Jatrophane Diterpenoids With Protective Effect on Human Lymphocytes DNA

• Published in: Natural product communications Vol. 14; no. 5
• Main Authors: Krstić, Gordana, Jadranin, Milka, Stanković, Miroslava, Aljančić, Ivana, Vujisić, Ljubodrag, Mandić, Boris, Tešević, Vele
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.05.2019
• Subjects: SAR studies; human lymphocytes; MN; jatrophanes; CBMN assay; protective effect
• ISSN: 1934-578X; 1555-9475
• DOI: 10.1177/1934578X19848168

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).