TY - JOUR
T1 - Synthesis and bio-evaluation of alkylaminoaryl phenyl cyclopropyl methanones as antitubercular and antimalarial agents
AU - Ajay, Arya
AU - Singh, Vandana
AU - Singh, Shubhra
AU - Pandey, Swaroop
AU - Gunjan, Sarika
AU - Dubey, Divya
AU - Sinha, Sudhir Kumar
AU - Singh, Bhupendra N.
AU - Chaturvedi, Vinita
AU - Tripathi, Renu
AU - Ramchandran, Ravishankar
AU - Tripathi, Rama P.
N1 - Funding Information:
Author thanks, CSIR and DRDO New Delhi for financial assistance. Arya Ajay is thankful to UGC New Delhi for SRF. It is a CDRI communication 7967.
PY - 2010/12/1
Y1 - 2010/12/1
N2 - A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a-6u and 8a-8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d-6h, 6p, 6q and 8a-8c) exhibited good in vitro antitubercular activities with MIC values 3.12-12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a-6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.
AB - A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a-6u and 8a-8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d-6h, 6p, 6q and 8a-8c) exhibited good in vitro antitubercular activities with MIC values 3.12-12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a-6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.
KW - Antimalarial
KW - Antitubercular
KW - Cyclopropylphenyl methanones
KW - FAS-II
KW - Mycobacterium tuberculosis H37Rv
KW - Plasmodium falciparum 3D7
UR - http://www.scopus.com/inward/record.url?scp=78249258717&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2010.09.071
DO - 10.1016/j.bmc.2010.09.071
M3 - Article
C2 - 21041091
AN - SCOPUS:78249258717
SN - 0968-0896
VL - 18
SP - 8289
EP - 8301
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 23
ER -