Bioactive Constituents of Indigofera spicata

Abstract

Four new flavanones, designated as (+)−5″-deacetylpurpurin (1), (+)−5-methoxypurpurin (2), (2S)-2,3-dihydrotephroglabrin (3), and (2S)-2,3-dihydrotephroapollin C (4), together with two known flavanones (5 and 6), three known rotenoids (7–9), and one known chalcone (10) were isolated from a chloroform-soluble partition of a methanol extract from the combined flowers, fruits, leaves, and twigs of Indigofera spicata, collected in Vietnam. The compounds were obtained by bioactivity-guided isolation using HT-29 human colon cancer, 697 human acute lymphoblastic leukemia, and Raji human Burkitt’s lymphoma cell lines. The structures of 1–4 were established by extensive 1D- and 2D-NMR experiments and the absolute configurations were determined by the measurement of specific rotations and CD spectra. The cytotoxic activities of the isolated compounds were tested against the HT-29, 697, Raji and the CCD-112CoN human normal colon cells. Also, the quinone reductase induction activities of the isolates were determined using the Hepa 1c1c7 murine hepatoma cell line. In addition, cis-6aβ−12aβ-hydroxyrotenone (7) was evaluated in an in vivo hollow fiber bioassay using HT-29, MCF-7 human breast cancer, and MDA-MB-435 human melanoma cells.

Investigation of Vietnamese plants for potential anticancer agents

“…Three new flavanones, (+)-5-methoxypurpurin ( 40 ), (2 S )-2,3-dihydrotephroglabrin ( 41 ), and (2 S )-2,3-dihydrotephroapollin C ( 42 ), isolated from Indigofera spicata , showed cancer chemopreventive potential by inducing quinone reductase activity, a phase II metabolizing enzyme, in Hepa 1c1c7 murine hepatoma cells (Bueno Pérez et al 2013). The structures of the new compounds were determined by NMR data interpretation and comparison of their chemical shifts to the values of closely related analogues reported previously in the literature (Abd El-Razek et al 2007; Rao and Raju 1984; Waterman and Khalid 1980).…”

“…The structures of the new compounds were determined by NMR data interpretation and comparison of their chemical shifts to the values of closely related analogues reported previously in the literature (Abd El-Razek et al 2007; Rao and Raju 1984; Waterman and Khalid 1980). In addition, the 1 H-NMR data of compounds 40–42 showed typical signals for the presence of a flavanone nucleus with resonances around δ H 5.5 (H-2), 2.9 (H-3 a ), and 3.0 (H-3 b ) ppm (Bueno Pérez et al 2013). The absolute configuration assignments were based on circular dichroism and specific rotation measurements.…”

“…The absolute configuration assignments were based on circular dichroism and specific rotation measurements. Compounds 40–43 and 48 were active with CD (concentration required to double quinone reductase activity) values of less than 10 μM and low toxicity to cells with IC 50 values greater than 20 μM (Bueno Pérez et al 2013). Furthermore, the new flavanone 40 exhibited a low CD value of 0.2 μM and a high IC 50 and CI (chemopreventive index = IC 50 /CD) values of 63.9 μM and 376.7, respectively, demonstrating this new compound to be an interesting new lead as a cancer chemopreventive agent (Bueno Pérez et al 2013).…”

“…Compounds 40–43 and 48 were active with CD (concentration required to double quinone reductase activity) values of less than 10 μM and low toxicity to cells with IC 50 values greater than 20 μM (Bueno Pérez et al 2013). Furthermore, the new flavanone 40 exhibited a low CD value of 0.2 μM and a high IC 50 and CI (chemopreventive index = IC 50 /CD) values of 63.9 μM and 376.7, respectively, demonstrating this new compound to be an interesting new lead as a cancer chemopreventive agent (Bueno Pérez et al 2013). In addition, compound 40 showed more potent induction activity with much lower toxicity to cells than the positive control, L-sulforaphane (CD = 0.5 μM, IC 50 = 12.1 μM, and CI = 23.9), a well-known monofunctional inducer of quinone reductase obtained from broccoli (Bueno Pérez et al 2013; Zhang et al 1992).…”

“…The known compounds rocaglaol ( 7 ), methyl rocaglate ( 8 ) and five other known rocaglate derivatives ( 4–6, 9–10 ), four known cucurbitacins, cucurbitacin D ( 36 ), 3- epi- isocucurbitacin D ( 37 ), 25- O -acetylcucurbitacin F ( 38 ), cucurbitacin I ( 39 ), and two known rotenoids, cis -(6a β ,12a β )-hydroxyrotenone ( 44 ) and rotenone ( 45 ) were also found to exhibit potent cytotoxicity against HT-29 cells with IC 50 values of less than 1 μM (Bueno Pérez et al 2013; Pan et al 2012; Pan et al 2013). Compounds 5 and 9 showed particularly potent activity against HT-29 cells with IC 50 values of 0.002 and 0.0007 μM, respectively, and were comparable in potency to the positive control, paclitaxel, which gave an IC 50 value of 0.001 μM (Pan et al 2013).…”