TY - JOUR
T1 - Reinvestigation of structure-activity relationship of methoxylated chalcones as antimalarials
T2 - Synthesis and evaluation of 2,4,5-trimethoxy substituted patterns as lead candidates derived from abundantly available natural β-asarone
AU - Kumar, Rakesh
AU - Mohanakrishnan, Dinesh
AU - Sharma, Abhishek
AU - Kaushik, Naveen Kumar
AU - Kalia, Kalpana
AU - Sinha, Arun Kumar
AU - Sahal, Dinkar
PY - 2010/11
Y1 - 2010/11
N2 - 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 (IC50: 1.8 μM) and 26 (IC50: 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.
AB - 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 (IC50: 1.8 μM) and 26 (IC50: 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.
KW - Antimalarial
KW - Chalcones
KW - Structure-activity relationship
KW - β-Asarone
UR - http://www.scopus.com/inward/record.url?scp=77957832893&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957832893&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2010.08.049
DO - 10.1016/j.ejmech.2010.08.049
M3 - Article
C2 - 20863599
AN - SCOPUS:77957832893
SN - 0223-5234
VL - 45
SP - 5292
EP - 5301
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 11
ER -