  
Wide Spectrum ◽  
Antimicrobial Properties ◽  
Skin Secretion ◽  
Anticancer Activities ◽  
Peptide Analog ◽  
Wide Range ◽  
Low Cytotoxicity ◽  
Short Time

Abstract Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the skin secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure–activity relationships also provided a rational template for further research and peptide analog design.

scholarly journals Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4860
Author(s):  
Ladislav Janovec ◽  
Eva Kovacova ◽  
Martina Semelakova ◽  
Monika Kvakova ◽  
Daniel Kupka ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Biologically Active ◽  
Standard Entropy ◽  
The Novel ◽  
Urea Derivatives ◽  
Human Cancer Cell Lines ◽  
Pharmacological Model

A novel series of proflavine ureas, derivatives 11a–11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b–0.44 μM, phenyl 11c–0.23 μM, phenylethyl 11f–0.35 μM and hexyl 11j–0.36 μM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.

scholarly journals Bauhinia variegataLeaf Extracts Exhibit Considerable Antibacterial, Antioxidant, and Anticancer Activities

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Amita Mishra ◽  
Amit Kumar Sharma ◽  
Shashank Kumar ◽  
Ajit K. Saxena ◽  
Abhay K. Pandey
Keyword(s):  
Cell Lines ◽  
Metal Ion ◽  
Human Cancer ◽  
Reducing Power ◽  
Ethanol Extract ◽  
Anticancer Activities ◽  
Leaf Extracts ◽  
Human Cancer Cell Lines ◽  
Polar Extracts ◽  
Mcf 7

The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities ofBauhinia variegataleaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11–222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition againstKlebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains ofE. coli,Proteusspp. andPseudomonasspp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract againstPseudomonasspp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10–40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction ofB. variegatashowed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90–99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities inB. variegataleaf extracts.

scholarly journals One-Pot Multicomponent Synthesis and Cytotoxic Evaluation of Novel 7-Substituted-5-(1H-Indol-3-yl)Tetrazolo[1,5-a] Pyrimidine-6-Carbonitrile

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 255
Author(s):  
Mohamed A. A. Radwan ◽  
Fahad M. Alminderej ◽  
Hanem M. Awad
Keyword(s):  
Human Cancer ◽  
Human Colon ◽  
Human Lung Cancer ◽  
Multicomponent Synthesis ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.

scholarly journals LFB: A Novel Antimicrobial Brevinin-Like Peptide from the Skin Secretion of the Fujian Large Headed Frog, Limnonectes fujianensi

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 242 ◽  
Author(s):  
Bin Li ◽  
Peng Lyu ◽  
Shuping Xie ◽  
Haixin Qin ◽  
Wenyuan Pu ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Human Cancer ◽  
Significant Activity ◽  
Negative Bacterium ◽  
Skin Secretion ◽  
Beta Turn ◽  
Gram Negative ◽  
Human Cancer Cell Lines ◽  
Ic50 Values

Amphibians are a natural source of abundant antimicrobial peptides and thus have been widely investigated for isolation of such biomolecules. Many new antimicrobial peptide families have been discovered from amphibians. In this study, a novel antimicrobial peptide named Limnonectes fujianensis Brevinvin (LFB) has been identified in the skin secretion from the Fujian large headed frog, Limnonectes fujianensis. The cDNA sequence was cloned from a skin secretion library and the predicted mature peptide was identified through MS/MS fragmentation sequencing of reverse phase HPLC fractions on the same sample. LFB was predicted to be an amphipathic, hydrophobic, alpha helical, and beta turn peptide that inserts into a lipid bilayer in order to kill the cells. In antimicrobial assays, a synthetic replicate of this novel antimicrobial peptide demonstrated significant activity against the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium Escherichia coli and the yeast, Candida albicans. This novel peptide was highly potent (MIC 4.88 uM) against Gram-negative bacterium, and also has the ability to inhibit the growth of human cancer cell lines with IC50 values ranging from 18.9 μM down to 2.0 μM. These findings help to enrich our understanding of Brevinin-like peptides. Moreover, the data presented here validate frog secretion as a source of potential novel antimicrobial peptides, that also exhibit anti-tumor properties, that could be useful for the treatment of cancer.

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