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Review
. 2020 Jan-Feb:38:107337.
doi: 10.1016/j.biotechadv.2019.01.004. Epub 2019 Jan 8.

Current status and contemporary approaches to the discovery of antitumor agents from higher plants

Garima Agarwal  1 , Peter J Blanco Carcache  1 , Ermias Mekuria Addo  1 , A Douglas Kinghorn  2
Affiliations
Review

Current status and contemporary approaches to the discovery of antitumor agents from higher plants

Garima Agarwal et al. Biotechnol Adv. 2020 Jan-Feb.

Abstract

Higher plant constituents have afforded clinically available anticancer drugs. These include both chemically unmodified small molecules and their synthetic derivatives currently used or those in clinical trials as antineoplastic agents, and an updated summary is provided. In addition, botanical dietary supplements, exemplified by mangosteen and noni constituents, are also covered as potential cancer chemotherapeutic agents. Approaches to metabolite purification, rapid dereplication, and biological evaluation including analytical hyphenated techniques, molecular networking, and advanced cellular and animal models are discussed. Further, enhanced and targeted drug delivery systems for phytochemicals, including micelles, nanoparticles and antibody drug conjugates (ADCs) are described herein.

Keywords: 2D and 3D cell cultures; Antibody-drug conjugates (ADCs).; Botanical dietary supplements; Cancer chemotherapeutic agents; Dereplication analytical methods; Micelles; Molecular networking; Nanoparticles; Plant natural products.

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Figures

Figure 1.
Figure 1.
Plant-derived natural products used as antitumor drugs
Figure 2.
Figure 2.
Examples of other plant-derived secondary metabolites and selected derivatives with antitumor activity
Figure 3.
Figure 3.
Examples of bioactive xanthones from mangosteen (Garcinia mangostana)
Figure 4.
Figure 4.
Selected chemical constituents of noni (Morinda citrifolia)
Figure 5
Figure 5
Summary of advantages and disadvantages of using 2D cell culture
Figure 6.
Figure 6.
Summary of advantages and disadvantages of using 3D cell culture
Figure 7.
Figure 7.
Examples of micelle designs
Figure 8.
Figure 8.
Major components of ADCs. Included is each component’s main purpose, requirements to be a candidate for an ADC, and some examples based on approved ADCs (Note: the purpose, requirements and examples stated are not comprehensive but only representative of the most common ones; see the cited references for additional information).
Figure 9.
Figure 9.
A) Structure of maytansine and analogues (DM1 and DM4) common in ADCs. B) Structure of ado-trastuzumab emtansine (Kadcyla®) (Note: the n, i.e., DAR, given is an approximate value and may vary).
Figure 10.
Figure 10.
A) Structure of silvestrol. B) ADCs (ADC-103 and ADC-104) conjugated at position 2 of silvestrol. C) ADCs (ADC-105 and ADC-108) conjugated at position 6′′′ of silvestrol.
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