Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy

Abstract

The phenanthroindolizidine and phenanthroquinolizidine alkaloids, typified by tylophorine and cryptopleurine, are a family of plant-derived small molecules with significant therapeutic potential. The plant extracts have been used in herbal medicine and the isolated compounds have displayed a range of promising therapeutic activity such as anti-ameobicidal, anti-viral, anti-inflammatory and anti-cancer activity. Despite their therapeutic protential, no compounds in this class have fully passed clinical trials. Drawbacks include low in vivo anti-cancer activity, central nervous system toxicity and low natural availability. A number of biological effects of these compounds, such as protein and nucleic acid synthesis suppression, have been identified, but the specific biomolecular targets have not yet been identified. Significant effort has been expended in the synthesis and structure-activityrelationship (SAR) studies of these compounds with the hope that a new drug will emerge. This review will highlight important contributions to the isolation, synthesis, SAR and mechanism of action of the phenanthroindolizidine and pheanthroquinolizidine alkaloids.

Evolution of copper(II) as a new alkene amination promoter and catalyst

“…We further demonstrated the utility of this methodology in the enantioselective total synthesis of ( S )-(+)-tylophorine ( 46 ), a promising anti-cancer compound with excellent in vitro activity in a broad range of cancer cell lines [37,38]. Our synthesis (Scheme 8) of tylophorine is 8 steps from commercially available starting material, making this enantioselective synthesis one of the shorter preparations of this compound [38].…”

“…Our synthesis (Scheme 8) of tylophorine is 8 steps from commercially available starting material, making this enantioselective synthesis one of the shorter preparations of this compound [38]. …”

Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

“…The phenanthroindolizidine alkaloids, such as tylophorine, tylocrebrine, and tylophorinine, are characteristic constituents of Cynanchum, Pergularia, Tylophora, and other genera of the Asclepiadaceae. These phenanthroindolizidines have activities against leukemia, asthma, anaphylaxis, other inflammations and bacterial infection (Bhutani et al, 1987;Chemler, 2009;Gopalakrishnan et al, 1980), as well as against cancer Li et al, 2001b;Staerk et al, 2002;Yang et al, 2006Yang et al, , 2007a. The herbal plant Tylophora indica has been traditionally used in India as a folk remedy to treat bronchial asthma, bronchitis, rheumatism, and dermatitis (Li et al, 2001a).…”

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

“…Many of these alkaloids possess significant anticancer activity (both in vitro and in vivo) as well as anti-inflammatory, antiameobicidal, and antiviral activities [2]. The significant antineoplastic activities of many phenanthroindolizidines have attracted the interest of quite a number of medicinal chemists and pharmacologists since 1935 when the first phenanthroindolizidine alkaloid, tylophorine, was isolated from Tylophora indica [3].…”