Celastrol As a Pentacyclic Triterpenoid With Chemopreventive Properties

Yadav, Priya; Jaswal, Vishal; Sharma, Ajay; Kashyap, Dharambir; Tuli, Hardeep Singh; Garg, Vivek Kumar; Das, Shonkor Kumar; Srinivas, R.

doi:10.4155/ppa-2017-0035

Cited by 37 publications

(24 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pentacyclic triterpenes are widely present in medicinal plants, and they show a unique range of pharmacological activities, including great antitumor, anti-inflammatory, and antiviral activities [ 4 , 5 , 6 ]. They attracted the attention of scholars due to their enormous chemopreventive and antineoplastic potential [ 7 , 8 ]. In view of this, the structural modification of pentacyclic triterpenoids is always a focus in drug research [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Fang

Zhang

Han

et al. 2018

IJMS

View full text Add to dashboard Cite

Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He–pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ± 0.59 μM), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was 3.85 ± 0.63 μM), while it showed lower cytotoxicity on H9c2 (murine heart myoblast; IC50 was 16.69 ± 0.12 μM) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure–activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.

show abstract

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Fang

Zhang

Han

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…The low cellular uptake of free Tri is perhaps related to its cytotoxicity that easily occurs cellular efflux. There is evidence indicating that Tri is a cytotoxic compound against a variety of cell lines (Yadav et al., 2018). When formulated into bilosomes, the cellular uptake of Tri was improved as revealed in the case of Tri-BLs.…”

Section: Resultsmentioning

confidence: 99%

Hyaluronic acid-functionalized bilosomes for targeted delivery of tripterine to inflamed area with enhancive therapy on arthritis

et al. 2019

View full text Add to dashboard Cite

Arthritis treatment has been challenging because of low drug exposure to the articular cavity. This study was intended to develop hyaluronic acid (HA)-functionalized bilosomes for targeted delivery of tripterine (Tri), an antiphlogistic phytomedicine, to the inflamed joint via ligand-receptor interaction. Tri-loaded bilosomes (Tri-BLs) with cationic lipid (DOTAP) were prepared by a thin film hydration method followed by HA coating to form HA@Tri-BLs. HA@Tri-BLs were then characterized by particle size (PS), entrapment efficiency (EE), and structural morphology. The in vitro drug release, hemocompatibility test and cellular uptake were performed to examine the formulation performances of HA@Tri-BLs. The in vivo pharmacokinetics and antiarthritic efficacy were evaluated in arthritic models, respectively. The obtained HA@Tri-BLs possessed a PS of 118.5 nm around with an EE of 99.56%. HA@Tri-BLs exhibited excellent cellular uptake and targeted delivery efficiency for Tri, which resulted in elongation of circulatory residence time and enhancement of intra-arthritic bioavailability (799.9% relative to Tri solution). The in vivo antiarthritic efficacy of HA@Tri-BLs was also significantly superior to uncoated Tri-BLs that gave rise to obvious inflammation resolution. Our findings suggest that HA-functionalized bilosomes are a promising vehicle for articular delivery of antiphlogistic drugs to potentiate their efficacy.

show abstract

“…A friedolanostane triterpenoid (methyl−3α,23−dihydroxy−17,14−friedolanstan−8,14,24−trien−26−oat) was isolated from Garcinia celebica L. and tested on MCF-7 breast cancer cell; the compound inhibited cell proliferation in a time- and dose-dependent manner by inhibiting the oncogenic protein AKT and increasing the expression of the poly (ADP-ribose) polymerase (PARP) protein thus promoting apoptosis and cell death ( 67 ). A natural friedo-oleanane triterpene, celastrol, found in the Celastraceae family, was the topic of a comprehensive review published in 2018 by Yadav et al who emphasized its activity on multiple proinflammatory, angiogenic and metastatic proteins thus inhibiting cancer growth, survival and metastasis; due to its large plethora of biological effects exerted through the modulation of a variety of intra- and extracellular signaling pathways, celastrol was the subject of numerous patents published between 2011 and 2017 and was embedded in modern complex nanoformulations ( 139 ).…”

Section: Triterpenes As Therapeutic Agents In Sex Hormone-dependent Cmentioning

confidence: 99%

Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

et al. 2021

View full text Add to dashboard Cite

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

show abstract

Celastrol As a Pentacyclic Triterpenoid With Chemopreventive Properties

Cited by 37 publications

References 71 publications

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin–Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis

Hyaluronic acid-functionalized bilosomes for targeted delivery of tripterine to inflamed area with enhancive therapy on arthritis

Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

Contact Info

Product

Resources

About