Bioactivity guided isolation of oxypregnane-oligoglycosides (calotroposides) from the root bark of Calotropis gigantea as potent anticancer agents

RSC Advances ◽  
2016 ◽  
Vol 6 (106) ◽  
pp. 104215-104226 ◽  
Author(s):  
Rohit Mahar ◽  
Shivani Dixit ◽  
Trapti Joshi ◽  
Sanjeev Kanojiya ◽  
Dipak K. Mishra ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Ethanolic Extract ◽  
Root Bark ◽  
Calotropis Gigantea ◽  
Pure Compounds

Bioactivity guided isolation of oxypregnane-oligoglycosides (calotroposides) from the ethanolic extract of root bark of Calotropis gigantea (L.) Dryand. with purple flowers has been performed and isolated pure compounds has been evaluated for anticancer activity.

Calotropis gigantea- A Review

2021 ◽  
pp. 261-264
Author(s):  
Snehal Lad ◽  
Priya S. Rao ◽  
Dattaprasad N Vikhe
Keyword(s):  
Methanolic Extract ◽  
Chemical Constituents ◽  
Ethanolic Extract ◽  
The Body ◽  
Perennial Herb ◽  
Root Bark ◽  
Nootropic Activity ◽  
Calotropis Gigantea ◽  
Traditional Medicines ◽  
History Of Use

Calotropis gigantea plant has a family Asclepiadaceae commonly and sub family Apocynaceae known as Madar in Hindi. It is a perennial herb with a very long history of use in traditional medicines. Calotropis gigantea is a hoary, laticiferous shrub, which is also known as “the milkweed”. Calotropis is used as a traditional medicinal plant in whole world. Calotropis gigantea plant contain chemical constituents in which cardenolides, flavonoids, terpenes, pregnanes and nonprotein amino acid and more in various concentration. The root bark contains α-amyrin, β-amyrin, taraxasterol and its ψ-isomer taraxasteryl isovalerate, taraxasteryl acetate, gigantin, giganteol, isogiganteol, β-sitosterol and wax. The rootalso shows Nootropic activity in methanolic extract. The latex, leaves, flowers and bark are used as caustic, acrid, expectorant, to removes body hairs, anthelmintics and alsoused in leprosy, ulceration, cough, scabies ring worm of the scalp, piles, explosion on the body, asthma, enlargement of spleen or liver, edema and in painful joint swellings. Also, evaluate possible anxiogenic effect, sedative action and anxiolytic potential of crude ethanolic extract of Calotropis gigantealeaf. Methanolic extract of Calotropis gigantea root used as memory increasing activity. This review gives an idea about its pharmacological activity and phytochemistry.

Hepatoprotective Activity of Calotropis gigantea Root Bark Experimental Liver Damage Induced by D-Galactosamine in Rats

1970 ◽  
Vol 1 (3) ◽  
pp. 281-286
Author(s):  
Pradeep Deshmukh ◽  
Tanaji Nandgude ◽  
Mahendra Singh Rathode ◽  
Anil Midha ◽  
Nitin Jaiswal
Keyword(s):  
Methyl Cellulose ◽  
Hepatoprotective Activity ◽  
Albino Rats ◽  
Root Bark ◽  
Significant Activity ◽  
Alcoholic Extract ◽  
Calotropis Gigantea ◽  
Wistar Albino Rats ◽  
Experimental Liver ◽  
Hepatoprotective Drug

The suspensions of alcoholic extract of root bark of the plant Calotropis gigantea in 0.6% carboxy methyl cellulose (CMC) were evaluated for hepatoprotective activity in Wistar albino rats by inducing hepatic injury with D-galactosamine (400 mg/kg). Alcoholic extract of root bark of the plant Calotropis gigantea at an oral dose of 200 mg/kg and 400 mg/kg exhibited a significant (P<0.001, P<0.01 and P<0.05) protection effect by normalizing the levels of aspartate amino transferase (ASAT/ GOT), alanine amino transferase (ALAT/GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), which were significantly (P<0.001) increased in rats by treatment with 400 mg/kg i.p. of D-galactosamine. Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001).

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

Synthesis, Characterization, Anti-proliferative Evaluation, and DNA Flow Cytometry Analysis of Some 2-Thiohydantoin Derivatives

2020 ◽  
Vol 20 (18) ◽  
pp. 1929-1941
Author(s):  
Heba A. Elhady ◽  
Hossa F. Al-Shareef
Keyword(s):  
Anticancer Activity ◽  
Schiff Bases ◽  
Anticancer Agents ◽  
Proliferative Activity ◽  
Cancer Cell Line ◽  
Aromatic Aldehydes ◽  
Pharmaceutical Chemistry ◽  
Dna Flow Cytometry ◽  
Quinazoline Derivative ◽  
Reference Drug

Background and Objective: Due to the well-documented anti-proliferative activity of 2-thiohydantoin incorporated with pyrazole, oxadiazole, quinazoline, urea, β-naphthyl carbamate and Schiff bases, they are noteworthy in pharmaceutical chemistry. Methods: An efficient approach for the synthesis of a novel series of 2-thiohydantoin derivatives incorporated with pyrazole and oxadiazole has proceeded via the reaction of the acyl hydrazide with chalcones and/or triethyl orthoformate. Schiff bases were synthesized by the reaction of the acyl hydrazide with different aromatic aldehydes. Moreover, Curtius rearrangement was applied to the acyl azide to obtain the urea derivative, quinazoline derivative, and carbamate derivative. Results: The synthesized compounds structures were discussed and confirmed depending on their spectral data. The anticancer activity of these heterocyclic compounds was evaluated against the breast cancer cell line (MCF-7), where they showed variable activity. Compound 5d found to have a superior anticancer activity, where it has (IC50 = 2.07 ± 0.13 μg/mL) in comparison with the reference drug doxorubicin that has (IC50 = 2.79 ± 0.07 μg / mL). Then compound 5d subjected to further studies such as cell cycle analysis and apoptosis. Apoptosis was confirmed by the upregulation of Bax, downregulation of Bcl-2, and the increase of the caspase 3/7percentage. Conclusion: Insertion of pyrazole, oxadiazole and, quinazoline moieties with 2-thiohydantoin moiety led to the enhancement of its anti-proliferative activity. Hence they can be used as anticancer agents.

Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

2020 ◽  
Vol 17 (10) ◽  
pp. 772-778
Author(s):  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Yahya I. Asiri ◽  
Jaber Abdullah Alshehri ◽  
Yahia N. Mabkhot ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Mode ◽  
Docking Studies ◽  
Solvent Free ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Solvent Free Conditions ◽  
Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cdk Inhibitors ◽  
Comprehensive Overview ◽  
P53 Expression ◽  
Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

scholarly journals Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1790
Author(s):  
Katarzyna Malarz ◽  
Jacek Mularski ◽  
Michał Kuczak ◽  
Anna Mrozek-Wilczkiewicz ◽  
Robert Musiol
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
P53 Protein ◽  
Structural Similarity ◽  
M Cell ◽  
Cycle Arrest ◽  
Small Series

Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as convenient intermediates in a synthesis. Here, we present the first in-depth investigation of quinazoline sulfonates. A small series of derivatives were synthesized and tested for their anticancer activity. Based on their structural similarity, these compounds resemble tyrosine kinase inhibitors and the p53 reactivator CP-31398. Their biological activity profile, however, was more related to sulphonamides because there was a strong cell cycle arrest in the G2/M phase. Further investigation revealed a multitargeted mechanism of the action that corresponded to the p53 protein status in the cell. Although the compounds expressed a high submicromolar activity against leukemia and colon cancers, pancreatic cancer and glioblastoma were also susceptible. Apoptosis and autophagy were confirmed as the cell death modes that corresponded with the inhibition of metabolic activity and the activation of the p53-dependent and p53-independent pathways. Namely, there was a strong activation of the p62 protein and GADD44. Other proteins such as cdc2 were also expressed at a higher level. Moreover, the classical caspase-dependent pathway in leukemia was observed at a lower concentration, which again confirmed a multitargeted mechanism. It can therefore be concluded that the sulfonates of quinazolines can be regarded as promising scaffolds for developing anticancer agents.

scholarly journals CLVII.—The root bark of Calotropis gigantea

1915 ◽  
Vol 107 (0) ◽  
pp. 1437-1442 ◽  
Author(s):  
Ernest George Hill ◽  
Annoda Prasad Sirkar
Keyword(s):  
Root Bark ◽  
Calotropis Gigantea

scholarly journals NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Anticancer Activities ◽  
Gene Expressions

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.

Sign in / Sign up

Export Citation Format

Share Document