Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones

Ren, Yulin; Kinghorn, A. Douglas

doi:10.1021/acs.jmedchem.0c01449

Cited by 31 publications

(37 citation statements)

References 316 publications

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“…Secondly, as mentioned in the introduction, natural products still lay the basis for the majority of novel anticancer therapeutics and several anticancer drugs currently on the market or in clinical trials are of plant origin [ 13 , 222 ]. Especially, semi-synthetic derivatives continuously reveal potent anticancer drugs and therefore are of ongoing interest and subject of recent studies and reports [ 223 , 224 ]. Another fact that becomes evident when looking at the literature on anticancer drugs is that various compound classes afford potent candidates [ 225 ], which was also a finding of the present review.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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“…Many lactones are known for their cytotoxicity in both healthy and tumor cells. Lactones occurring in nature become scaffolds for further synthesis of active compounds [ 29 ]. The cytotoxicity of artemisinin, a lactone of natural origin, was proven by Zheng.…”

Section: Cytotoxicity and Anticancer Activitymentioning

confidence: 99%

Biological Activity of Selected Natural and Synthetic Terpenoid Lactones

Surowiak

Balcerzak

Lochyński

et al. 2021

IJMS

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Terpenoids with lactone moieties have been indicated to possess high bioactivity. Certain terpenoid lactones exist in nature, in plants and animals, but they can also be obtained by chemical synthesis. Terpenoids possessing lactone moieties are known for their cytotoxic, anti-inflammatory, antimicrobial, anticancer, and antimalarial activities. Moreover, one terpenoid lactone, artemisinin, is used as a drug against malaria. Because of these abilities, there is constant interest in new terpenoid lactones that are both isolated and synthesized, and their biological activities have been verified. In some cases, the activity of the terpenoid lactone is specifically connected to the lactone moiety. Recent works have revealed that new terpenoid lactones can demonstrate such functions and are thus considered to be potential active agents against many diseases.

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“…Several other terpenoids, including pseudolaric acid, laurenditerpenol, and triptolide, reduced HIF‐1 expression in breast cancer cells (MDA‐MB‐468), T‐470, and myeloid leukemia cells (HL60A), respectively 133,155 …”

Section: Natural Products In Combating Lactate In Cancermentioning

confidence: 99%

Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

et al. 2021

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Anticancer drugs are not purely effective because of their toxicity, side effects, high cost, inaccessibility, and associated resistance. On the other hand, cancer is a complex public health problem that could intelligently adopt different signaling pathways and alter the body's metabolism to escape from the immune system. One of the cancer strategies to metastasize is modifying pH in the tumor microenvironment, ranging between 6.5 and 6.9. As a powerful determiner, lactate is responsible for this acidosis. It is involved in immune stimulation, including innate and adaptive immunity, apoptotic‐related factors (Bax/Bcl‐2, caspase), and glycolysis pathways (e.g., GLUT‐1, PKM2, PFK, HK2, MCT‐1, and LDH). Lactate metabolism, in turn, is interconnected with several dysregulated signaling mediators, including PI3K/Akt/mTOR, AMPK, NF‐κB, Nrf2, JAK/STAT, and HIF‐1α. Because of lactate's emerging and critical role, targeting lactate production and its transporters is important for preventing and managing tumorigenesis. Hence, exploring and developing novel promising anticancer agents to minimize human cancers is urgent. Based on numerous studies, natural secondary metabolites as multi‐target alternative compounds with health‐promoting properties possess more high effectiveness and low side effects than conventional agents. Besides, the mechanism of multi‐targeted natural sources is related to lactate production and cancer‐associated cross‐talked factors. This review focuses on targeting the lactate metabolism/transporters, and lactate‐associated mediators, including glycolytic pathways. Besides, interconnected mediators to lactate metabolism are also targeted by natural products. Accordingly, plant‐derived secondary metabolites are introduced as alternative therapies in combating cancer through modulating lactate metabolism and glycolytic pathways.

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Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones

Cited by 31 publications

References 316 publications

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Biological Activity of Selected Natural and Synthetic Terpenoid Lactones

Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

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