Jatrophane Diterpenoids With Protective Effect on Human Lymphocytes DNA

Abstract

Two sets of structurally different jatrophanes (1-11 and 13-16), jatrophane 12, and latex extract of 2 Euphorbia species (17 and 18) were tested for in vitro protective effect against chromosome aberrations in peripheral human lymphocytes using the cytokinesis-block micronucleus (CBMN) assay. Jatrophanes 1-6 in minimal doses of 1 µg/mL prominently decreased micronuclei (MN) frequency in the range 44.86% to 34.29% and manifested considerable protective effect. From the other set of jatrophanes, 13 in the same minimal dose notably decreased MN frequency by 31.05%, while extracts 17 and 18 at a concentration of 4 µg/mL remarkably decreased the frequency of MN by 37.94% and 36.12%, respectively. Jatrophanes 12, 14, and 16 showed moderate protection, while 7-11 and 15 were less active than positive control. The structure-activity relationship (SAR) studies of the tested jatrophanes (1-16) indicated the favorable position of benzoate at C-8 or C-9 (3, 4, and 13) and a preference of isobutanoyloxy group at C-3 (1-3) rather than propanoyloxy at the same position (4-6) for pronounced protective effect on human lymphocytes DNA. In a previous SAR study on 11 jatrophanes (1, 3-8, and 13-16), the same structural features in 3, 4, and 13 influenced powerful inhibition of P-gp, while growth inhibition of cancer cells was more than doubled in 1 (isobutanoyloxy group at C-3) compared to 6 (propanoyloxy at C-3).

DNA protective activity of triterpenoids isolated from medicinal mushroom Fomitopsis betulina

“…slightly decreases, which was not the case with the previously studied jatrophanes and sesquiterpene lactones (Krstić et al 17 and Cvetković et al 18 , respectively). Typical DNA protective activity of natural products is mostly attributed to their antioxidative potential.…”

“…Typical DNA protective activity of natural products is mostly attributed to their antioxidative potential. [15][16][17][18] The cytotoxic and antioxidant activity of nine lanostane-type triterpenes, isolated from P. cocos, were examined previously by Zhou et al 20 They tested the ability of scavenging free oxygen radicals and inhibition of oxidation using DPPH (2,2-diphenyl-1-picrylhydrazyl) radical test. In comparison to the vitamin E used as a positive control, the compounds tested did not show antioxidant activity with p<0.05 that may be considered statistically significant.…”

“…The application of CBMN assay for antioxidant evaluation of heterocyclic compounds is well known. [15][16][17][18] Hitherto, the antioxidant capacity of lanostanes is questionable and depends on the applied test. 19,20 A potential of the lanostanes as DNA protecting agents, as well as the possible mechanism of their action is discussed.…”

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

“…135,341 Among them, euphodendrophanes A ( K57 ), B ( K58 ), H ( 414 ), I ( 415 ), K ( 418 ), and O ( 422 ), prominently decreased micronuclei frequency and manifested considerable protective effect. 342 Euphorbesulin G ( 465 ) displayed potent antimalarial effect against chloroquine-resistant Plasmodium falciparum strain with an IC 50 value of 0.12 μM. 111…”

Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship

“…These observations agreed with Kulig et al’s [ 111 ] assertion that vicinal diol groups contribute significantly to the bioactivities of naturally occurring compounds possessing them. Other studies on the structure–activity relationship of jatrophane diterpenoids showed that substitution of a benzoate at C-8 and C-9 are favorable, while isobutanoyloxy group substitution at C-3 increased the observable effects on human lymphocytes deoxyribonucleic acid (DNA) [ 112 ].…”