Chemistry and Biological Activities of Naturally Occurring and Structurally Modified Podophyllotoxins

Abstract

Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological activities of this class of compounds attracted attention worldwide. Currently, more than ninety natural podophyllotoxins were isolated, and structure modifications of these molecules were performed to afford a variety of derivatives, which offered optimized anti-tumor activity. This review summarized up to date reports on natural occurring podophyllotoxins and their sources, structural modification and biological activities. Special attention was paid to both structural modification and optimized antitumor activity. It was noteworthy that etoposide, a derivative of podophyllotoxin, could prevent cytokine storm caused by the recent SARS-CoV-2 viral infection.

Ultrasound-Assisted, BF3·OEt2-Promoted, Multicomponent Synthesis of Chromene-Based Podophyllotoxin Analogues

“…drugs due to their high cytotoxicity against various tumour cell lines. 16 Chromene derivative analogues of the podophyllotoxin lignan were first synthesised by Jurd (1997) 17 and later by Frackenpohl et al (2009) 18 using the procedure shown in Scheme 1. The derivatives were obtained in yields ranging from 5 to 35%.…”

“…These compounds were tested against various cancer cell lines and showed significant cytotoxicity comparable to their natural analogue, podophyllotoxin. 14,16 However, the low yields and lengthy process required to obtain these compounds present obstacles to conducting further in-depth studies with the tumour cell lines in which they were found to be active. 14,17,18 Scheme 1 Synthetic route used by Jurd (1997) 17 and Frackenpohl et al (2009) 18 Given the importance of these derivatives in developing new anticancer drugs, this work describes obtaining derivative 5 for the first time from a multicomponent reaction between tetronic acid 1, aromatic aldehyde 2, and a phenol 3 in the presence of an acid promoter.…”

“…14 Podophyllotoxin and its derivatives, such as apopycropodophyllotoxin and deoxypodophyllotoxin, are natural products of great interest for the development of anticancer drugs due to their high cytotoxicity against various tumour cell lines. 16…”

Scalemic natural products

“…12) and its analogues have been isolated in enantiopure form in not less than nine distinct and taxonomically unrelated plant families. 96…”

“…12) and its analogues have been isolated in enantiopure form in not less than nine distinct and taxonomically unrelated plant families. 96 The different enantiopurity of lignin and lignans is related to the cellular milieu where the monoelectronic oxidation takes place. The dimerization of monolignol, as exemplied by coniferyl alcohol ( 60) is initiated by a single-electron transfer catalysed by a laccase or a peroxidase (Scheme 14).…”