Ngampong KongkathipNarathip PradidpholKomkrit HasitapanRonald GriggWei Chun KaoCarola HunteNicholas FisherAshley J. WarmanGiancarlo A. BiaginiPalangpon KongsaereePitak ChuawongBoonsong KongkathipKasetsart UniversityUniversity of LeedsLiverpool School of Tropical MedicineMahidol University2018-09-242018-09-242010-03-01Journal of Medicinal Chemistry. Vol.53, No.3 (2010), 1211-122115204804002226232-s2.0-77249142352https://repository.li.mahidol.ac.th/handle/123456789/28775Twenty-six novel naphthoquinone aliphatic esters were synthesized by esterification of 1,4-naphthoquinone alcohols with various aliphatic acids. The 1,4-naphthoquinone alcohols were prepared from 1-hydroxy-2-naphthoic acid in nine steps with excellent yields. Twenty-four of the novel synthetic naphthoquinone esters showed significant antimalarial activity with IC 50 values in the range of 0.03-16.63 μM. The length of the aliphatic chain and the presence of C-2′ substituents on the propyl chain affected the activity. Interestingly, compounds 31 and 37 showed very good antimalarial activity and were not toxic to normal Vero cells, and the PTI values of 31 (> 1990.38) and 37 (1825.94) are excellent. Both 31 and 37 showed potent inhibition against P. falciparum 3D7 cyt bc1 and no inhibition on rat cyt bc1. They showed IC50 values in the nanomolar range, providing full inhibition of cyt bc1 with one molecule inhibitor bound per cyt bc1 monomer at the Qo site. © 2010 American Chemical Society.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1021/jm901545z