scholarly journals Synthesis, and Docking Studies of Novel Heterocycles Incorporating the Indazolylthiazole Moiety as Antimicrobial and Anticancer Agents

2021 ◽  
Author(s):  
Nadia Dawoud ◽  
Hamada El-Gendi ◽  
Abdallah Abdallah ◽  
Esmail M. El-Fakharany ◽  
Doaa Lotfy
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Antitumor Activity ◽  
Streptococcus Mutans ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Maximum Activity ◽  
Dependent Manner ◽  
Molecular Docking Study

Abstract The current study was directed toward developing a new series of fused heterocycles incorporating an indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and mass spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with a lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about approximately 26 and an IC50 value of approximately 5.9 µg/ml. The effect of these derivatives (8, 4, and 6) on the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where their interaction with these genes was simulated through a molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have potential antimicrobial activity, with maximum broad spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed antibiofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans.

Complexes of Cu (II) with a-Ketoglutaric Acid and 1- (o-tolyl) Biguanide Synthesis, characterization and biological Activity

2019 ◽  
Vol 70 (10) ◽  
pp. 3603-3610
Author(s):  
Madalina Mihalache ◽  
Cornelia Guran ◽  
Aurelia Meghea ◽  
Vasile Bercu ◽  
Ludmila Motelica ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Biological Activity ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Copper Complexes ◽  
Substrate Adhesion ◽  
Inert Substrate

The three copper complexes having a-ketoglutaric acid (H2A) and 1- (o-tolyl) biguanide (TB) ligands have been synthesized and characterized. The proposed formulas for these complexes are: [Cu(TB)(HA)]Cl (C1), [Cu(TB)(HA)CH3COO]�H2O (C2) and [Cu(TB)(HA)](NO3) (C3) where HA represents deprotonated H2A. The complexes obtained were tested for antibacterial activity against Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853, antifungal activity on Candida albicans ATCC 10231 and antitumor activity on HeLa tumor cells. Due to the antitumor, antifungal, antimicrobial activity and inhibition of inert substrate adhesion, complexes synthesized could be used for potential therapeutic applications.

scholarly journals Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 745
Author(s):  
Melaine González-García ◽  
Fidel Morales-Vicente ◽  
Erbio Díaz Pico ◽  
Hilda Garay ◽  
Daniel G. Rivera ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Multidrug Resistant ◽  
Moderate Activity ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Acinetobacter Baumanii ◽  
Concentration Dependent Manner ◽  
Conventional Antibiotics

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.

scholarly journals Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 630
Author(s):  
Hawon Yoo ◽  
Seul-Ki Choi ◽  
Jaeok Lee ◽  
So Hyeon Park ◽  
You Na Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Hsp27 Expression ◽  
Cancer Aggressiveness

Relationships between heat shock protein 27 (HSP27) and cancer aggressiveness, metastasis, drug resistance, and poor patient outcomes in various cancer types including non-small cell lung cancer (NSCLC) were reported, and inhibition of HSP27 expression is suggested to be a possible strategy for cancer therapy. Unlike HSP90 or HSP70, HSP27 does not have an ATP-binding pocket, and no effective HSP27 inhibitors have been identified. Previously, NSCLC cancer cells were sensitized to radiation and chemotherapy when co-treated with small molecule HSP27 functional inhibitors such as zerumbone (ZER), SW15, and J2 that can induce abnormal cross-linked HSP27 dimer. In this study, cancer inhibition effects of NA49, a chromenone compound with better solubility, longer circulation time, and less toxicity than J2, were examined in combination with anticancer drugs such as cisplatin and gefitinib in NSCLC cell lines. When the cytotoxic drug cisplatin was treated in combination with NA49 in epidermal growth factor receptors (EGFRs) WT cell lines, sensitization was induced in an HSP27 expression-dependent manner. With gefitinib treatment, NA49 showed increased combination effects in both EGFR WT and Mut cell lines, also with HSP27 expression-dependent patterns. Moreover, NA49 induced sensitization in EGFR Mut cells with a secondary mutation of T790M when combined with gefitinib. Augmented tumor growth inhibition was shown with the combination of cisplatin or gefitinib and NA49 in nude mouse xenograft models. These results suggest the combination of HSP27 inhibitor NA49 and anticancer agents as a candidate for overcoming HSP27-mediated drug resistance in NSCLC patients.

scholarly journals Evaluation of pro-apoptotic potential of taxifolin against liver cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11276
Author(s):  
Sania Safdar Butt ◽  
Khushbukhat Khan ◽  
Yasmin Badshah ◽  
Mehak Rafiq ◽  
Maria Shabbir
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Therapeutic Potential ◽  
Huh7 Cell ◽  
Dependent Manner ◽  
Dna Ladder ◽  
Cell Viability Assay ◽  
Migration Assay ◽  
In Silico Docking

Liver cancer is the second most common cause of cancer-induced deaths worldwide. Liver cirrhosis and cancer are a consequence of the abnormal angio-architecture formation of liver and formation of new blood vessels. This angiogenesis is driven by overexpression of hypoxia-inducible factor 1-alpha (Hif1-α) and vascular endothelial growth factor (VEGF). Apart from this, protein kinase B (Akt) is also impaired in liver cancer. Despite the advancement in conventional treatments, liver cancer remains largely incurable. Nowadays, the use of naturally occurring anticancer agents particularly flavonoids is subject to more attention due to their enhanced physicochemical properties. Therefore, this study underlines the use of a natural anticancer agent taxifolin in the treatment of liver cancer using hepatocellular carcinoma cell line HepG2 and Huh7. The aim of our study is to devise a natural and efficient solution for the disease prevalent in Pakistan. The study involved the assessment of binding of ligand taxifolin using molecular docking. The binding of taxifolin with the proteins (Hif1-α, VEGF and Akt) was calculated by docking using Vina and Chimera. Further evaluation was performed by cell viability assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay), colony formation assay, cell migration assay, DNA ladder assay and flow cytometry. To see whether taxifolin directly affected expression levels, analysis of gene expression of Hif1-α, VEGF and Akt was performed using real-time polymerase chain reaction (qPCR) and western blotting. In silico docking experiments revealed that these proteins showed favorable docking scores with taxifolin. Treatment with taxifolin resulted in the inhibition of the liver cancer growth and migration, and induced apoptosis in HepG2 and Huh7 cell lines at an inhibitory concentration (IC50) value of 0.15 µM and 0.22 µM, respectively. The expression of HIF1-α, VEGF and Akt was significantly reduced in a dose- dependent manner. The inhibitory effect of taxifolin on hepatic cells suggested its chemopreventive and therapeutic potential. The studied compound taxifolin exhibited pronounced pro-apoptotic and hepatoprotective potential. Our study has confirmed the pro-apoptotic potential of taxifolin in liver cancer cell lines and will pave a way to the use of taxifolin as a chemotherapeutic agent after its further validation on the animal models and humans based epidemiological studies.

scholarly journals In vitroAnticancer Evaluation of Saponins Obtained From Spirulina platensis on MDA, HepG2, and MCF7 Cell Lines

2019 ◽  
Vol 3 (4) ◽  
pp. 25-32
Author(s):  
Mahboobeh Akbarizare ◽  
Hamideh Ofoghi ◽  
Mahnaz Hadizadeh
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Spirulina Platensis ◽  
Dependent Manner ◽  
Cellular Viability ◽  
Breast Cancers ◽  
Anticancer Activities ◽  
Concentration Dependent Manner ◽  
Photosynthetic Microorganism ◽  
Mcf 7

Introduction: Microalgae are known for their bioactive compounds with potential applications as antimicrobial, antiaging, and anticancer activities. Spirulina platensis (S. platensis) is a filamentous and photosynthetic microorganism that has 25 kinds of vitamins and minerals that contain many compounds with biotic activity such as alkaloids, phenolic compounds, terpenoids, and saponins. Saponins are mainly present in plants; while there are few studies about their role in microalgae. This study aims to investigate the anticancer potential of extracted saponins from S. platensis. Methods: Saponins were extracted; using distilled water and n-butanol. The total extracted saponin was dried and weighed. The cellular viability of HepG2, MCF-7, and MDA- MB-123 cell lines was evaluated; using MTT assay after 24 h treatment with 0.02-2 mg/ ml of saponins extracted from S. platensis. Morphology of cell lines was evaluated by invert microscopy. Results: Total saponin extracted from S. platensis was estimated at 28±0.0005 mg/g dry wt. Thin-layer chromatography profiles showed four bands for saponins with Rf values of 0.44, 0.48, 0.50, and 0.55. The cytotoxic activity after 24 h treatment with 0.02-2 mg/ml of saponins was a concentration-dependent manner. The highest toxicity of saponins with IC50=0.22 mg/ml was observed in MDA-MB-123 cells. In HepG2 and MCF-7 cells IC50 value was obtained in 0.35 mg/ml and 0.4 mg/ml, respectively. Conclusions: This is the first report to evaluate the anticancer effects of saponins from S. platensis in liver and breast cancers. The result showed that saponins from Spirulina decrease cancer cellular viability. Therefore, these compounds can be a candidate for anticancer agents.

scholarly journals VARIATIONS IN ANTIMICROBIAL ACTIVITY OF SYZYGIUM CUMINI OF DIFFERENT GEOGRAPHICAL LOCATIONS

2020 ◽  
pp. 1-6
Author(s):  
Pratibha ◽  
Nesari Tanuja ◽  
Ghildiyal Shivani ◽  
Vandhana
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Streptococcus Pyogenes ◽  
Antimicrobial Agents ◽  
Diffusion Method ◽  
Klebsiella Pneumonia ◽  
Syzygium Cumini ◽  
Geographical Variations ◽  
Geographical Locations

The emergence of antibiotic resistance and the evolution of new strains of disease causing agents, are of highly concern to the global health community. Plants are potential source of antimicrobial agents. They have been used traditionally for prevention of infections caused by micro-organisms. Description of Krimighana herbs enumerated in Ayurveda classics is suggestive towards the importance of this group of medicine. Jambu (Syzygium cumini (L.) Skeels) is a member of Myrtaceae family. In Raja Nighantu it is mentioned that plant Jambu is having Kriminashaka property. It has been widely used medicine in the prevention of various ailments like cough, Dysentary, Diabetes, inflammation and ringworm. It is well established fact that geographical variations effects the potential and activity of medicinal herbs. Hence, the present study was undertaken to investigate Syzygium cumini procured from different geographical locations including Delhi, Rajasthan and Maharashtra for their potential activity against human infections caused by pathogens. Method The aqueous extract of Syzygium cumini of all the three areas was prepared. The activity of the plant extract was evaluated against nine bacterial pathogens and one fungal strain, which include Staphyllococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Klebsiella pneumonia and Candida albicans. The activity was carried out using Disk diffusion method. Result and Conclusion: All samples of Syzygium cumini showed potential antimicrobial activity against four pathogens including Staphyllococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Candida albicans. MIC was also evaluated against the tested pathogenic strains. The sample from Maharashtra showed MIC i.e. 80µg, 40µg, 80µg against Staphyllococcus aureus, Streptococcus pyogenes and Candida albicans respectively which is less as compare to sample from Rajasthan and Delhi. Region wise sample from Maharashtra showed good ZOI and MIC.

Design, Synthesis, Molecular Docking and Biological Studies of New Heterocyclic Compounds Derived from -Diketonesas Novel EGFR and Pim-1 Inhibitors Endowed with Antitumor Activity

2022 ◽  
Vol 22 ◽  
Author(s):  
Rafat Milad Mohareb ◽  
Noha M. Asaad Bagato ◽  
Ibrahim Taha Radwan
Keyword(s):  
Molecular Docking ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Diethyl Malonate ◽  
Binding Mode ◽  
Binding Modes ◽  
Binding Interactions ◽  
Biological Studies

Background: Cancer is a disease illustrated by a shift in the controlled mechanisms that control both cell proliferation and differentiation. It is regarded as a prime health problem worldwide, leading cause of human death-rate exceeded only by cardiovascular diseases. Many reported work was concerned with the discovery of new antitumor compounds this encourage us to synthesis new anticancer agents. Objective: In this work, we are aiming to synthesize target molecules from 1,3-dicarbonyl compounds through many heterocyclization reactions. Method: The reaction of either 4-methylaniline (1a) or 1-naphthylamine (1b) with diethyl malonate (2) gave the anilide derivatives 3a and 3b, respectively. The latter products underwent a series of heterocyclization reactions to give the pyridine, pyran andthiazole derivatives which confirmed with the required spectral data. Results: Thein-vitro antitumor evaluations of the newly synthesized products against four cancer cell lines MCF-7, NCI-H460, SF-268 and WI 38 as normal cell line were screened and the data revealed that compounds 11a, 18b, 18c and 20d showed high antitumor activity and 20dindividualize with potential antitumor activity towards cell lines with lowest cytotoxicity effect. Both EGFR and PIM-1 enzyme inhibition were investigated for the compound 20d and his inhibition effect was promising for each enzyme showing IC50=45.67 ng and 553.3 ng for EGFR and PIM-1, respectively. Conclusion: Molecular docking results of compound 20d showed a strong binding interactions on both enzymes, where, good binding modes obtained on case of EGFR, which closely similar to the binding mode of standard Erlotinib. While, 20d showed complete superimposition binding interactions with VRV-cocrystallized ligand of PIM-1 that may expounds the in-vitro antitumor activity.

Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

2021 ◽  
Vol 13 (20) ◽  
pp. 1743-1766
Author(s):  
Islam H El Azab ◽  
Essa M Saied ◽  
Alaa A Osman ◽  
Amir E Mehana ◽  
Hosam A Saad ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
In Silico ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Molecular Docking Study ◽  
In Silico Studies

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.

Sign in / Sign up

Export Citation Format

Share Document