Reinvestigation of structure-activity relationship of methoxylated chalcones as antimalarials: synthesis and evaluation of 2,4,5-trimethoxy substituted patterns as lead candidates derived from abundantly available natural β-asarone.
We have examined the antimalarial structure-activity relationship of a series of methoxylated chalcones (A-CHCH-CO-B) against Plasmodium falciparum (3D7 strain) using fluorescence-based SYBR Green assay. Our study has revealed that electron releasing methoxy groups on ring A and electron withdrawing groups on ring B increases antimalarial potency while the positional interchange of these groups causes a decrease. In particular, 2,4,5-trimethoxy substitution pattern at ring A provided potent analogues which were easily derived from abundantly available natural β-asarone rich Acorus calamus oil. Cytotoxic evaluation indicated that the most active compounds 27 (IC(50): 1.8 μM) and 26 (IC(50): 2 μM) were also relatively non-toxic. Furthermore, compound 12 showed excellent resistance index of 1.1 against chloroquine resistant Dd2 strain of P. falciparum.
Kumar
Rakesh
R
Natural Plant Products Division, Institute of Himalayan Bioresource Technology (C.S.I.R.), Palampur 176061, H.P., India.
Mohanakrishnan
Dinesh
D
Sharma
Abhishek
A
Kaushik
Naveen Kumar
NK
Kalia
Kalpana
K
Sinha
Arun Kumar
AK
Sahal
Dinkar
D
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000962:Antimalarials; D047188:Chalcones; C012195:asarone