In vitro antituberculosis activity of diterpenoids from the Vietnamese medicinal plant Croton tonkinensis

Abstract

Diterpenoids from the Vietnamese medicinal plant Croton tonkinensis are rich in ent-kaurane, kaurane and the grayanane class and are valuable intermediate plant metabolites with different bioactivities. In this study, we report the antituberculosis activity of these diterpenoids against both susceptible and resistant strains of M. tuberculosis for the first time. All of the ent-kaurane, kaurane and grayanane diterpenoids showed high to moderate activity against Mycobacterium. The highest antituberculosis activity was observed for ent-1β,7α,14β-triacetoxykaur-16-en-15-one (cpp604), with MIC values of 0.78, 1.56 and 3.12-12.5 µg/ml against H37Ra, H37Rv and all other resistant strains of Mycobacterium tuberculosis examined. In addition, other ent-kaurane-type diterpenoids also showed very high activities against mycobacterium, including cpp609 (1.56 µg/ml), cpp610 (1.56 µg/ml), cpp601 (3.12-6.25 µg/ml), cpp602 (3.12-6.25 µg/ml), cpp607 (3.12-6.25 µg/ml) and cpp608 (3.12-6.25 µg/ml). From the structure-activity relationship, functional groups R3 and R5 of the ent-kaurane skeleton were found to modulate the antimycobacterial activity.

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

“…The highest antituberculosis activity was observed for ent-1β,7α,14β-triacetoxykaur-16-en-15-one 170, with MIC 0.78,1.56 and 3.12–12.5 μg mL −1 against H37Ra, H37Rv and all other resistant strains of M. tuberculosis examined. 97 Ethyl p -methoxycinnamate (EPMC) 185, isolated from Kaempferia galanga , was shown to inhibit M. tuberculosis H37Ra, H37Rv, drug susceptible and MDR clinical isolates (MIC 0.242–0.485 mM). 98 Plumericin 186, showed better activity against pan sensitive as well as four MDR strains of M. tuberculosis with MIC values of 2.1 ± 0.12, 1.3 ± 0.15, 2.0 ± 0.07, 1.5 ± 0.13, and 2.0 ± 0.14 μg mL −1 and MBC 3.6 ± 0.22, 2.5 ± 0.18, 3.8 ± 0.27, 2.9 ± 0.20, and 3.7 ± 0.32 μg mL −1 than isoplumericin 187, respectively, isolated from Plumeria bicolor .…”

New Terpenoids from the Corticioid Fungus Punctularia atropurpurascens and their Antimycobacterial Evaluation

“…Only 29 %, 49 %, and 28 % of inhibition of the mycobacteria was observed at 50 µg/mL of 1, 2, and 3, respectively. Few drimanes from medicinal Warburgia species [13][14][15] and the basidiomycete Poria albocincta BCC 26 244 [16], and kauranes from the herb Isodon rubescens [17,18] and the Vietnamese medicinal plant Croton tonkinensis [19], have been tested for their antimycobacterial potential.…”

New Compounds and Potential Candidates for Drug Discovery from Medicinal Plants of Vietnam

“…78) ent-Kauranes with a 15-oxo-16-ene moiety also induced the apoptosis of colorectal cancer cell lines, Caco-2 and LS180, and enhanced the generation of intracellular ROS in both cell types. 79) The new cycloartanes 40 and 41 from M. macrostachyus showed cytotoxicity against the human cancer cell lines KB and LU-1 (lung adenocarcinoma) with IC 50 values ranging from 4.31±0.09 to 7.12±0.07 µg/mL. 27) 3-Deoxycardiobutanolide (56) from G. macrocalyx was found to have potent cytotoxicity (IC 50 value of 0.09 µM) against HL-60 (human promyelocytic leukemia) cell lines, but no inhibitory activity against the KB cell line (IC 50 >20 µM).…”

“…ent-Kaurane diterpenoids with an α,β-unsaturated ketone in the D ring 1 (IC 50 3.12-6.25 µg/mL), 2 (IC 50 3.12-6.25 µg/mL), 4 (IC 50 3.12-6.25 µg/mL), and 14 (IC 50 1.56 µg/mL) showed high activities against Mycobacterium. 80) 3.9. Anti-diabetic Activity Oblongixanthones G (69) and H (70) displayed potent α-glucosidase inhibitory activity (IC 50 9.4±1.8 and 21.2±9.7 µM, respectively) but weak PTP1B (protein-tyrosine phosphatase 1B) inhibitory activity (IC 50 94.8±12.0 and 82.4±6.8 µM, respectively).…”