Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri).
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.
Sen
Rupashree
R
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244 B, Acharya JC Bose Road, Kolkata 700020, India.
Bauri
Ajay Kumar
AK
Chattopadhyay
Subrata
S
Chatterjee
Mitali
M
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D026324:Myristicaceae / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D010936:Plant Extracts; D012118:Resorcinols; C522672:malabaricone A; C522673:malabaricone D; C071788:malabaricone B; C071787:malabaricone C; D000432:Methanol