Synthesis of Trinorditerpenoid Derivatives and Evaluation of Antimicrobial and Cytotoxic Activity

Abstract

The synthesis of optically active trinorditerpenes was carried out, and their antimicrobial and antitumor activity was tested. The synthetic derivative 12-hydroxypodocarpa-8,11,13-triene (7) showed GI 50 at 6.6 µM against breast cancer . 11, showed GI 50 at 12.1 µM against leukemia RPMI-8226 (LC 50 = 76.1 µM and log 10 GI 50 = -4.92).Key words: trinorditerpenoid derivatives, antimicrobial and cytotoxic activity.The trinorditerpenes have attracted the interest of natural product chemists during the past decades. In this context, simple and sequential modifications were performed on the methyl O-methylpodocarpane molecule (1) because it is a chiral starting material for the synthesis of diterpenoids with biological activity [1-3]. Our goal was to make this class of trinorditerpenoids readily available for the investigation of the basic structural requirements to explore the antimicrobial and antitumor activity.The compounds synthesized by us were evaluated for their antimicrobial activity in a preliminary screening. We observed that the compound 7 showed activity against Gram-positive bacteria, Gram-negative bacteria, yeast, and mold (Table 1). This particular antimicrobial ability attracted our attention to the compound 7 since it has a more simple structure than the other compounds reported here. Of the eight compounds reported here, four were accepted and tested at the National Institute of Health (NIH), Developmental Therapeutics Program (DTP), to evaluate the antitumor activity, where the 12-hydroxypodocarpa-8,11,13-triene (7) showed GI 50 at 11.3 µM against melanoma SK-MEL5 (LC 50 = 48.3 µM and log 10 GI 50 = -4.95). The 12-acetyloxypodocarpa-8,11,13-triene (8) showed GI 50 at 12.1 µM against leukemia RPMI-8226 (LC 50 = 76.1 µM and log 10 GI 50 = -4.92).i.

Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities

“…Furthermore, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17) was evaluated for its apoptosis-inducing activity. Furthermore, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17) was evaluated for its apoptosis-inducing activity.…”

“…This was confirmed by the downfield chemical shifts of C(9) (d(C) 56.0 -57.6) and C(12) (d(C) 27.0 -49.4) compared to compound 4. The 13 C-NMR signals due to C(16) and C (17), were found at d(C) 79. 2) further demonstrated compound 1 was 11-hydroxy substitute of compound 4.…”

“…(Asteraceae) is a marine mangrove associated plant, distributed in the coastal areas of Fujian Province in P. R. China. Kaurenoic acid (3) is an ent-kaurane diterpenoid, [6] [7] which is claimed to have many biological activitiesmainly antimicrobial, [14] antibacterial, [15] cytotoxic, [16] [17] antiinflammatory, [18] and anticonvulsant properties. [1] [2] Chemical and biological studies of Wedelia species have led to the isolation of many kaurenoid diterpenes and eudesmanolide sesquiterpenes.…”