Cucurbitacin

Cucubita-5-ene with standard carbon numbering.

Cucurbitacin is any of a class of biochemical compounds that some plants — notably members of the family Cucurbitaceae, that includes the common pumpkins and gourds — developed in order to defend themselves from herbivores. Cucurbitacins are chemically classified as steroids, formally derived from cucurbitane, a triterpene hydrocarbon — specifically, from the unsaturated variant cucurbita-5-ene, or 19-(10→9β)-abeo-10α-lanost-5-ene. They often occur as glycosides.[1] They and their derivatives have been found in many plant families (including Brassicaceae, Cucurbitaceae, Scrophulariaceae, Begoniaceae, Elaeocarpaceae, Datiscaceae, Desfontainiaceae, Polemoniaceae, Primulaceae, Rubiaceae, Sterculiaceae, Rosaceae, and Thymelaeaceae), in some mushrooms (including Russula and Hebeloma) and even in some marine mollusks.

Cucurbitacins are generally cytotoxic and poisonous to some animals, and some of them are among the bitterest tastes to humans. Many have also been investigated for other biological activities.[2][3][4][5][6]

Biosynthesis

The biosynthesis of Cucurbitacin C has been described recently. Zhang et al. (2014) identified nine cucumber genes in the pathway for biosynthesis of cucurbitacin C and elucidated four catalytic steps.[7] These authors also discovered the transcription factors Bl (Bitter leaf) and Bt (Bitter fruit) that regulate this pathway in leaves and fruits, respectively. The Bi gene confers bitterness to the entire plant and is genetically associated with an operon-like gene cluster, similar to the gene cluster involved in thalianol biosynthesis in Arabidopsis. Fruit bitterness requires both Bi and the dominant Bt (Bitter fruit) gene. Nonbitterness of cultivated cucumber fruit is conferred by bt, an allele selected during domestication. Bi is a member of the oxidosqualene cyclase (OSC) gene family. Phylogenetic analysis showed that Bi is the ortholog of cucurbitadienol synthase gene CPQ in squash (Cucurbita pepo) [7]

Variants

The cucurbitacins include:

Cucurbitacin A

Cucurbitacin A

Cucurbitacin B

Cucurbitacin B

Cucurbitacin C

Cucurbitacin D

Cucurbitacin D

Cucurbitacin E

Cucurbitacin F

Cucurbitacin G

Cucurbitacin H

Cucurbitacin I

Cucurbitacin I

Cucurbitacin J

Cucurbitacin K

Cucurbitacin L

Cucurbitacin O

Cucurbitacin P

Cucurbitacin Q

Cucurbitacin Q

Cucurbitacin R

Cucurbitacin S

Cucurbitacin T

28/29 Norcucurbitacins

There are several substances that can be seen as derving from cucurbita-5-ene skeleton by loss of one of the methyl groups (28 or 29) attached to carbon 4; often with the adjacent ring (ring A) becoming aromatic.[1]:87–130

Other

Several other cucurbitacins have been found in plants.[1]:152–156,164–165

Occurrence

One of the active constituents of the colocynth fruit (Citrullus colocynthis) is a cucurbitacin.

The 2-O-β-D-glucopyranosides of Cucurbitacins K and L can be extracted with ethanol from fruits of Cucurbita pepo cv dayangua, at concentrations of 40 mg/15 kg and 32 mg/15 kg, respectively.[12]

Pentanorcucurbitacins A and B can be extracted with methanol from the stems of Momordica charantia, at concentrations of 1 mg/18 kg and 4.5 mg/18 kg, respectively.[8]

Cucurbitacins B and I, and derivatives of cucurbitacins B, D and E, can be extracted with methanol from dried tubers of Hemsleya endecaphylla at the concentrations shown above.[9]

Uses

Some cucurbitacins have the action of a potent cathartic purgative.

Some cucurbitacins and their derivatives are also cytotoxic. The toxicity of one cucurbitacin is enhanced by the introduction of a double bond at carbon C23, of an acetyl group at C25, or a double bond at carbons C1-C2. It is decreased by reduction of the ketone group at C3, or introduction of a hydroxyl group at C24. The compound cucurbitacin E is particularly cytotoxic; a concentration of 4.5×10−7μg/ml will destroy half of the cancer cells present.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 1.39 1.40 1.41 1.42 1.43 1.44 1.45 1.46 1.47 1.48 1.49 1.50 1.51 1.52 1.53 1.54 1.55 1.56 1.57 1.58 1.59 1.60 1.61 1.62 1.63 1.64 1.65 1.66 1.67 1.68 1.69 1.70 1.71 1.72 1.73 Jian Chao Chen, Ming Hua Chiu, Rui Lin Nie, Geoffrey A. Cordell and Samuel X. Qiu (2005), "Cucurbitacins and cucurbitane glycosides: structures and biological activities" Natural Product Reports, volume 22, pages 386-399 doi:10.1039/B418841C
  2. ↑ Alghasham, AA (2013). "Cucurbitacins - a promising target for cancer therapy". International journal of health sciences 7 (1): 77–89. PMC 3612419. PMID 23559908.
  3. ↑ Kapoor, S (2013). "Cucurbitacin B and Its Rapidly Emerging Role in the Management of Systemic Malignancies Besides Lung Carcinomas". Cancer biotherapy & radiopharmaceuticals 28 (4): 359. doi:10.1089/cbr.2012.1373. PMID 23350897.
  4. ↑ Ishii, T; Kira, N; Yoshida, T; Narahara, H (2013). "Cucurbitacin D induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial and ovarian cancer cells". Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 (1): 285–91. doi:10.1007/s13277-012-0549-2. PMID 23150173.
  5. ↑ Lui, VW; Yau, DM; Wong, EY; Ng, YK; Lau, CP; Ho, Y; Chan, JP; Hong, B; Ho, K; Cheung, CS; Tsang, CM; Tsao, SW; Chan, AT (2009). "Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells". Carcinogenesis 30 (12): 2085–94. doi:10.1093/carcin/bgp253. PMID 19843642.
  6. ↑ Sun, J; Blaskovich, MA; Jove, R; Livingston, SK; Coppola, D; Sebti, SM (2005). "Cucurbitacin Q: A selective STAT3 activation inhibitor with potent antitumor activity". Oncogene 24 (20): 3236–45. doi:10.1038/sj.onc.1208470. PMID 15735720.
  7. ↑ 7.0 7.1 Zhang, Y. et al. (2014) Biosynthesis, regulation, and domestication of bitterness in cucumber. Science 346 (6213): 1084
  8. ↑ 8.0 8.1 8.2 Chiy-Rong Chen, Yun-Wen Liao, Lai Wang, Yueh-Hsiung Kuo, Hung-Jen Liu, Wen-Ling Shih, Hsueh-Ling Cheng and Chi-I Chang (2010). "Cucurbitane Triterpenoids from Momordica charantia and Their Cytoprotective Activity in tert-Butyl Hydroperoxide-Induced Hepatotoxicity of HepG2 Cells". Chemical & pharmaceutical bulletin, volume 58, issue 12, pages 1639-1642. doi:10.1248/cpb.58.1639
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Jian-Chao Chen, Gao-Hong Zhang, Zhong-Quan Zhang, Ming-Hua Qiu, Yong-Tang Zheng, Liu-Meng Yang, Kai-Bei Yu (2008), "Octanorcucurbitane and Cucurbitane Triterpenoids from the Tubers of Hemsleya endecaphylla with HIV-1 Inhibitory Activity". J. Nat. Prod. volume 71, pages 153–155 doi:10.1021/np0704396
  10. ↑ 10.0 10.1 10.2 10.3 FT Halaweish, DW Tallamy. 1993. A new cucurbitacin profile for Cucurbita andreana: A candidate for cucurbitacin tissue culture. Journal of Chemical Ecology 19(6):1135-1141. http://link.springer.com/article/10.1007%2FBF00987375
  11. ↑ http://www.sciencedirect.com/science/article/pii/S0031942200942237
  12. ↑ 12.0 12.1 12.2 Da-Cheng Wang, Hong-Yu Pan, Xu-Ming Deng, Hua Xiang, Hui-Yuan Gao, Hui Cai, and Li-Jun Wu (2007), "Cucurbitane and hexanorcucurbitane glycosides from the fruits of Cucurbita pepo cv dayangua". Journal of Asian Natural Products Research, volume 9, issue 6, pages 525–529.