Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri)

Abstract

A major problem in the management of visceral leishmaniasis, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy, indicating the urgent need to identify new antileishmanial compounds. This study was undertaken to evaluate the antileishmanial activity of the fruit rind of Myristica malabarica that is used as a spice and is also credited with medicinal properties. The antipromastigote activity of different extracts/fractions of M. malabarica and its constituent diarylnonanoids were evaluated in Leishmania donovani promastigotes (MHOM/IN/83/AG83) using the MTS-PMS assay. Preliminary screening of the ether extract (R1) with its crude methanol fraction (R2) and two fractions (R3 and R4) revealed that R2 had potent leishmanicidal activity (IC(50) 31.0 microg/mL), whereas R3 and R4 showed poor activity. Fractionation of R2 yielded four diarylnonanoids (malabaricones A-D, designated as Mal A, Mal B, Mal C and Mal D, respectively). The IC(50) values of Mal A-D were 16, 22, 27 and >50 microg/mL, respectively. Taken together, the data suggest that the methanol extract of M. malabarica, especially its constituent compounds, Mal A and Mal B, have promising antileishmanial activity meriting further investigations regarding the underlying molecular mechanism(s) of action with a view towards future drug development.

Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-κB pathway

“…The chemical structures of CHV and APC are shown in Fig. 1 (m, 1H), 6.59-6.79 (m, 3H); 13 The LAL assay confirmed that endotoxin is practically absent in APC.…”

“…Cytotoxicity assay RAW 264.7 cells (2 × 10 5 /200 µl/well) were seeded in 96 well tissue culture plates and allowed to adhere for 1-3 h at 37°C, 5% CO 2 . Following addition of APC (0-25 µg/ml), the cells were incubated for 48 h and the MTS-PMS assay was performed [13].…”

Nematicidal activity of malabaricones isolated from Myristica malabarica fruit rinds against Bursaphelenchus xylophilus

“…Even though the presence of a hydroxyl group in ring B was not essential for their nematicidal activity, increase in the number of hydroxyl groups in ring B was associated with increasing nematicidal activity. Sen et al (2007) reported a reverse trend in the antileishmanial activity of malabacones A, B, C and D; resorcinols with higher hydroxyl groups in ring B showed lower antileishmanial activity. On the other hand, Park et al (2005) found that cinnamyl acetate and diallyl trisulphide with higher molecular weights were more effective against pine wood nematode than cinnamyl aldehyde and diallyl disulphide, respectively.…”

“…The three compounds were identified as malabaricones A, B and C. The resorcinols have been detected in M. malabarica (Sen et al, 2007), Myristica cagayanesis (Kuo et al, 1989), Myristica gigantean (Pharm et al, 2002), Myristica maingayi (Pharm et al, 2000) and Myristica fragrans (Orabi et al, 1991). As for the biological activities of malabaricones, they have been reported to have antioxidant (Patro et al, 2005), arg-gingipain inhibitory (Shinohara et al, 1999), antimicrobial (Orabi et al, 1991;Shinohara et al, 1999) and antipromastigote (Sen et al, 2007) activities. However, there is little information about the nematicidal activity of malabaricones against nematodes, including pine wood nematode.…”

A new acyclic diterpene acid and bioactive compounds from Knema glauca

“…Both the acylresorcinols 1 and 6 and the acylphloroglucinols 7 and 8 were differently cytotoxic to the cell lines tested, although none of them were strongly active. Malabaricone A (6), which has been shown to possess nematocidal (Hosoi et al, 1999) and antileishmanial activities (Sen et al, 2007), exhibited antimalarial activity against the protozoa Plasmodium falciparum with an IC 50 value of 2.78 µg/mL. The compound was weakly active against herpes simplex virus type 1; whereas, its acylphloroglucinol analogue 8 was more effective.…”