Cancer Treatment by Caryophyllaceae-Type Cyclopeptides

Abstract

Cancer is one of the leading diseases, which, in the most cases, ends with death and, thus, continues to be a major concern in human beings worldwide. The conventional anticancer agents used in the clinic often face resistance among many cancer diseases. Moreover, heavy financial costs preclude patients from continuing treatment. Bioactive peptides, active in several diverse areas against man's health problems, such as infection, pain, hypertension, and so on, show the potential to be effective in cancer treatment and may offer promise as better candidates for combating cancer. Cyclopeptides, of natural or synthetic origin, have several advantages over other drug molecules with low toxicity and low immunogenicity, and they are easily amenable to several changes in their sequences. Given their many demanded homologues, they have created new hope of discovering better compounds with desired properties in the field of challenging cancer diseases. Caryophyllaceae-type cyclopeptides show several biological activities, including cancer cytotoxicity. These cyclopeptides have been discovered in several plant families but mainly are from the Caryophyllaceae family. In this review, a summary of biological activities found for these cyclopeptides is given; the focus is on the anticancer findings of these peptides. Among these cyclopeptides, information about Dianthins (including Longicalycinin A), isolated from different species of Caryophyllaceae, as well as their synthetic analogues is detailed. Finally, by comparing their structures and cytotoxic activities, finding the common figures of these kinds of cyclopeptides as well as their possible future place in the clinic for cancer treatment is put forward.

Keywords: Caryophyllaceae-type cyclopeptides; anticancer activity; dianthins; longicalycinin A; plant family; synthetic analogues.

Chart 1

Inhibitory action of segetalin E against cancer cells.

Figure 1

Structure of segetalin E.

Figure 2

The structure of yunnanin A and its designed analogue.

Chart 2

Inhibitory action of the yunnanin A analogue against cell lines.

Figure 3

The structures of yunnanin B, C, D.

Chart 3

Anticancer activity of dichotomins on p-388 cells.

Figure 4

The structures of dichotamins.

Chart 4

Inhibitory activity of cycloleonuripeptides on p-338 lymphocytic leukemia cells.

Figure 5

The structures of cycloleonuripeptides A, (B,C) (R=O). B and C are isomers.

Chart 5

Antiproliferative activity of cyclolinopeptides on mouse lymphocyte cells.

Figure 6

The structures of cyclolinopeptides.

Figure 7

The structures of cherimolacyclopeptides.

Chart 6

Cytotoxic activity of cherimolacylopeptides on KB tumor cells.

Figure 8

The structures of Dianthins.

Figure 9

Structure of Longicalycinin A.

Chart 7

Cytotoxicity of longicalycinin A, compared with dianthin A and 5- Fluorouracil (5-FU) as standard drug on cancer cells, Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC).

Chart 8

Cytotoxicity of longicalycinin A on cancer cells, HepG2, compared with dianthin E and doxorubicin (as standard drug).

Figure 10

Caryophyllaceae-type cyclopeptides, isolated from the ethanol extract of various higher plants of Caryophyllaceae type and their cancer cell cytotoxicity.