Chemistry, Bioactivity, and the Structure-Activity Relationship of Cephalotaxine-Type Alkaloids From Cephalotaxus sp.

Chang, Yu Wei; Meng, Fan-Cheng; Wang, Ruoyan; Wang, C.M.; Lu, Xiao; Zhang, Q.-W.

doi:10.1016/b978-0-444-63930-1.00010-7

Cited by 23 publications

(19 citation statements)

References 88 publications

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“…The interest in homoharringtonine started when its potent antiproliferative activity against murine P-388 leukemia cells with IC 50 values of 17 nM was demonstrated [ 69 ]. In fact, since the 1970s homoharringtonine or a mixture of cephalotaxine esters has been used in China to treat hematological malignancies [ 70 ].…”

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

“…The identification of several natural cephalotaxine esters structurally similar to homoharringtonine and other derivatives obtained by semisynthesis allowed establishing some structure activity relationships, which were recently reviewed and discussed by Chang et al [ 69 ]. The most important SAR are: (i) the cephalotaxine nucleus is much less active against the P388 cell line than its esters derivatives; (ii) an aliphatic side chain bonded to the hydroxyl group at C-3 seems to be necessary to enhance the activity; (iii) the presence of hydroxyl groups at C-11 or C-3′ decreases the activity; (iv) a free carboxylic acid at C-4′ abruptly decreases the activity; however, the methyl group can be replaced by other alkyl groups, even bulky ones, without the loss of the activity and in some cases enhancing it; (v) bulky groups bonded to 8′-OH are also tolerated; (vi) substituents bonded at 2′-OH imply a significant loss of activity ( Figure 4 ).…”

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

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Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Seca

Pinto

2018

IJMS

494

293

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Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each compound’s natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.

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Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Seca

Pinto

2018

IJMS

494

293

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“…From a medicinal chemistry point of view, a tremendous amount of plant extraction analysis and synthetic work has been done during the past 40 years concerning cephalotaxine esters and HHT derivatives: almost 60 molecules have been extracted from natural sources, tested, and their structures resolved [87]. In their patent, Bataille et al have exemplified and tested about 65 analogues [88].…”

Section: Homoharringtonine a Clinically Used Ribosome Inhibitormentioning

confidence: 99%

Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies

Gilles

Fréchin

Natchiar

et al. 2020

Cells

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The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic proteins and provides cancerous proliferating cells with proteins and therefore biomass. Indeed, cancer is associated with an increase in ribosome biogenesis and mutations in several ribosomal proteins genes are found in ribosomopathies, which are congenital diseases that display an elevated risk of cancer. Ribosomes and their biogenesis therefore represent attractive anti-cancer targets and several strategies are being developed to identify efficient and specific drugs. Homoharringtonine (HHT) is the only direct ribosome inhibitor currently used in clinics for cancer treatments, although many classical chemotherapeutic drugs also appear to impact on protein synthesis. Here we review the role of the human ribosome as a medical target in cancer, and how functional and structural analysis combined with chemical synthesis of new inhibitors can synergize. The possible existence of oncoribosomes is also discussed. The emerging idea is that targeting the human ribosome could not only allow the interference with cancer cell addiction towards protein synthesis and possibly induce their death but may also be highly valuable to decrease the levels of oncogenic proteins that display a high turnover rate (MYC, MCL1). Cryo-electron microscopy (cryo-EM) is an advanced method that allows the visualization of human ribosome complexes with factors and bound inhibitors to improve our understanding of their functioning mechanisms mode. Cryo-EM structures could greatly assist the foundation phase of a novel drug-design strategy. One goal would be to identify new specific and active molecules targeting the ribosome in cancer such as derivatives of cycloheximide, a well-known ribosome inhibitor.

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“…3. Finds application in the treatment of chronic myeloid leukemia (CML) in both phases: chronic (CP) or accelerated (AP) 10 …”

Section: Materials Methodsmentioning

confidence: 99%

Determination of chiral bioactive molecules in Justicia adhatoda leaves by GC–MS

Das

Ghosh

2022

Chirality

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Chiral compounds find importance as drugs and therapeutic targets. Enantiomers of chiral drugs have been found to show different biological properties like pharmacokinetics, toxicology, pharmacology, metabolism, and so forth. In this study, we have identified the chiral compounds present in the medicinal plant Adhatoda vasica Nees (Justicia adhatoda Linn). Phytochemical investigation on the leaves of Justicia adhatoda resulted in the identification of 27 chiral compounds. We report diverse compounds identified in the crude methanolic extract of Justicia adhatoda leaves by GC-MS analysis exhibiting diverse biological activities. Quantitative analysis of anticancer compound dihydroxycolchicine from the methanolic extract of J. adhatoda leaves was done by external standard method, and the amount of anticancer compound dihydroxycolchicine was found to be 87.823 mg/l indicative of moderate production in the leaves. Therefore, the extract of leaves of Justicia adhatoda can be used as a potential source of chiral bioactive molecules of pharmacological importance for drug synthesis.

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Chemistry, Bioactivity, and the Structure-Activity Relationship of Cephalotaxine-Type Alkaloids From Cephalotaxus sp.

Cited by 23 publications

References 88 publications

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies

Determination of chiral bioactive molecules in Justicia adhatoda leaves by GC–MS

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