Potential Anticancer Agents Characterized from Selected Tropical Plants

Abstract

Higher plants are well known for their value in affording clinically useful anticancer agents, with such compounds acting against cancer cells by a range of mechanisms of action. There remains a strong interest in the discovery and development of plant secondary metabolites as additional cancer chemotherapeutic lead compounds. In the present review, progress on the discovery of plant-derived compounds of the biflavonoid, lignan, sesquiterpene, steroid, and xanthone structural types is presented. Several potential anticancer leads of these types have been characterized from tropical plants collected in three countries as part of our ongoing collaborative multi-institutional project. Preliminary structure-activity relationships and work on in vivo testing and cellular mechanisms of action are also discussed. In addition, the relevant work reported by other groups on the same compound classes is included herein.

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer

“…Xanthones, such as α-mangostin, mediate cytotoxicity mainly via cell cycle arrest and reactive oxygen species (ROS)-induced apoptosis (16). The anticancer effects and molecular mechanisms of polyphenols are reported to be associated with their chemical constitution which is necessary for its anticancer activities, such as the C-3 prenylation of benzoxanthone-type prenylated flavonoids, C-1 hydroxy group and isoprenyl group at C-8 of prenylated xanthones, the C-2 carbonyl group, C-4 prenyl group and pyran ring connected at the C-2 and C-3 of caged xanthones (9). Anticarcinogenic activities of polyphenols include suppressing the proliferation, differentiation, metastasis, and angiogenesis of various kinds of cancer cells through inhibiting several kinases involved in signal transduction (17–20).…”

“…Alkaloids and polyphenols are significantly dominant among cancer therapeutics (7, 8). Recently, the targets and mechanisms of plant-derived anticancer agents have been widely reported (9). In this review, we will focus on advances in knowledge about the signaling pathways affected by plant-derived natural products.…”

Natural and Synthetic Lactones Possessing Antitumor Activities

“…Cancer is frequently correlated with disruption in key signaling pathways, which involve extracellular ligands, transmembrane receptors, intracellular signaling protein kinases, and transcription factors, causing aberrant cell proliferation and defective apoptosis induction [ 3 , 4 ]. Recently, the targets and molecular mechanisms of natural product-derived anticancer agents have been extensively investigated [ 5 , 6 ]. Furthermore, the effort has eventually led to the emergence of various natural lactones and their derivatives as potential lead compounds for anticancer therapeutics on account of their potent bioactivities, including cytotoxicity against cancer cells and anti-neoplastic efficacy in in vivo studies [ 7 , 8 , 9 ].…”

Transition Metal-Mediated Annulation Approaches for Synthesis of Arylnaphthalene Lignan Lactones

“…Natural arylnaphthalene lignan lactones are classified as lignans and isolated from a variety of dietary or medicinal plants, such as Phyllanthus, Justicia, Hapllophyllum , and Cleistanthus (Anjaneyulu et al, 1981 ; Batsuren et al, 1981 ; Khalid and Waterman, 1981 ; Ulubelen, 1985 ; Lin et al, 1995 ). They show broad pharmacological activities, including cytotoxic (Day et al, 2002 ; Yu et al, 2010 ; He et al, 2012 ; Deng et al, 2014 ; Luo et al, 2014 ; Ren et al, 2014 , 2019 ; Won et al, 2015 ; Woo et al, 2017 ; Woodard et al, 2018 ; Yi et al, 2018 ; Young et al, 2018 ), antiplatelet (Chen et al, 1996 ; Weng et al, 2004 ), neuroprotective (Gu et al, 2016 ), antiviral (Asano et al, 1996 ; Cow et al, 2000 ), antifungal (Windayani et al, 2014 ), and anti-HIV (Chang et al, 1995 ; Zhang et al, 2017 ) activities. From the biosynthetic viewpoint, oxygenated phenylpropanoids, which are synthesized from phenylalanine or tyrosine, are condensed to bicyclic diphenyl furofurans.…”