Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids

Abstract

Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N -heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure–activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery.

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

“…(-)-Antofine (Figure 4), a phenanthroindolizidine alkaloid, is extracted from the plants of the Asclepiadaceae family, such as Tylophora, Cynanchum, and Pergularia. (-)-Antofine has previously exhibited antiviral, antimicrobial, and anticancer activities [236,237]. In a study performed by Song et al [116], (-)-antofine was found to decrease cell growth in Caki-1 (clear cell RCC) cell lines.…”

Tandem Ene/[4 + 2] Cycloaddition Reaction for the Synthesis of 9-Benzylphenanthrenes from Arynes and α-(Bromomethyl)styrenes

“…1 A wide range of biological activities are exhibited by phenanthrene derivatives, including anti-inflammatory, 2 antimicrobial, 3 anticancer, 4 antitumor, and antiviral activities. 5 Accordingly, considerable effort has been spent on designing methods for the construction of the phenanthrene skeleton. 6 Classical synthesis methods include organocatalytic approaches, 7 metal-catalyzed cyclization, 8 isomerization/arylation, 9 and skeletal rearrangement.…”

“…Phenanthrene is a polycyclic aromatic structure that occurs within many natural products, pharmaceuticals, and organic materials . A wide range of biological activities are exhibited by phenanthrene derivatives, including anti-inflammatory, antimicrobial, anticancer, antitumor, and antiviral activities . Accordingly, considerable effort has been spent on designing methods for the construction of the phenanthrene skeleton .…”

(R)-13aα-Densiindolizidine, A New Phenanthroindolizidine Alkaloid From Cryptocarya densiflora Blume (Lauraceae) and Molecular Docking Against SARS-CoV-2

“…12 Since the first isolation of tylophorine in 1935, 13 phenanthroindolizidine alkaloids have attracted much attention because they exhibited antitumor and anticancer activity, as well as inhibitors of protein synthesis. 14 More than 100 natural phenanthroindolizidines have been reported to date. Antofine has been extensively studied towards the development of potent anticancer agent due to its excellent cytotoxic activity.…”

“…Antofine has been extensively studied towards the development of potent anticancer agent due to its excellent cytotoxic activity. 14,15 In addition, several phenanthroindolizidine alkaloids such as tylophorine, tylophorinine and 7-methoxycryptopleurine have been reported to display potency against SARS-CoV-2 and transmissible gastroenteritis virus (TGEV) in vitro at low nanomolar level with high oral availability in rats. These suggested they could be used as potential therapeutic agents for coronavirus infections.…”