scholarly journals Pharmacological Characterisation of Pseudocerastes and Eristicophis Viper Venoms Reveal Anticancer (Melanoma) Properties and a Potentially Novel Mode of Fibrinogenolysis

2021 ◽  
Vol 22 (13) ◽  
pp. 6896
Author(s):  
Bianca op den Brouw ◽  
Parviz Ghezellou ◽  
Nicholas R. Casewell ◽  
Syed Abid Ali ◽  
Behzad Fathinia ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Serine Proteases ◽  
Human Melanoma ◽  
Snake Venoms ◽  
Lead Compounds ◽  
Bioactive Properties ◽  
Fibrinogenolytic Activity ◽  
Pharmacological Potential ◽  
Hydrolysis Of ◽  
Viper Venoms

Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the pharmacological potential of crude Pseudocerastes and Eristicophis snake venoms in haematological disorders and cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without protease inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine protease. We also found that the Pseudocerastes venoms significantly reduced the viability of human melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or anticancer agents.

scholarly journals Chloroquine Urea Derivatives: Synthesis and Antitumor Activity in Vitro

2018 ◽  
Vol 68 (4) ◽  
pp. 471-483 ◽  
Author(s):  
Kristina Pavić ◽  
Zrinka Rajić ◽  
Zvonimir Mlinarić ◽  
Lidija Uzelac ◽  
Marijeta Kralj ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Urea Derivatives ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Lead Compounds ◽  
Insight Into

Abstract In the current paper, we describe the design, synthesis and antiproliferative screening of novel chloroquine derivatives with a quinoline core linked to a hydroxy or halogen amine through a flexible aminobutyl chain and urea spacer. Synthetic pathway leading to chloroquine urea derivatives 4-10 includes two crucial steps: i) synthesis of chloroquine benzotriazolide 3 and ii) formation of urea derivatives through the reaction of compound 3 with the corresponding amine. Testing of antiproliferative activity against four human cancer cell lines revealed that chloroquine urea derivatives 9 and 10 with aromatic moieties show activity at micromolar concentrations. Therefore, these molecules represent interesting lead compounds that might provide an insight into the design of new anticancer agents.

scholarly journals Baccharis dracunculifolia and Dalbergia ecastophyllum, Main Plant Sources for Bioactive Properties in Green and Red Brazilian Propolis

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1619
Author(s):  
Adela Ramona Moise ◽  
Otilia Bobiş
Keyword(s):  
Chemical Composition ◽  
Antioxidant Activities ◽  
Pharmaceutical Products ◽  
Raw Material ◽  
Bioactive Properties ◽  
Different Types ◽  
Scientific Papers ◽  
Valuable Product ◽  
Brazilian Propolis ◽  
Pharmacological Potential

Nowadays, propolis is used as a highly valuable product in alternative medicine for improving health or treating a large spectrum of pathologies, an ingredient in pharmaceutical products, and also as a food additive. Different vegetal materials are collected by honeybees and mixed with wax and other own substances in order to obtain the final product, called propolis. It is known as the bee product with the widest chemical composition due to the raw material collected by the bees. Different types are known worldwide: green Brazilian propolis (having Baccharis dracunculifolia as the major plant source), red Brazilian propolis (from Dalbergia ecastophyllum), European propolis (Populus nigra L.), Russian propolis (Betula verrucosa Ehrh), Cuban and Venezuelan red propolis (Clusia spp.), etc. An impressive number of scientific papers already demonstrate the pharmacological potential of different types of propolis, the most important activities being the antimicrobial, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. However, the bioactive compounds responsible for each activity have not been fully elucidated. This review aims to collect important data about the chemical composition and bioactive properties of the vegetal sources and to compare with the chemical composition of respective propolis types, in order to determine the connection between the floral source and the propolis properties.

scholarly journals Design and Evaluation of Licochalcone A Derivatives as Anticancer Agents

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300
Author(s):  
Goo Yoon ◽  
Seung Hoon Cheon ◽  
Jung Hyun Shim ◽  
Seung Sik Cho
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Licochalcone A ◽  
Lead Compounds ◽  
Further Development ◽  
Derivatives Of

New derivatives of licochalcone A were synthesized and evaluated for their potential anticancer activities. Compounds 6 (( E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxy phenyl) acryloyl) phenyl)-4-isopropylbenzamide) and 8 (1-(3-dimethylamino-phenyl)-3-(2-trifluoromethyl-phenyl)-propenone) showed potent activity against the screened cancer cell lines with that of compound 6 ranging from 6.9 ± 0.2 μM to 22.9 ± 3.1 μM, and that of compound 8 from 4.2 ± 0.5 μM to 11.8 ± 0.7 μM. Both compounds showed stronger cytotoxicity than that of licochalcone A. These two candidates have very different substituents and could be considered as promising lead compounds for further development of potent anticancer agents.

scholarly journals Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

2019 ◽  
Vol 12 (4) ◽  
pp. 146 ◽  
Author(s):  
Claudia Riccardi ◽  
Domenica Musumeci ◽  
Marco Trifuoggi ◽  
Carlo Irace ◽  
Luigi Paduano ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Biomedical Applications ◽  
Special Focus ◽  
Anticancer Properties ◽  
Pharmacokinetic Properties ◽  
Pharmacological Potential

The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications.

scholarly journals Molecular insight into isoform specific inhibition of PI3K-α and PKC-η with dietary agents through an ensemble pharmacophore and docking studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Baki Vijaya Bhaskar ◽  
Aluru Rammohan ◽  
Tirumalasetty Munichandra Babu ◽  
Gui Yu Zheng ◽  
Weibin Chen ◽  
...  
Keyword(s):  
Binding Energy ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Binding Pocket ◽  
Pharmacophore Modeling ◽  
Boswellic Acid ◽  
Lead Compounds ◽  
Donor And Acceptor ◽  
In Silico Studies ◽  
Dietary Agents

AbstractDietary compounds play an important role in the prevention and treatment of many cancers, although their specific molecular mechanism is not yet known. In the present study, thirty dietary agents were analyzed on nine drug targets through in silico studies. However, nine dietary scaffolds, such as silibinin, flavopiridol, oleandrin, ursolic acid, α-boswellic acid, β-boswellic acid, triterpenoid, guggulsterone, and oleanolic acid potentially bound to the cavity of PI3K-α, PKC-η, H-Ras, and Ras with the highest binding energy. Particularly, the compounds silibinin and flavopiridol have been shown to have broad spectrum anticancer activity. Interestingly, flavopiridol was embedded in the pockets of PI3K-α and PKC-η as bound crystal inhibitors in two different conformations and showed significant interactions with ATP binding pocket residues. However, complex-based pharmacophore modeling achieved two vital pharmacophoric features namely, two H-bond acceptors for PI3K-α, while three are hydrophobic, one cat-donor and one H-bond donor and acceptor for PKC-η, respectively. The database screening with the ChemBridge core library explored potential hits on a valid pharmacophore query. Therefore, to optimize perspective lead compounds from the hits, which were subjected to various constraints such as docking, MM/GBVI, Lipinski rule of five, ADMET and toxicity properties. Henceforth, the top ligands were sorted out and examined for vital interactions with key residues, arguably the top three promising lead compounds for PI3K-α, while seven for PKC-η, exhibiting binding energy from − 11.5 to − 8.5 kcal mol−1. Therefore, these scaffolds could be helpful in the development of novel class of effective anticancer agents.

scholarly journals Synthesis, Molecular Docking and Anticancer Activity of Novel 1,3-Thiazolidin-4-Ones

2020 ◽  
Vol 27 (3) ◽  
pp. 345-352
Author(s):  
Ramesh Sawant ◽  
Jyoti Wadekar ◽  
Rushikesh Ukirde ◽  
Ganesh Barkade
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Lead Compounds ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Further Development ◽  
Mcf 7 ◽  
Clinical Strategy

Background: Cancer is a major cause of death all over the globe. Controlling cell division byinhibition of mitosis is the most successful clinical strategy for cancer treatment. The developmentof novel anticancer agents is the most important area in medicinal chemistry and drug discoveryresearch. Thiazolidine is the multifunctional nucleus which shows a number of pharmacologicalactivities like anticancer, anti-inflammatory, antioxidant, antibacterial, antifungal, antidiabetic,antihyperlipidemic and antiarthritic. Methods: In a present study series of 2-substituted-3-(1H-benzimidazole-2-yl)-thiazolidin-4-ones were designed, synthesized by the microwave-assisted system, and characterized bymelting point, IR, 1H NMR, and mass spectroscopy. All the newly synthesized compoundswere examined for their in vitro anticancer activity against breast cancer cell line MCF-7 bySulforhodamine B (SRB) assay. Results: The compounds AB-12 (GI50: 28.5 μg/ml) and AB-6 (GI50: 50.7 μg/ml) exhibitedsignificant cell growth inhibitory activity. Conclusion: These results indicate that compound AB-12 and AB-6 as related polo-like kinase1inhibitors compounds could be lead compounds for further development of anticanceragents.

scholarly journals A Genus-Wide Bioactivity Analysis of Daboia (Viperinae: Viperidae) Viper Venoms Reveals Widespread Variation in Haemotoxic Properties

2021 ◽  
Vol 22 (24) ◽  
pp. 13486
Author(s):  
Bianca op den Brouw ◽  
Francisco C. P. Coimbra ◽  
Nicholas R. Casewell ◽  
Syed Abid Ali ◽  
Freek J. Vonk ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Human Plasma ◽  
Dose Response ◽  
Factor X ◽  
African Species ◽  
Human Fibrinogen ◽  
Fibrinogenolytic Activity ◽  
The Many ◽  
Viper Venoms ◽  
Multiple Variants

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.

Recent Advances of Novel Therapeutic Agents from Botanicals for Prevention and Therapy of Breast Cancer: An Updated Review

2020 ◽  
Vol 16 (1) ◽  
pp. 5-18
Author(s):  
Namrata Singh ◽  
Poonam Kushwaha ◽  
Amresh Gupta ◽  
Om Prakash
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Anticancer Agents ◽  
Alternative Therapy ◽  
Complementary And Alternative Therapy ◽  
Lead Compounds ◽  
Biomedical Innovation ◽  
Bioactive Agents ◽  
Day By Day ◽  
Preventive Role

Breast cancer is among the foremost common malignancies and the second leading cause for cancer-related deaths in females. Varied treatment approaches are projected to cause a subject matter reduction in the fatality rate. Carcinoma treatment is highly challenging due to therapeutic resistance and reoccurrence. Several studies have revealed that bioactive compounds isolated from natural products such as plants, vegetables, and marine origins have a therapeutic and preventive role in breast carcinoma. Utilization of these bioactive agents in amelioration of cancer as complementary and alternative therapy increases day by day due to growing scientific shreds of evidence of the biomedical innovation and clinical trials. Due to the safe nature of these photochemical investigators are focusing on the investigation of lead compounds from traditional herbal medicine to discover new lead anticancer agents in the single pure compound. This review highlights the mechanism of action and future prospects of novel medicinal agents from botanical sources that have chemoprevention activity against breast carcinoma together with other types of body cancer. The major bioactive, which are used as a remedy for the prevention and treatment of breast cancer, is summarized and explored here.

Sign in / Sign up

Export Citation Format

Share Document